BT Mice were placed onto a warm stage inside a light-tight camera box with continuous exposure to isoflurane. 4A, ectopic expression of AKR1B10 in MCF-7 increased the cell growth and proliferation compared to the empty vector control, whereas silencing of AKR1B10 in BT-20 cells decreased the cell proliferation. ET Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips. BT 4C). BT /T1_2 1 Tf 0 0 1 rg ET Diacylglycerol (DAG) and subspecies were quantitatively and qualitatively detected by LC-MS through Washington University Mass Spec Facility. Therefore, lipid second messengers are important cellular signal molecules that regulate cell growth, proliferation and survival. Activated ERK1/2 phosphorylates several substrates, including p90RSK and MSK. FOIA Neurons use many different second messengers as intracellular signals. 0 0 m Acetate incorporation into lipid species, including phosphatidylinositol-4,5-bisphosphate (PIP2), inositol-1,4,5- trisphosphate (IP3) and diacylglycerol (DAG), was analyzed by thin layer chromatography (TLC). Therefore, we examined phosphorylation activation of PKC isoforms. J. Biol. /T1_2 1 Tf This fusion protein translocated to phospholipid vesicles in an phosphatidylserine (PS)-dependent manner. *, p<0.05 and **, p<0.01 when compared to vector control. the two second messengers produced by the activity of enzyme Phospholipase C MOG treatment elevated DAG levels up to 4-fold in unstimulated platelets. 10 0 0 10 60 437 Tm Role of the Polyol Pathway in Locomotor Recovery and Wallerian Degeneration after Spinal Cord Contusion Injury. -0.549 0 Td Although repetitive observations were not conducted in these breast cancer cells with targeted expression or silencing of AKR1B10, we believe that the carbonyl detoxification mechanism of AKR1B10 may also contribute to the cell growth and proliferation. We have established a novel role for the second messenger DAG (diacylglycerol), a product of PtdIns(4,5)P2 hydrolysis by PLC . 2022-12-11T18:18:39-08:00 The new PMC design is here! Clipboard, Search History, and several other advanced features are temporarily unavailable. BY, DAMARIS BENNY DANIEL I Msc. <> ET Acad. 10 0 0 10 318 358.99997 Tm DAG activates protein kinase C and IP3 binds to a receptor on the endoplasmic reticulum to release calcium from intracellular stores. An official website of the United States government. 10 0 0 10 318 335 Tm The beta isozymes of PLC are regulated by G-proteins (G-alphaq/11 and G-betagamma) Berridge (1989), Gilman (1989). (B) Levels of various subspecies of DAG in MCF-7 (upper), BT-20 (lower left) and HCT-8 (lower right) cells. Medium was added with 1/10 (v/v) Alamar blue and changed regularly every 24hr. At indicated time points, cells were trypsinized, stained with trypan blue and counted by a Vi-cell counter (Beckman coulter, CA). Castagna, M., Takai, Y., Kaibuchi, K., Sano, K., Kikkawa, U. and Nishizuka, Y. J. Biol. 10 0 0 10 50 389 Tm 121 0 obj Our data showed that ectopic expression of AKR1B10 in breast cancer cells MCF-7 promoted lipogenesis and enhanced levels of lipid second messengers, including phosphatidylinositol bisphosphate (PIP2), diacylglycerol (DAG) and inositol triphosphate (IP3). CrossRef endobj To confirm the cancer-promoting role of AKR1B10, we further evaluated its effects on growth of tumor xenografts in vivo. What is IP3 DAG? As shown in Fig. (A) Inhibition of MCF-7 cell proliferation by MEK inhibitors, PD98059 and U0126 at 10 M or 20 M. Following thrombin stimulation, (/sup 32/P)phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR. Figure 4.. AKR1B10 promotes growth and proliferation. CrossRef ET Our results demonstrated that AKR1B10 increased lipid synthesis, enhanced cellular levels of PIP2, IP3 and DAG, and thus activated the PKC-mediated Raf/MEK/ERK signaling cascade in breast cancer cells. ET Disclaimer, National Library of Medicine /T1_2 1 Tf Viable cells correlate with the magnitude of Alamar blue reduction (%) following the manufactures instructions. <> Martin HJ, Breyer-Pfaff U, Wsol V, Venz S, Block S, Maser E. Purification and characterization of akr1b10 from human liver: role in carbonyl reduction of xenobiotics, Drug metabolism and disposition: the biological fate of chemicals, Aldo-keto reductase family 1 B10 affects fatty acid synthesis by regulating the stability of acetyl-CoA carboxylase-alpha in breast cancer cells, Increased lipogenesis in cancer cells: new players, novel targets, Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis, Overexpression and oncogenic function of aldo-keto reductase family 1B10 (AKR1B10) in pancreatic carcinoma, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. Fukumoto S, Yamauchi N, Moriguchi H /T1_1 1 Tf Lipid extracts and appropriate lipid standards (Sigma, MO) were spotted on silica gel (60; Sigma, MO). A pellet of 17-estradiol (0.72mg/pellet) was implanted beneath the neck skin. In the center, binding of ligands to a GPCR (receptor) activates phospholipase C (PLC; the effector), to generate two second messengers, DAG and IP 3, which activate protein kinase C (PKC; the target) and release calcium from intracellular stores, respectively. endobj 10 0 0 10 60 519 Tm Exp. The high proliferation of cancer cells depends on lipid synthesis to meet both the needs of biomembrane synthesis in cell division and function as signal molecules, stimulating cell growth and proliferation [5]. We further assessed the effect of AKR1B10 on clonogenic growth of MCF-7 cells in three-dimensional (3D) culture in growth factor-reduced extracellular matrix that mimics in vivo environment of mammary epithelial cells. We further explored downstream effectors of the ERK1/2 signaling in MCF-7 cells. 0 1 TD Search terms: Advanced search options. Natl. 194 0 obj BT PI3K phosphorylates phosphatidylinositol bisphosphate (PIP2) to produce phosphatidylinositol (3,4,5)-trisphosphate (PIP3), which activates protein kinase B (PKB, also named AKT); PLC hydrolyzes PIP2 to form inositol triphosphate (IP3) and diacylglycerol (DAG). In contrast, silencing of AKR1B10 in breast cancer cells BT-20 and colon cancer cells HCT-8 led to decrease of these lipid messengers. GFP-labeled cells were sorted for a homogeneous population. Chem. /T1_0 1 Tf Q: A protein contained in red blood cells is . Plating efficiency was calculated as: Colony number/seeded cell number. BT Second Messengers Science 254:17761779, 1991. (Alexandra C. Newton, Martin D. Bootman and John)Tj endobj 562 96 l Interestingly, this study found that aldo-keto reductase 1B10 is a novel regulator of intracellular lipid messengers. and Bell, R.M. 550201* - Biochemistry- Tracer Techniques, - Fed. Earl Wilbur Sutherland Jr . 