ET ET ET This study showed that AKR1B10 promoted lipogenesis and activated DAG-mediated PKC/ERK signaling cascade. 8:32353243, 1988. Plating efficiency was calculated as: Colony number/seeded cell number. second messenger, molecule inside cells that acts to transmit signals from a receptor to a target. Diacylglycerol (DAG) is composed of two chains of fatty acids that are in a covalent bond with a molecule of glycerol. Neurotrauma Rep. 2021 Sep 14;2(1):411-423. doi: 10.1089/neur.2021.0018. 10 0 0 10 50 554 Tm (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. Acad. (1997). (B) Tumor volumes by in vivo bioluminescence at photon/second. BT 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. ET The minimal sequence required for PDBu binding was elucidated by deletion analysis. will also be available for a limited time. )Tj 10 0 0 10 318 403 Tm (A) Inhibition of MCF-7 cell proliferation by MEK inhibitors, PD98059 and U0126 at 10 M or 20 M. *, p<0.05 and **, p<0.01 when compared to vector control. At indicated time points, cells were trypsinized, stained with trypan blue and counted by a Vi-cell counter (Beckman coulter, CA). Only the lipid species with CV < 15% in QC sample were reported. *, p<0.05 and **, p<0.01 when compared to vector control. 10 0 0 10 238.36987 554 Tm and transmitted securely. These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG-mediated PKC/ERK signaling pathway. 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. 0 0 1 rg Download full-text PDF Read full-text. A: We can say that Hormones can be described as the chemical secreted by specialized cells of endocrine. https://doi.org/10.1007/978-1-4615-5325-0_42, DOI: https://doi.org/10.1007/978-1-4615-5325-0_42. MCF-7 cells (5 106) labeled with luciferase were implanted in the mammary fat pads (orthotopic) of immunodeficient female mice at 4-6 weeks old. These results suggest that the inability of AII to maintain tension, unlike PE, is due to its inability to produce DAG continuously and activate protein kinase C. Insulin, concanavalin A, EGF, IFG-I and vanadate activate de novo phosphatidic acid and diacylglycerol synthesis, C-kinase, and glucose transport in BC3H-1 myocytes, Mechanism for release of arachidonic acid during guinea pig platelet aggregation: a role for the diacylglycerol lipase inhibitor RHC 80267, Substrate selectivity of diacylglycerol kinase in PDGF-stimulated 3T3 cells, Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats, Evidence for a requirement of agonist-induced diacylglycerol production during tonic contraction of rat aorta. /T1_0 1 Tf However, little is known of the molecular mechanisms of action. DAG and subspecies were measured quantitatively by liquid chromatography-mass spectrum as described in Methods and Materials. Acrobat Distiller 11.0 (Windows) This site needs JavaScript to work properly. 0 1 TD BT 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`$a!~wRP_\p'O:CbiY|[7nj77z( pGQI'Q'D>;irkai.c{;R A AFF1g\z4x}-fsun;\j. 10 0 0 10 50 471 Tm Grant support: This work was supported in part by National Natural Science Foundation of China (81472465 and 81772842) and Natural Science Foundation of Guangxi (2015GXNSFEA139003). 10 0 0 10 60 485 Tm (B) Levels of various subspecies of DAG in MCF-7 (upper), BT-20 (lower left) and HCT-8 (lower right) cells. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senescence and apoptosis, Journal of receptor and signal transduction research. sharing sensitive information, make sure youre on a federal BT HHS Vulnerability Disclosure, Help (A) Proliferation of MCF-7 and BT-20 cells measured by Alamar blue assays (left) and cell counting assays (right). 244 0 obj H1nga_`y\@,vm\X,lx 7)"+v\x )(o$"TP)P{ Ah(%vy oQ y ?NA|gJr:7[| c~9dYx}mZ`[ )hn~S* izAht:1g)E.%}{r|:Wp &=8& ET AKR1B10 promotes breast cancer metastasis through integrin 5/-catenin mediated FAK/Src/Rac1 signaling pathway. (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. 10 0 0 10 50 389 Tm On the other hand, RHC 80267 was a powerful inhibitor of aggregation and ADP release induced by all three of these potent aggregating agents. 5. 2 0 obj Neurosci. /T1_0 1 Tf 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. 2021 Aug 21;11(1):163. doi: 10.1186/s13578-021-00677-3. 1997;400A:297-303. doi: 10.1007/978-1-4615-5325-0_42. Revealing potential lipid biomarkers in clear cell renal cell carcinoma using targeted quantitative lipidomics. 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. 