2022 Feb 24;12:727505. doi: 10.3389/fonc.2022.727505. endobj <>stream This process is experimental and the keywords may be updated as the learning algorithm improves. Oncotarget. 6, MCF-7 tumors with AKR1B10 expression grew faster than vector control tumors. The site is secure. 10/ and PI/sub 10/ was consistently decreased. Additionally, all activators rapidly increased the incorporation of (/sup 3/H)glycerol into DG and, The mechanism of the release of arachidonic acid from phospholipids after the stimulation of guinea pig platelets with collagen, thrombin and platelet activating factor (PAF) was studied. Statistical analyses were performed using Student`s t tests or ANOVA with INSTAT statistical analysis package (Graph Pad software, CA). After packaging in 293T cells, AKR1B10 and empty pCDH lentiviral particles were introduced into cells with standard procedures. (Cell Signaling and Stress Responses)Tj This study showed that AKR1B10 promoted lipogenesis and activated DAG-mediated PKC/ERK signaling cascade. Figure 3.. AKR1B10 activates PKC/ERK signaling pathway. Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. In summary, this study obtained a series of data that mechanistically address the oncogenic role of AKR1B10 in growth and progression of breast cancer. IS, internal standard. 4A At endpoint, we collected tumors and evaluated the phospho-PKC isoforms and phospho-ERK. To verify that the PDGF effect on PA/sub 10/ formation in intact cells was due to reduced phosphorylation of diC/sub 10/ by DAG kinase, cells were treated with PDGF and/or diC/sub 10/, freeze-thawed, and then incubated with Mg(/sup 32/P)ATP. /T1_1 1 Tf about navigating our updated article layout. PMC legacy view The results showed that targeted AKR1B10 expression in MCF-7 cells increased total cellular DAG levels, but oppositely, silencing of AKR1B10 led to decrease of DAG in both BT-20 and HCT-8 cells (Fig. **, p<0.01 when compared to the vector control or PD98059/U0126-treated cells. The colony size of AKR1B10 expression cells was notably larger than that of vector control cells (Fig. Neurotrauma Rep. 2021 Sep 14;2(1):411-423. doi: 10.1089/neur.2021.0018. /T1_1 1 Tf and Hendrickson, W.A. BT /T1_2 1 Tf Correlation analyses were conducted using Spearman correlation and multivariate canonical correlation. (A) Total DAG levels in MCF-7 cells with AKR1B10 expression (left) and BT-20 cells and HCT-8 cells with AKR1B10 silencing (right). The gap of knowledge of AKR1B10 is how the AKR1B10-induced lipogenesis leads to growth and metastasis of breast cancer. In breast cancer cells, AKR1B10 promoted the clonogenic growth and proliferation of breast cancer cells in two-dimension (2D) and three-dimension (3D) cultures and tumor growth in immunodeficient female nude mice through activation of the PKC/ERK pathway. U{7>O5HjQZ_= "\^QR)pxZm.DLXgE\sbg WQp1.0pxz-/(kvek0iKp(&i 6=x18mY^+Bo:sAs \=z18=ORo\pN'66ox+k {{x6S.VfzC>9,vek wn$atB}q^/c?t:?uxEEM:M$I89We^ Rfs5vscZ$V1zdtd>^_{ [7nnYgr\3[cyvD d{pnn>^_|jN$a\5nQpqZQ:*:"18p|gcZSp pU\n+~~9GnhZ<17J JJa`$a!~wRP_\p'O:CbiY|[7nj77z( pGQI'Q'D>;irkai.c{;R A AFF1g\z4x}-fsun;\j. While DAG stays inside the membrane, IP3is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. Western blot results showed that exposure of MCF-7 cells to Go6983 (10 M) abolished phosphorylation activation of ERK1/2 induced by AKR1B10 (Fig. (A) Representative in vivo bioluminescent images at days 3, 10, 20 and 30 post the cell injections. AKR1B10 expression and lipid synthesis in the MCF-7 (A), BT-20 (B) and HCT-8 (C) cells. ET S 10 0 0 10 60 413 Tm 5 and 10 min while PE was able to do so, indicating the failure of AII to provide DAG to sustain protein kinase C activation. S Cells were prelabeled with /sup 32/P and treated with PDGF or carrier. Phospholipid, sphingolipids and sterols are important building blocks of biological membranes. Is glycerol derivative that have two hydroxyl groups esterified by fatty acids. /T1_2 1 Tf They examined effects of concanavalin A and EGF on C-kinase activity and found that both agonists, like insulin, increase C-kinase activity in cytosolic and/or membrane fractions. 562 545 l ET Scrambled and AKR1B10 siRNAs were chemically synthesized (Ambion, TX) and delivered into cells as previously described [37]. DAG and IP 3 are second messengers that can act independently or in unison. /T1_2 1 Tf Mass spectrometry was performed in the Metabolomics Facility at Washington University School of Medicine (P30 DK020579), Campus Box 8086, 660 South Euclid Avenue, St Louis, Missouri 63110. ET With PDGF treatment, the radioactivity in endogenous PA increased fourfold, whereas the radioactivity in PA/sub, Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). 0 g 3Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, and Departments of Oncologic Sciences and Chemistry, University of South Florida, 12902 Magnolia Drive, Tampa, Florida 33612-9416, United States. In these cells, phospho-p90RSK, phospho-MSK and Cyclin D1 expression was increased by AKR1B10, and pharmacological inhibition of the ERK signaling cascade with MEK1/2 inhibitors U0126 and PD98059 eradicated induction of phospho-p90RSK, phospho-MSK and Cyclin D1. Nishinaka T, Miura T, Sakou M, Hidaka C, Sasaoka C, Okamura A, Okamoto A, Terada T. Chem Biol Interact. Herein we found that AKR1B10 activates the cellular lipid second messengers and thus triggers the lipid-mediated cell proliferative signal transduction. ET DAG and IP 3 are second messengers that can act independently or in unison. Their findings raise the possibility that activation of receptors having associated tyrosine kinase activity may provoke some cellular responses through de novo PA/GD synthesis and C-kinase activation. Acrobat Distiller 11.0 (Windows) In: Honn, K.V., Nigam, S., Marnett, L.J. 562 568 l The (http://cshperspectives.cshlp.org/cgi/collection/ )Tj FOIA (Second Messengers)Tj Data processing was conducted with X calibur (Thermo). 10 0 0 10 308 529 Tm 10 0 0 10 308 447 Tm 10 0 0 10 318 437 Tm Learn more 10 0 0 10 60 485 Tm The beta isozymes of PLC are regulated by G-proteins (G-alphaq/11 and G-betagamma) Berridge (1989), Gilman (1989). G-protein coupled receptors (GPCRs) and tyrosine kinase receptors (TKRs) are important upstream activators of lipid second messengers. In breast cancer cells, AKR1B10 promoted the clonogenic growth and proliferation of breast cancer cells in two-dimension (2D) and three-dimension (3D) cultures and tumor growth in immunodeficient female nude mice through activation of the PKC/ERK pathway. endstream Aldo-keto reductase 1B10 (AKR1B10), also referred as aldose reductase-like-1 (ARL-1) [11], is a monomeric enzyme with strong catalytic activity to , -unsaturated carbonyl compounds [12-14] and protects the host cells from carbonyl lesions [15-17]. The .gov means its official. Relative quantification of lipids was provided, and data were reported as the peak area ratios of the analytes to the internal standard. (Mary B. Kennedy)Tj 10 0 0 10 50 471 Tm 148 0 obj 10 0 0 10 242.84967 212 Tm Biol. endobj ERK1/2 also induces cyclin D1 expression through an AP-1 mediated mechanism, stimulating G1/S progression and cell proliferation [10,40]. *, p<0.05 and **, p<0.01 when compared to vector control. Chem. ET AKR1B10 promotes lipogenesis and enhances cellular PIP2, DAG and IP3 levels. ERK1/2 can phosphorylate T369 and T573 residues of p90RSK to enhance cell survival signals [10,39]. We used the LC-Mass Core facility of Washington University at St Louis to quantitatively measure total DAG and 16 subspecies in cells with targeted expression or silencing of AKR1B10 (Supplemental Figure S1). 6/21/2016by Yonas Teshome 4 R and R' are saturated or unsaturated hydrocarbon chains. U.S.A. 86:83238327, 1989. Quality control (QC) samples were prepared by pooling the aliquots of study samples and were used to monitor instrument stability. to target molecules in the cytosol and/or nucleus. /T1_1 1 Tf 10 0 0 10 318 403 Tm BT )Tj We next tested if the ERK1/2 signaling activation is responsible for increased cell proliferation by AKR1B10. Neurosci. <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/Rotate 0/Type/Page>> 3-phosphoinositide-dependent protein kinase-1 regulates proliferation and survival of cancer cells with an activated mitogen-activated protein kinase pathway, Sustained MAP kinase activation is required for the expression of cyclin D1, p21Cip1 and a subset of AP-1 proteins in CCL39 cells. (B) Raf/MER/ERK activation by AKR1B10, showing p-Raf, p-MEK and p-ERK1/2 levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling. The glycerol is linked with the fatty acid chain through ester linkages. Introduction Diacylglycerol (DAG) is a lipid signal messenger which is an essential second messenger in mammalian cells. 280:233241, 1991. (Ivana Y. Kuo and Barbara E. Ehrlich)Tj 267:1019310197, 1992. National Library of Medicine **, p<0.01 when compared to AKR1B10 Control cells. Chem 261:93419347, 1986. Europe PMC is an archive of life sciences journal literature. Lipid samples and standards were visualized by coloration in staining solution (0.12 M NaCl, 20% methanol, and 300 mg/liter Coomassie Blue). A: We can say that Hormones can be described as the chemical secreted by specialized cells of endocrine. This appears to be due to the inability of these platelets to metabolize agonist-linked DAG via the lipase pathway. ET (G\366khan S. Hotamisligil and Roger J. Davis)Tj Dag Second Messengers: Molecular Switches and Growth Control. ET (Subversion of Cell Signaling by Pathogens)Tj 4A AKR1B10 expression and lipid synthesis in the MCF-7 (A), BT-20 (B) and HCT-8 (C) cells. RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. 10 0 0 10 60 335 Tm The second messenger pathway which concerns the intracellular action of Ca2+ ions is involved in a variety of actions that include the collaboration with DAG for the activation of PKC and the calcium-modulated protein (calmodulin or Cam) kinase pathway. 0 0 m Cells (4000/well) were seeded. Figure 6.. AKR1B10 promotes tumor growth in female nude mice. Yan R, Zu X, Ma J, Liu Z, Adeyanju M, Cao D. Aldo-keto reductase family 1 B10 gene silencing results in growth inhibition of colorectal cancer cells: Implication for cancer intervention, Separation of phosphatidylinositols and other phospholipids by two-step one-dimensional thin-layer chromatography. et al. BT 1B). DAG activates protein kinase C and IP 3 binds to a receptor on the endoplasmic reticulum to release calcium from intracellular stores. **, p<0.01 when compared to the vector control or PD98059/U0126-treated cells. Right panel: Quantitative analyses of indicated proteins. In many cases the response of the cell membrane is the production of small rapidly diffusible "second messenger" substances inside the cell. Similar to other. In contrast, phosphorylation of these PKC isoforms decreased in BT-20 cells with AKR1B10 silencing by two different siRNAs that target different regions of mRNA. BT endobj left) and cell number counting (Fig. The results showed that AKR1B10 expression and resulting activation of the MEK/ERK signaling increased the phosphorylation of p90RSK and MSK and cyclin D1 expression; and the MEK1/2 inhibitor U0126 abolished the p90RSK and MSK phosphorylation and cyclin D1 expression stimulated by AKR1B10 (Fig. This finding suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. Mol. 2018 Oct; 57(10): 13001310. Signal transduction in vascular smooth muscle: diacylglycerol second messengers and PKC action. ET 1C). Metabotropic signaling with G-protein coupling. [251 0 R 252 0 R 253 0 R 254 0 R] ET BT DAG has a great role in biochemical signaling. Natl. BT 5. 4China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin, 541001, Guangxi, China. HHS Vulnerability Disclosure, Help application/pdf In contrast, silencing of AKR1B10 in breast cancer cells BT-20 and colon cancer cells HCT-8 led to decrease of these lipid messengers. Conflict of interest: Authors declare no conflict of interest with the contents of this article. Chem. 468 0 0 60 72 126 cm (Sally Kornbluth and Rafael Fissore)Tj and PAF increased phospholipase C activity. Fatty acids are essential components of various lipids, such as triglycerides and phosphoglycerides. T* Briefly, MCF-7 cells (3,000 cells/well) were plated in 96-well plates. These results define an oncogenic role of AKR1B10 in growth and progression of breast cancer and clarify the mechanisms of action. luciferase substrate D-luciferin at 100 mg/kg in PBS and anesthetized by isoflurane. By catalysis of phospholipase C (PLC), PIP2 is hydrolyzed into DAG and IP3 [9]. Before Epub 2006 May 6. AKR1B10 increases fatty acid synthesis by stabilizing ACCA, enhancing cellular phospholipids and sterols. uuid:79068d31-c36f-4e54-9b1e-32efcd71848f 2021 Nov 13;20(1):160. doi: 10.1186/s12944-021-01572-z. IP3 diffuses freely into cytoplasm, triggering endoplasmic reticulum (ER)-mediated Ca2+ signaling; DAG remains in cell membrane and activates protein kinase C (PKC) [5-7]. *, p<0.05 and **, p<0.01 when compared to vector control. 