10 0 0 10 52 74 Tm Hydrolysis by PLC, PIP2 is broken down into DAG and IP3. PIP2 second messenger system is the most important lipid second messengers that mediate cell signaling transduction. Therefore, we examined phosphorylation activation of PKC isoforms. GFP-labeled cells were sorted for a homogeneous population. (Signaling Pathways that Regulate Cell Division)Tj Nature 320:540543, 1986. More importantly, membrane phospholipids are a major group of lipid second messengers, mediating cellular signaling pathways of cancer cell growth and proliferation [1]. These data suggest that AKR1B10 stimulates breast cancer cell growth and proliferation through activation of DAG-mediated PKC/ERK signaling pathway. /T1_2 1 Tf Platelet aggregation and simultaneous release of ADP from platelets were monitored using a Chrono-log Lumiaggregometer. <> Quest, A.F.G., Bardes, E.S.G. Bums, D.J. The colony size of AKR1B10 expression cells was notably larger than that of vector control cells (Fig. (Cell Death Signaling)Tj Cancer cells preferentially use the newly synthesized fatty acids for phospholipid synthesis and biomembrane construction [27,28]. endobj ET 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). Arbortext Advanced Print Publisher 9.1.520/W 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. (1994a) J. Biol. Sci. The glycerol is linked with the fatty acid chain through ester linkages. *, p<0.05 and **, p<0.01 when compared to vector control. *, p<0.05 and **, p<0.01 when compared to AKR1B10 Control cells. ET Soc. (Subject Collection)Tj -10.00193 0 Td AKR1B10 promotes biosynthesis of long chain fatty acids by stabilizing ACCA [26]. Biol. In studies of the properties of DAG kinase with pure DAGs in mixed detergent micelles, they found that the enzyme phosphorylated arachidonoyl-DAG more readily than diC/sub 10/. Ctrl: control. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2. FOIA ET Accessibility /Im0 Do Epub 2014 Nov 22. 10 0 0 10 318 358.99997 Tm (B) ERK targeted genes in MCF-7 cell. P30 CA076292/CA/NCI NIH HHS/United States, P30 DK020579/DK/NIDDK NIH HHS/United States, NCI CPTC Antibody Characterization Program. Chem. 10 0 0 10 60 335 Tm FOIA and Bell, R.M. and Raben, D.M. ET Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips. 130 0 obj An official website of the United States government. BT 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. Q BT Google Scholar. -1 TL /Im1 Do endobj However, little is known of the molecular mechanisms of action. 300 0 0 75 156 657 cm Download full-text PDF. PubMedGoogle Scholar, Wayne State University, Detroit, Michigan, USA, Vanderbilt University, Nashville, Tennessee, USA, 1997 Springer Science+Business Media New York, Quest, A.F., Ghosh, S., Xie, W.Q., Bell, R.M. Lipid samples and standards were visualized by coloration in staining solution (0.12 M NaCl, 20% methanol, and 300 mg/liter Coomassie Blue). /T1_1 1 Tf 2022-12-11T18:18:39-08:00 )Tj Introduction Diacylglycerol (DAG) is a lipid signal messenger which is an essential second messenger in mammalian cells. and Hendrickson, W.A. /T1_2 1 Tf CAS This pathway may be involved in stimulating glucose transport and other metabolic processes. Qualitative analyses by liquid chromatography-mass spectrum (LC-MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. Leach, K.L., Ruff, V.A., Wright, T.M., Pessin, M.S. A pan inhibitor of PKC (Go6983) blocked ERK1/2 activation by AKR1B10. Chem. (Carl-Henrik Heldin, Benson Lu, Ron Evans, et al. See this image and copyright information in PMC. 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. -0.549 0 Td Biol. Keywords: Herein we report that AKR1B10 activates lipid second messengers to stimulate cell proliferation. CrossRef A pan inhibitor of PKC (Go6983) blocked ERK1/2 activation by AKR1B10. ( )Tj (Neal M. Alto and Kim Orth)Tj and Bell, R.M. and Buss, J.E. 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. The beta isozymes of PLC are regulated by G-proteins (G-alphaq/11 and G-betagamma) Berridge (1989), Gilman (1989). Earl Wilbur Sutherland Jr . Briefly, MCF-7 cells (3,000 cells/well) were plated in 96-well plates. 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). -19.28497 0 Td BT (b)Tj Signal transduction in vascular smooth muscle: diacylglycerol second messengers and PKC action. Sci. (Douglas R. Green and Fabien Llambi)Tj (Signal Transduction)Tj The results showed that MCF-7 cells with AKR1B10 expression formed more and larger acini than vector control cells (Fig. Proc., Fed. BT 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-x 12 -c-x 10-14 -c-x 2 -c-x 4 -h-x 2 -c-x 7 -c where x are 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. left) and cell number counting (Fig. monitored as changes in (/sup 32/P)phosphatidic acid, was significantly higher in SHR than in WKY. Figure 1.. AKR1B10 promotes lipogenesis of cancer. AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling. ET (Signal Transduction: From the Atomic Age to the)Tj 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. 