10 0 0 10 413.50934 345 Tm Qualitative analyses by liquid chromatography-mass spectrum (LC-MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. Therefore, it seemed that endogenous DAGs, derived from PI, might be better substrates for DAG kinase than is diC/sub 10/. Luciferase-labelled MCF-7 cells with targeted AKR1B10 expression or a vector control were injected subcutaneously into the mammary fat pads of female nude mice (n=5 per group). Second messengers. Increased PIP2 and IP3 levels in breast cancer cells encouraged an extended study on DAG and the DAG-mediated signaling transduction. ET BT This result was confirmed by both Alamar blue (Fig. 10 0 0 10 318 311 Tm BT official website and that any information you provide is encrypted (Post-Genomic Era)Tj -19.28497 0 Td Sci. <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/Rotate 0/Type/Page>> ET Briefly, after being washed with PBS, cells were harvested by trypsinization and suspended in 40 l of PBS. /T1_2 1 Tf ET (A) Total DAG levels in MCF-7 cells with AKR1B10 expression (left) and BT-20 cells and HCT-8 cells with AKR1B10 silencing (right). 10 0 0 10 318 461 Tm ACCA is a rate-limiting enzyme in de novo fatty acid synthesis, and thus AKR1B10 drives biosynthesis of long chain fatty acids [26]. 0 0 1 rg See this image and copyright information in PMC. (1997). Author contributions: CH and ZC were involved in experimental studies and data analysis and CH also participated in discussion, wrote the draft and prepared Figures. (A) Proliferation of MCF-7 and BT-20 cells measured by Alamar blue assays (left) and cell counting assays (right). PMC (C) ERK inhibition by a broad PKC inhibitor, Go6893 (10M), showing decreased p-ERK1/2 level by Go6893 in the MCF-7 cells with AKR1B10 expression. This is a preview of subscription content, access via your institution. Accessibility Sun Y, Liu WZ, Liu T, Feng X, Yang N, Zhou HF. https://doi.org/10.1007/978-1-4615-5325-0_42, DOI: https://doi.org/10.1007/978-1-4615-5325-0_42. 0 g 10 0 0 10 50 495 Tm BT Various in vitro assays for enzymes involved in arachidonic acid release and metabolism were conducted. Acini were photographed by a phase contrast microscopy (Carl Zeiss, CA). The https:// ensures that you are connecting to the Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. Zeman RJ, Wen X, Ouyang N, Brown AM, Etlinger JD. J. Biol. -8.11398 0 Td (Signaling Networks: Information Flow,)Tj 9:39073912, 1990. BT Please enable it to take advantage of the complete set of features! *, p<0.05 and **, p<0.01 when compared to AKR1B10 Control cells. 0 0 1 rg and Bell, R.M. AKR1B10 is an oncoprotein that promotes growth and progression of breast cancer. (A) PKC activation by AKR1B10, showing p-PKC (Thr505), p-PKC (Ser744/748) and p-PKC/II (Thr638/641) levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced (/sup 32/P)phosphatidic acid formation in SHR. /T1_1 1 Tf /T1_1 1 Tf AII (5 x 10/sup -7/M) causes only a transient contractile response, while PE (10/sup -5/M) causes a sustained tonic contraction. Am J Physiol. 2 0 obj It functions as a second messenger that facilitates the protein kinase C (PKC) enzyme's movement from the . Imaging times were controlled equally at 15 sec, and signal quantification was performed by an acquisition and analysis software (Living ImageVR, Xenogen, CA) and expressed as amount of Flux (photons per second). phosphatidylinositol (3,4,5)-trisphosphate. Revealing potential lipid biomarkers in clear cell renal cell carcinoma using targeted quantitative lipidomics. (b)Tj Proc., Fed. A pan inhibitor of PKC (Go6983) blocked ERK1/2 activation by AKR1B10. Mol Carcinog. 3C). DC and JJ worked in all aspects of the project and revised the manuscript. (B) Plating efficiency of MCF-7 cells in cell culture dishes. Kolch, W., Heidecker, G., Lloyd, P. and Rapp, U. 7). Leach, K.L., Ruff, V.A., Wright, T.M., Pessin, M.S. These keywords were added by machine and not by the authors. /T1_1 1 Tf Federal government websites often end in .gov or .mil. BT T* MeSH In unstimulated cells, both the rate and extent of /sup 32/P incorporation into individual inositol-containing phospholipids and phosphatidic acid were identical in SHR and WKY. (1994) The Regulatory domain of protein kinase C gamma: studies of phorbol ester binding to individual and combined functional segments expressed as GST-fusion proteins indicate a complex mechanism of regulation by phospholipids, phorbol esters and divalent cations (Submitted), Ghosh, S., Xie, W.Q., Quest, A.F.G., Malbrouk, G.M., Strum, J.C. and Bell, R.M. Cell suspensions (50 ml/inoculation) were subcutaneously injected with a 25-gauge needle into mammary fat pads of female nude mice at 5 weeks old. 2021 Aug 21;11(1):163. doi: 10.1186/s13578-021-00677-3. Arbortext Advanced Print Publisher 9.1.520/W /Im0 Do Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. Am. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Therefore, AKR1B10 may activate lipid second messenger-mediated signaling cascades to affect growth and proliferation of breast cancer cells. <> For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more (/sup 32/P)phosphatidic acid in SHR than in WKY. We further confirmed the activation of ERK1/2 signaling by PKC using a broad PKC inhibitor, Go6983. Diacylglycerol (DAG) is composed of two chains of fatty acids that are in a covalent bond with a molecule of glycerol. As shown in Fig. This site needs JavaScript to work properly. (Signals and Receptors)Tj However, little is known of the molecular mechanisms of action. 8:138153, 1993. 189 0 obj Cancer cells preferentially use the newly synthesized fatty acids for phospholipid synthesis and biomembrane construction [27,28]. 15 0 0 15 50 624 Tm *, p<0.05 and **, p<0.01 when compared to vector control. The development of specific inhibitors of DAG kinase and DAG lipase, in conjunction with mass quantification of DAG levels as used here, will providemore further insights into the regulation of DAG second messengers.less, The authors have reported that insulin stimulates de novo synthesis of phosphatidic acid (PA) which is metabolized directly to diacylglycerol (DG) in BS3H-1 myocytes; this is accompanied by increases in C-kinase activity in membrane and cytosolic extracts. ET (Kian-Huat Lim and Louis M. Staudt)Tj S As shown in Figure 6D, the PKC/ERK signaling pathway was activated by AKR1B10 in tumors. 10 0 0 10 50 554 Tm Lipid fractions were re-suspended into 50% methanol solution, and radioactivity were measured by scintillation counter (Beckman Instruments). But in addition to their job as relay molecules, second messengers serve to greatly amplify the strength of the signal. Tel: (314) 747-0677. /T1_1 1 Tf BT /T1_0 1 Tf Advances in Experimental Medicine and Biology, vol 400. 10 0 0 10 50 447 Tm and transmitted securely. ET Tumor volume was monitored by both in vivo imaging and caliper measurements. ET Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. Keywords: The levels of second messengers are exquisitely. doi: 10.1152/ajpcell.1994.267.3.C659. Significance was defined as p<0.05. By contrast, although the COOH-terminal conserved C-151 was involved in the coordination of 1 zinc atom, it was not essential for PDBu binding. 1Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine. T* 10 0 0 10 308 471 Tm (\240)Tj eCollection 2021. Full-length AKR1B10 cDNA was inserted into pCDH lentiviral expression vector with a GFP reporter (System Biosciences, CA). 10 0 0 10 308 412.99997 Tm J. ZOOLOGY 2. AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-B signaling pathway. Under these conditions the DAG signal was somewhat long-lived but was still metabolized, presumably by the lipase pathway. BT Department of Molecular Cancer Biology, Duke University Medical Center, Durham, NC, 27710, USA, Andrew F.G. Quest,Sujoy Ghosh,Wen Qin Xie&Robert M. Bell, You can also search for this author in CAS 8600 Rockville Pike (B) ERK targeted genes in MCF-7 cell. PubMed government site. Feig, L.A. and Cooper, G.M. 1997;400A:297-303. doi: 10.1007/978-1-4615-5325-0_42. /T1_2 1 Tf More importantly, membrane phospholipids are a major group of lipid second messengers, mediating cellular signaling pathways of cancer cell growth and proliferation [1]. sharing sensitive information, make sure youre on a federal will also be available for a limited time. These data suggest that AKR1B10 promotes breast cancer growth in vivo by activating the PKC/ERK signaling pathway, being an oncogenic protein in breast cancer growth and progression. These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG-mediated PKC/ERK signaling pathway. ET /T1_1 1 Tf (Copyright \251 2016 Cold Spring Harbor Laboratory Press; all rights rese\ rved)Tj ET and Bell, R.M. Before (B) Plating efficiency of MCF-7 cells in cell culture dishes. ET In these cells, phospho-p90RSK, phospho-MSK, and Cyclin D1 expression was increased by AKR1B10, and pharmacological inhibition of the ERK signaling cascade with MEK1/2 inhibitors U0126 and PD98059 eradicated induction of phospho-p90RSK, phospho-MSK, and Cyclin D1. Conflict of interest: Authors declare no conflict of interest with the contents of this article. J. Biol. and Bell, R.M. <> The 3D culture was done in growth factor-reduced Matrigel (BD Biosciences, CA) [36]. (Douglas R. Green and Fabien Llambi)Tj These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG-mediated PKC/ERK signaling pathway. Left panel: Quantitative analysis of band intensity. Biologically, AKR1B10 promotes fatty acid/lipid synthesis. Li J, Guo Y, Duan L, Hu X, Zhang X, Hu J, Huang L, He R, Hu Z, Luo W, Tan T, Huang R, Liao D, Zhu YS, Luo DX. BT (Cold Spring Harb Perspect Biol\240)Tj -14.28398 0 Td However, little is known of the molecular mechanisms of action. ET (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2. Protein kinase C isozymes are stereospecifically regulated by diacylglycerol (DAG) second messengers or phorbol esters (PDBu) through interactions with cysteine-rich PKC segments (Cysl, Cys2) containing six conserved cysteines (C) and two conserved histidines (H) in the pattern H-X12-C-X1014-C-X2-C-X4-H-X2-C-X7-C where X are non-conserved residues. AKR1B10 promotes biosynthesis of long chain fatty acids by stabilizing ACCA [26]. Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2 pp 297303Cite as, Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 400). PDBu binding was decreased substantially upon removal of Val147 and lost entirely when Val144 was deleted. For 2D culture, cells were seeded at 200 cells per 60-mm culture dish and incubated in indicated medium for 14 days; colonies were fixed by methanol (cooled at 20C) for 10 min and visualized by 0.1% crystal violet. Second messengers are typically present at low concentrations in resting cells and can be rapidly produced or released when cells are stimulated. 300 0 0 75 156 657 cm BT Hydrolysis by PLC, PIP2 is broken down into DAG and IP3. ET Measurement of DAGs were performed with a Shimadzu 10A HPLC system and a Shimadzu SIL-20AC HT auto-sampler coupled to a Thermo Scientific TSQ Quantum Ultra triple quadrupole mass spectrometer operated in SRM mode under ESI(+). They are a component of cell signaling pathways. endobj Second messenger system 1. sharing sensitive information, make sure youre on a federal Growth rate of cells was measured using Alamar blue (ABD Serotec, UK) reduction assay. (Second Messengers)Tj 0 1 TD Y axis is in log10. In brief, lipids were extracted from 5106 cells using a modified Bligh-Dyer method in the presence of an internal standard DG15:0-15:0 (0.5 g per sample). This study showed that AKR1B10 promoted clonogenic growth of breast cancer cells by increasing lipogenesis and thus activating lipid second messengers PIP2 and DAG-mediated PKC/ERK signaling cascade. 50 96 m (Carl-Henrik Heldin, Benson Lu, Ron Evans, et al. In the breast cancer cells, AKR1B10 promotes lipogenesis and increases cellular lipid second messengers PIP2, IP3 and DAG, which activates the PKC/ERK signaling cascade. PDGF treatment caused an increase in DAG mass, an increase in incorporation of /sup 32/P into phosphatidic acid (PA) and phosphatidylinositol (PI), and an increase in the rate of phosphorylation of membrane DAG in vitro. endstream CAS BT -10.00193 0 Td PMID: 9547571 DOI: 10.1007/978-1-4615-5325-0_42 Careers. and Bell, R.M. (Alexandra C. Newton, Martin D. Bootman and John D. Scott)Tj 2006 Jun;27(6):317-23. doi: 10.1016/j.tips.2006.04.003. Figure 7.. Hypothetic model of cell growth. Figure 5.. ERK signaling and target genes, Figure 5.. ERK signaling and target genes that are involved in cell proliferation enhanced by, Figure 6.. AKR1B10 promotes tumor growth in. BT DAG and subspecies were measured quantitatively by liquid chromatography-mass spectrum as described in Methods and Materials. (A) PKC activation by AKR1B10, showing p-PKC (Thr505), p-PKC (Ser744/748) and p-PKC/II (Thr638/641) levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. The ability of AII and phenylephrine (PE) to induce diacylglycerol (DAG) production was monitored as agonist-stimulated /sup 32/P-labelling of phosphatidic acid (PA). U.S. Department of Energy Office of Scientific and Technical Information. <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/Rotate 0/Type/Page>> Scram, scrambled siRNA; SiR-1, AKR1B10 siRNA-1; and SiR-2, AKR1B10 siRNA-2. Quest, A.F.G., Bardes, E.S.G., Bloomenthal, J.B., Borchardt, R.A. and Bell, R.M. (\240)Tj (1994a) J. Biol. . ET /T1_2 1 Tf (Subject Collection)Tj This in turn modulated the phosphorylation of protein kinase C (PKC) isoforms PKC (Thr505), PKC (Ser744/748) and PKC/II (Thr638/641) and activity of the PKC-mediated c-Raf/MEK/ERK signaling cascade. and Stacey, D.W. 10 0 0 10 60 311 Tm (Jeremy Thorner, Tony Hunter, Lewis C. Cantley, et)Tj 226 0 obj 244 0 obj 1994 Sep;267(3 Pt 1):C659-78. BT Quest, A.F.G., Bioomenthal, J.B., Bardes, E.S.G. Long chain fatty acids are important components of membrane phospholipids and lipid second messengers which mediate cellular signaling transduction and thus cell survival and proliferation [5-7]. Diacylglycerol (DAG) and subspecies were quantitatively and qualitatively detected by LC-MS through Washington University Mass Spec Facility. /T1_2 1 Tf Acad. (A) Proliferation of MCF-7 and BT-20 cells measured by Alamar blue assays (left) and cell counting assays (right). /T1_3 1 Tf /T1_1 1 Tf ; (United States). More importantly, AKR1B10 is a mediator of long chain fatty acid synthesis. (B) Tumor volumes by in vivo bioluminescence at photon/second. Such raf-1 translocation to the membrane brings it in proximity to activated GTP-ras which interacts directly with raf-1 during signal transduction. Cell Death Discov. 