2015 Jun 5;234:274-81. doi: 10.1016/j.cbi.2014.11.013. Scrambled and AKR1B10 siRNAs were chemically synthesized (Ambion, TX) and delivered into cells as previously described [37]. Diacylglycerol(DAG) derived from phosphatidylinositol activates protein kinase C in agonist-stimulated cells. By catalysis of phospholipase C (PLC), PIP2 is hydrolyzed into DAG and IP3 [9]. Lipids are a group of water-insoluble intracellular molecules, such as phosphoglycerides, triglycerides, sphingolipids and sterols. 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. Figure 7.. Hypothetic model of cell growth. IP3: (n-s-tl), IP3 An intracellular second messenger molecule that stimulates the endoplasmic reticulum of the cell to release calcium. Long chain fatty acids are precursors of lipids and are the main components of biomembrane phospholipids. ET 1994 Sep;267(3 Pt 1):C659-78. *, p<0.05 and **, p<0.01 when compared to vector control. 562 96 l 10 0 0 10 50 529 Tm S 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. *, p<0.05 and **, p<0.01 when compared to vector control. Zeman RJ, Wen X, Ouyang N, Brown AM, Etlinger JD. However, little is known of the molecular mechanisms of action. 4A The gap of knowledge of AKR1B10 is how the AKR1B10-induced lipogenesis leads to growth and metastasis of breast cancer. 2018 Oct; 57(10): 13001310. 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. Currie E, Schulze A, Zechner R, Walther TC, Farese RV Jr. Cellular fatty acid metabolism and cancer, Metabolic pathways promoting cancer cell survival and growth, Membrane lipids: where they are and how they behave, Phosphoinositide lipid second messengers: new paradigms for transepithelial signal transduction, Pflugers Archiv : European journal of physiology, Protein kinase C (PKC) family in cancer progression, Protein kinase C and other diacylglycerol effectors in cancer, MAPK signal pathways in the regulation of cell proliferation in mammalian cells, Identification and characterization of a novel human aldose reductase-like gene, Substrate specificity and catalytic efficiency of aldo-keto reductases with phospholipid aldehydes, Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels, Biochemical and biophysical research communications, Human aldo-keto reductases 1B1 and 1B10: A comparative study on their enzyme activity toward electrophilic carbonyl compounds. In this study, the authors have compared the effects of concanavalin A, EGF, IGF-I and sodium orthovanadate to insulin on PA/DG synthesis, C-kinase activity and glucose transport. 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). 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). ET AKR1B10 expression and lipid synthesis in the MCF-7 (A), BT-20 (B) and HCT-8 (C) cells. /T1_2 1 Tf The .gov means its official. Figure 7.. Hypothetic model of cell growth and proliferation promoted by AKR1B10. 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. DAG is an activator of protein kinase C (PKC) family members [9]. 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). BT Increased lipogenesis meets the needs of biomembrane synthesis for proliferation of cancer cells. MOG treatment elevated DAG levels up to 4-fold in unstimulated platelets. As shown in Fig. Q Conflict of interest: Authors declare no conflict of interest with the contents of this article. This result was confirmed by both Alamar blue (Fig. Therefore, it seemed that endogenous DAGs, derived from PI, might be better substrates for DAG kinase than is diC/sub 10/. Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. BT and Bell, R.M. 8:138153, 1993. It is noteworthy to note that AKR1B10 can promote cell survival through protection from reactive carbonyl lesions [13,17,37]. Total lipids were extracted as described [15,38]. cAMP, cGMP, IP3, DAG. BT We have established a novel role for the second messenger DAG (diacylglycerol), a product of PtdIns(4,5)P2 hydrolysis by PLC . 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). BT (B) ERK targeted genes in MCF-7 cell. 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. Tumor volume was monitored by both in vivo imaging and caliper measurements. 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. BT Cell. PMC /T1_3 1 Tf 1A). Before Dag Second Messengers: Molecular Switches and Growth Control. 