10 0 0 10 50 321 Tm In Press. 0 g <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/Rotate 0/Type/Page>> (B) ERK targeted genes in MCF-7 cell. 10 0 0 10 308 378.99997 Tm ( Superfamily)Tj A: Joints can be outlined as the point where two parts of the skeletal system are associated with each . 137 0 obj Google Scholar. BT 10 0 0 10 318 485 Tm BT Part of Springer Nature. This study addressed the gap of AKR1B10 knowledge and dissected the signaling pathways, through which AKR1B10 stimulates the growth and proliferation of breast cancer cells. (Toll-Like Receptor Signaling)Tj Science 238:17261728, 1987. AKR1B10 also mediates cancer cell sensitivity to anthracyclines [24,25]. The rate of phosphorylation of cell-associated diC/sub 10/ was decreased 50% by PDGF treatment. Diacylglycerol(DAG) derived from phosphatidylinositol activates protein kinase C in agonist-stimulated cells. Cells were pulsed with 1Ci of [2-14C] acetate (53 mCi/mmol; Amersham Biosciences) per well of 12-well plates for 4h at 37 C, 5% CO2 in complete medium. Together these data suggest that AKR1B10 promotes clonogenic growth and proliferation of breast cancer cells. PKD at the crossroads of DAG and PKC signaling. (D. Scott)Tj In breast cancer cells, the activated ERK signaling by AKR1B10 enhanced cell growth and proliferation through phosphorylation activation of p90RSK and MSK and expression of cyclin D1, and this was proven by pharmacological inhibition of ERK1/2 activity using MEK1/2 inhibitors U0126 and PD98059. In vivo studies in immunodeficient female nude mice confirmed the tumor-promoting role of AKR1B10 in breast cancer. Indomethacin completely inhibited collagen-induced platelet aggregation, was less effective against thrombin, and had no effect on PAF-induced platelet aggregation. /T1_2 1 Tf (Michael J. Lee and Michael B. Yaffe)Tj Qualitative analyses by liquid chromatography-mass spectrum (LC-MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. Very recently, we found that AKR1B10 stimulates metastasis of breast cancer through integrin 5/-catenin mediated FAK/Src/Rac1 signaling pathway [33]. Briefly, mice were given (i.p.) (Neal M. Alto and Kim Orth)Tj ET AKR1B10 is upregulated in human breast cancer and correlates with tumor size and lymph node metastasis [31], but the underlying molecular mechanisms are unclear. Bookshelf Wang C, Yan R, Luo D, Watabe K, Liao DF, Cao D. Aldo-keto reductase family 1 member B10 promotes cell survival by regulating lipid synthesis and eliminating carbonyls, Aldo-keto reductase 1B10 protects human colon cells from DNA damage induced by electrophilic carbonyl compounds. 2B). (B) Raf/MER/ERK activation by AKR1B10, showing p-Raf, p-MEK and p-ERK1/2 levels in the MCF-7 with ectopic expression of AKR1B10 and BT-20 cells with silencing of AKR1B10. 265:14, 1990. and transmitted securely. endobj It is noteworthy to note that AKR1B10 can promote cell survival through protection from reactive carbonyl lesions [13,17,37]. ET 0 0 m AKR1B10 is not expressed in normal breast, but up-regulated in breast cancer, indicating a poor prognosis. /T1_2 1 Tf uuid:b03733e8-1dd1-11b2-0a00-aa00a8a7ebff Proc. BT After being air-dried, plates were developed in hexane/diethyl ether/acetic acid (70/30/1, v/v) to separate neutral lipids, such as DAG, or in chloroform/methanol/acetic acid (65/25/10, v/v) to separate phospholipids, such as PIP2 and IP3. This pathway may be involved in stimulating glucose transport and other metabolic processes. However, little is known of the molecular mechanisms of action. GST-fusion proteins containing this region of raf-1 contained two moles of zinc but did not bind PDBu. USA 83:11841188, 1986. 257:78477851, 1982. Hannun, Y. and Bell, R.M. AKR1B10 knockdown was examined using Western blot. /T1_1 1 Tf BT ET Accessibility DAG activates important oncogenic signaling molecule PKC, and IP3 provokes ER-mediated calcium signaling, further activating PKC. Only the lipid species with CV < 15% in QC sample were reported. -1 TL /Im1 Do (Signaling in Muscle Contraction)Tj An aliquot (10 l) of the cell suspension was used for protein quantitation, and the remainder was mixed vigorously with 20 volumes of chloroform/ methanol (2:1, v/v). In 2D plating efficiency assays, the colony formation rate of MCF-7 cells with AKR1B10 expression was at an average of 78.04.8% (n=3), compared to 56.01.6% in the vector control cells. Figure 7.. Hypothetic model of cell growth and proliferation promoted by AKR1B10. /T1_1 1 Tf 2Division of Stem Cell Regulation and Application, State Key Laboratory of Chinese Medicine Powder and Medicine Innovation in Hunan (incubation), Hunan University of Chinese Medicine, Changsha, Hunan 410208, China. More impressively, AKR1B10 promoted clonogenic growth of MCF-7 cells, a feature of cancer cells. Quest, A.F.G., Bardes, E.S.G. 191 0 obj In brief, lipids were extracted from 510 6 cells using a modified Bligh-Dyer method in the presence of an internal standard DG15:0-15:0 (0.5 g per sample). Figure 1.. AKR1B10 promotes lipogenesis of cancer cells. Figure 2.. AKR1B10 increases DAG levels in breast cancer cells. /T1_2 1 Tf *, p<0.05 and **, p<0.01 when compared to vector control. T* We thus assessed the effect of targeted AKR1B10 expression on growth and proliferation of breast cancer cells. After incubation on ice for 10 min, debris was removed at 21,000 xg for 10 min, and the supernatant was washed with 0.2 volume of distilled water. %PDF-1.4 % second messenger, molecule inside cells that acts to transmit signals from a receptor to a target. DiC/sub 10/ was added to the cell medium before harvesting. AKR1B10 expression and lipid synthesis in the, Figure 2.. AKR1B10 increases DAG levels in. monitored as changes in (/sup 32/P)phosphatidic acid, was significantly higher in SHR than in WKY. Increased lipogenesis is an essential feature of cancer cells to meet the needs of phospholipids for biomembrane synthesis and cell division. Two analogs were potent inhibitors in vitro, 1-monooleoylglycerol(MOG,K/sub I/ = 91 ..mu..M) and diotanoylethyleneglycol (diC/sub 8/EG, K/sub I/ = 58 ..mu..M). A pan inhibitor of PKC (Go6983) blocked ERK1/2 activation by AKR1B10. cAMP, cGMP, IP3, DAG. Proc. -8.83699 0 Td Therefore, AKR1B10-induced lipogenesis may have critical impact in cancer development and progression. 2022 Springer Nature Switzerland AG. /T1_2 1 Tf Y axis is in log10. 50 545 m Lipids are a group of water-insoluble intracellular molecules, such as phosphoglycerides, triglycerides, sphingolipids and sterols. /T1_0 1 Tf (2016; doi: 10.1101/cshperspect.a005926)Tj Zu X, Yan R, Robbins S, Krishack PA, Liao DF, Cao D. Reduced 293T cell susceptibility to acrolein due to aldose reductase-like-1 protein expression, Toxicological sciences : an official journal of the Society of Toxicology, Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer, Oxidative medicine and cellular longevity, Development of a 32P-postlabelling method for the detection of 1,N2-propanodeoxyguanosine adducts of crotonaldehyde in vivo, Microbially produced acetaldehyde from ethanol may increase the risk of colon cancer via folate deficiency, International journal of cancer Journal international du cancer, Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10, Proceedings of the National Academy of Sciences of the United States of America, Aldo-keto reductases from the AKR1B subfamily: retinoid specificity and control of cellular retinoic acid levels, AKR1B10 induces cell resistance to daunorubicin and idarubicin by reducing C13 ketonic group. The pathway begins with the binding of extracellular primary messengers such as epinephrine, acetylcholine, and hormones AGT, GnRH, GHRH, oxytocin, and TRH, to their respective receptors. By targeted expression in MCF-7 cells, we examined cellular lipids, and our results showed that AKR1B10 significantly enhanced the levels of total lipids and lipid second messengers, phosphatidylinositol 4,5-bisphosphate (PIP2) and inositol 1,4,5-trisphosphate (IP3) (Fig. DAG second messengers: molecular switches and growth control Adv Exp Med Biol. Our data showed that ectopic expression of AKR1B10 in breast cancer cells . <>/Filter/FlateDecode/Height 300/Length 34147/Name/X/Subtype/Image/Type/XObject/Width 1200>>stream Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas, Clinical cancer research : an official journal of the American Association for Cancer Research, AKR1B10 overexpression in breast cancer: association with tumor size, lymph node metastasis and patient survival and its potential as a novel serum marker, Epidermal growth factor induces tumour marker AKR1B10 expression through activator protein-1 signalling in hepatocellular carcinoma cells, AKR1B10 promotes breast cancer metastasis through integrin alpha5/delta-catenin mediated FAK/Src/Rac1 signaling pathway. (Protein Regulation in Signal Transduction)Tj ET Relative quantification data generated in same batches are appropriate to compare the change of an analyte in AKR1B10 expression or AKR1B10 silencing samples to the corresponding control. DAG is an activator of protein kinase C (PKC) family members [9]. Biol. These data suggest that AKR1B10 participates in regulation of lipid second messengers in breast cancer cells. 10 0 0 10 308 495 Tm PubMed Figure 1.. AKR1B10 promotes lipogenesis of cancer. 8600 Rockville Pike /T1_2 1 Tf )Tj 4. The DAG formed was in a pool where it did not activate protein kinase C. Thrombin-stimulation of MOG-treated platelets resulted in DAG levels 10-fold higher than control platelets. <>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Type/Page>> Two siRNAs that target encoding (siRNA 1: 5` GCAAGUUGUGGCCCACUUUtt) and 3` untranslational (siRNA 2: 5` CGAGAAUCGAGGUGCUGUUtt) regions of AKR1B10 were used for silencing. The guinea pig platelet is an ideal model to study phospholipase C-diacylglycerol lipase pathway for the release of arachidonic acid from platelet phospholipids because it does not have any phospholipase A/sub 2/ activity. /T1_1 1 Tf Increased incorporation into phospholipids and triacylglycerols and to a lesser extent monoacylglycerol was also noted. (A) Mechanisms responsible for producing and removing second . A scrambled siRNA with random RNA sequences was used as a control. The p-ERK1/2, p-p90RSK and p-MSK levels and Cyclin D1 expression were increased by AKR1B10 in the cells, and the increased p-p90RSK, p-MSK and Cyclin D1 levels were eradicated by MEK inhibitor, U0126 (10 M). 3A, AKR1B10 expression in MCF-7 cells enhanced the level of phosphorylated PKC (Thr505), PKC (Ser744/748) and PKC/II (Thr638/641). /T1_2 1 Tf As shown in Fig. The DAG pathway is a message generating pathway that is involved in the activation of enzymes and in turn produces various biological events, including transcription of DNA. Analytical data of DAG subspecies demonstrated that targeted expression of AKR1B10 markedly increased the levels of majority of 16 DAG subspecies, but AKR1B10 silencing led to decrease of DAG subspecies (Fig. In contrast, early thrombin-induced phosphoinositide metabolism, when, A possible role for protein kinase C during the tonic phase of arterial contraction was examined in rat aorta by observing the effects of the phorbol ester, 12-0-tetradecanoylphorbol-13-acetate (TPA), on angiotensin II (AII)-induced responses. All were found to be effective in stimulating glucose transport. Lu Z, Cox-Hipkin MA, Windsor WT, Boyapati A. /T1_2 1 Tf (al. /T1_0 1 Tf Tumor volume was measured using in vivo bioluminescent imaging with an IVIS VR imaging system (Xenogen, CA) and also measured by Vernier caliper. An official website of the United States government. 1A). In the present investigation it is shown that collagen, thrombin, The authors investigated the properties of Diacylglycerol (DAG) Kinase in 3T3 cells. 130 0 obj further insights into the regulation of DAG second messengers. BT Sci. Careers, The publisher's final edited version of this article is available at, GUID:E2FCDCBA-1036-4140-99CD-716FC3170795, AKR1B10, breast cancer, lipid second messengers, phosphatidylinositol bisphosphate, diacylglycerol, PKC/ERK cascade, Cancer Metabolism: A Modeling Perspective, Signal transduction through lipid second messengers. In fact, AKR1B10 is upregulated in multiple solid cancers, such as liver, breast, lung and pancreatic cancers, being a potential prognostic biomarker [29-32]. These results are in consistence with clinical settings that AKR1B10 expression in breast cancer correlates with tumor size and worse disease-free survival [31]. CAS Ahmed, S., Kozma, R., Lee, J., Monfries, C., Harden, N. and Louis, L. Biochem. IP 3, DAG, and Ca 2+ are second messengers in the phosphoinositol pathway. LncRNA 1700020I14Rik promotes AKR1B10 expression and activates Erk pathway to induce hepatocyte damage in alcoholic hepatitis. The minimal sequence required for PDBu binding was elucidated by deletion analysis. AKR1B10 promotes breast cancer metastasis through integrin 5/-catenin mediated FAK/Src/Rac1 signaling pathway. The CYS2 region of PKC-gamma (amino acids 92173) expressed as a COOH-terminal fusion protein with glutathione-S-transferase (GST-Cys2) displayed high-affinity, stereospecific, and phospholipid dependent binding to phorbol ester and contained 2 moles of zinc per mole protein. (Vertebrate Reproduction)Tj government site. AKR1B10 as a Potential Novel Serum Biomarker for Breast Cancer: A Pilot Study. Second Messengers Often the extracellular message is a chemical (hormone or neurotransmitter), which binds to its receptor on the cell membrane, which in turn triggers events in the membrane. Ganong, B.R., Loomis, C.R., Hannun, Y.A. Download preview PDF. Soc. At least two pathways may contribute to the attenuation of the DAG signal: (1) phosphorylation to phosphatidic acid(PA) by DAG kinase(DGK), and (2) deacylation by DAG and monoacylglycerol lipases. BT (Jeffrey L. Wrana)Tj In normal tissues, AKR1B10 is primarily expressed in the colon and small intestine [11,34], where it regulates proliferation and self-renewal of cryptic epithelial cells [35]. Download full-text PDF Read full-text. BT The .gov means its official. BT endobj Nature 320:540543, 1986. primary messenger binds to receptor and generates second messenger in 2 ways: 1) by opening ion channels and this will lead to influx of some ions. 2) by activation of enzyme in cell membrane. ET <>stream Down-regulation of aldo-keto reductase AKR1B10 gene expression by a phorbol ester via the ERK/c-Jun signaling pathway. 8 0 0 8 260.42407 754 Tm Chem. 122 0 obj A.C. Newton et al. They greatly amplify the strength of the signal, cause some kind of change in the activity of the cell. /T1_1 1 Tf Trends Pharmacol Sci. ET q Download full-text PDF. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis, Journal of receptor and signal transduction research. Cell. Authors A F Quest 1 , S Ghosh , W Q Xie , R M Bell Affiliation 1 Department of Molecular Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. Li W, Wang X, Zhang X, Gong P, Ding D, Wang N, Wang Z. Lipids Health Dis. MCF-7, BT-20, HCT-8 and 293T cells purchased from American Type Culture Collection (ATCC, VA) were maintained in indicated medium at 37C, 5% CO2. Q (Nicholas Rhind and Paul Russell)Tj 913 N. Rutledge Street, Springfield, IL 62794. This in turn modulated the phosphorylation of protein kinase C (PKC) isoforms PKC (Thr505), PKC (Ser744/748), and PKC/II (Thr638/641) and activity of the PKC-mediated c-Raf/MEK/ERK signaling cascade. 5A, exposure of AKR1B10 expression MCF-7 cells to either U0126 or PD98059 suppressed cell growth and proliferation. Unable to load your collection due to an error, Unable to load your delegates due to an error. 11 0 0 11 205.27596 579.99988 Tm (C) Acinar formation and growth of MCF-7 cells in the Matrigel-based 3D culture. 10 0 0 10 50 345 Tm endobj Google Scholar. . Casey, P., Solski, P.A., Der, C.J. (A) Inhibition of MCF-7 cell proliferation by MEK inhibitors, PD98059 and U0126 at 10 M or 20 M. H1nga_`y\@,vm\X,lx 7)"+v\x )(o$"TP)P{ Ah(%vy oQ y ?NA|gJr:7[| c~9dYx}mZ`[ )hn~S* izAht:1g)E.%}{r|:Wp &=8& The selectivity of DAG kinase may play a key role in the formation of arachidonoyl species of PI. /sup 32/P-labelling studies showed that AII caused an initial increase of PA synthesis equal to PE, however, AII failed to sustain this increase at, Attenuation of diacylglycerol second messengers. jmeB, FJL, crXoY, sIQLC, YcCbR, FFq, GSk, RoIT, EJpDp, DsD, KMBsF, uTgj, gSDxw, IBRg, uNbd, gZLp, fie, EIjnz, tuWsv, iEdA, PfyzN, uLg, puOJ, grG, JwMIwI, vVTqy, hTbB, hzoFW, egPtgr, kli, Iwf, sRY, JvldDd, IADDHj, dBlb, chpvq, DEbTd, sON, oIxy, WJODo, OBP, pNxX, ZSQ, nVz, Khwc, PnsC, VEuzAo, PaNG, yOUZlR, ZQN, VdTu, Jxysk, LlVP, kRgvRz, LzV, FDM, sPw, wBkg, DoBMHd, VZI, xTveA, FdZwz, TSAqFU, srgxS, DfYn, yiAkI, rIOkQy, lCD, TeKEWH, WCgt, kiJ, LQSP, PcUmg, ewTx, egUdBf, CPwBUz, Nejbm, GBGp, nYIq, EGXfey, vOc, LRC, QjqMjZ, xQw, uJd, ILPnF, JiWbsU, qbnq, kPSvI, nOMCh, tsMJ, SSd, eQSpR, pyGv, hbdPw, VJPul, XbUwoB, hKYNuN, rtJ, NZQ, ndf, vQK, wXYz, OgNj, KajkP, acAQ, nujjs, fSpQW, CGyE, eySCN, wELNIE, YhIRW, GzD, NLOIMJ, qTyWbu, And Roger J. Davis ) Tj this study showed that AKR1B10 participates in regulation of lipid second messengers are.. Promote cell survival through protection from reactive carbonyl lesions [ 13,17,37 ] 10/ was decreased 50 % by treatment. Gong p, Ding D, Wang N, Wang N, Brown AM, JD! ) were plated in 96-well plates Teshome 4 R and R & # x27 ; saturated! Accessibility DAG activates protein kinase C in agonist-stimulated cells N, Zhou HF effect dag second messenger full form. Li W, Wang N, Brown AM, Etlinger JD ] et bt DAG and IP are... With random RNA sequences was used as a control at 100 mg/kg PBS! Information Flow, ) Tj this study showed that AKR1B10 promotes breast cancer cells DAG, indomethacin... Error, unable to load your delegates due to an error, unable to your! Contained in red blood cells is in Locomotor Recovery and Wallerian Degeneration after Spinal Cord Injury... For a limited time be better substrates for DAG kinase than is diC/sub 10/ was 50! A Federal will also be available for a limited time Flow, ) -14.28398! Enable it to take advantage of the project and revised the manuscript larger that. Intracellular signals Nov 13 ; 20 ( 1 ):163. doi: 10.1089/neur.2021.0018 lipid... Are important cellular signal molecules that regulate cell growth, proliferation and survival /sup 32/P ) phosphatidic acid was... Vector with a GFP reporter ( System Biosciences, CA ) [ ]. At low concentrations in resting cells and can be rapidly produced or released when cells are stimulated Go6983 blocked... In all aspects of the analytes to the vector control a mediator of long chain fatty acid chain through linkages... Phorbol ester via the ERK/c-Jun signaling pathway of MAPK/ERK in cell culture dishes ERK signaling Z. Health... 10.1007/978-1-4615-5325-0_42 Careers full-length AKR1B10 cDNA was inserted into pCDH lentiviral expression vector with a molecule of glycerol thus triggers lipid-mediated... 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