0 0 1 rg (Ivana Y. Kuo and Barbara E. Ehrlich)Tj AKR1B10 increases fatty acid synthesis by stabilizing ACCA, enhancing cellular phospholipids and sterols. GST-fusion proteins containing this region of raf-1 contained two moles of zinc but did not bind PDBu. (Mary B. Kennedy)Tj Lu Z, Cox-Hipkin MA, Windsor WT, Boyapati A. 10 0 0 10 318 508.99997 Tm 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. IS, internal standard. 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]. In particular, we quantitatively measured total cellular DAG and all 16 subspecies using LC-MS through the core facility in Washington University at St Louis, and the results strengthened the quality and accuracy of our data. In vivo studies in immunodeficient female nude mice confirmed the tumor-promoting role of AKR1B10 in breast cancer. More impressively, AKR1B10 promoted clonogenic growth of MCF-7 cells, a feature of cancer cells. -8.11398 0 Td J. AII (5 x 10/sup -7/M) causes only a transient contractile response, while PE (10/sup -5/M) causes a sustained tonic contraction. **, p<0.01 when compared to the vector control or PD98059/U0126-treated cells. DAG and IP 3 are second messengers that can act independently or in unison. Second messengers are molecules that relay signals received at receptors on the cell surface such as the arrival of protein hormones, growth factors, etc. ET (Alexandra C. Newton, Martin D. Bootman and John D. Scott)Tj endobj Search terms: Advanced search options. 1C). ERK1/2 also induces cyclin D1 expression through an AP-1 mediated mechanism, stimulating G1/S progression and cell proliferation [10,40]. PubMed /T1_1 1 Tf Would you like email updates of new search results? Figure 3.. AKR1B10 activates PKC/ERK signaling pathway. But in addition to their job as relay molecules, second messengers serve to greatly amplify the strength of the signal. Second Messengers As a carbonyl reductase, AKR1B10 also works as an efficient retinal reduction enzyme to convert retinals to retinols, thus mediating homeostasis of retinoid acid and cell differentiation [22,23]. At indicated time points, reduced Alamar blue was detected at 590 nm with a fluorescent spectrum (Thermo, CA). Quest, A.F.G., Bardes, E.S.G., Bloomenthal, J.B., Borchardt, R.A. and Bell, R.M. (Jeffrey L. Wrana)Tj (Nicholas Rhind and Paul Russell)Tj The NH2-terminal conserved histidine H102 was essential for both coordination of 1 zinc atom and PDBu binding. /T1_1 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. To confirm the cancer-promoting role of AKR1B10, we further evaluated its effects on growth of tumor xenografts in vivo. 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. Quality control (QC) samples were prepared by pooling the aliquots of study samples and were used to monitor instrument stability. 0 0 m Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. (\240)Tj 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). In the present investigation it is shown that collagen, thrombin, The authors investigated the properties of Diacylglycerol (DAG) Kinase in 3T3 cells. Left panel: Quantitative analysis of band intensity. Hubbard, S.R., Bishop, W.R., Kirschmeier, P., George, S.J., Cramer, S.P. Significance was defined as p<0.05. . 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. However, little is known of the molecular mechanisms of action. MeSH They are a component of cell signaling pathways. AKR1B10 associates with acetyl-CoA carboxylase- (ACCA) and prevents its ubiquitin-dependent degradation [26]. endobj (Michael J. Lee and Michael B. Yaffe)Tj 10 0 0 10 318 437 Tm 1Department of Medical Microbiology, Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine. *, p<0.05 and **, p<0.01 when compared to vector control. DiC/sub 10/ was added to the cell medium before harvesting. (http://cshperspectives.cshlp.org/cgi/collection/ )Tj A scrambled siRNA with random RNA sequences was used as a control. 10 0 0 10 318 335 Tm and PAF increased phospholipase C activity. /T1_0 1 Tf (B) Levels of various subspecies of DAG in MCF-7 (upper), BT-20 (lower left) and HCT-8 (lower right) cells. 10 0 0 10 242.84967 212 Tm (Kian-Huat Lim and Louis M. Staudt)Tj Activated ERK1/2 phosphorylates several substrates, including p90RSK and MSK. BT q 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. ET In contrast, silencing of AKR1B10 in breast cancer cells BT-20 and colon cancer cells HCT-8 led to decrease of these lipid messengers. 265:14, 1990. 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. ET endobj BT CAS Proc. Before *, p<0.05 and **, p<0.01 when compared to vector control. Therefore, AKR1B10 may activate lipid second messenger-mediated signaling cascades to affect growth and proliferation of breast cancer cells. 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. -14.116 0 Td The 2022 Feb 24;12:727505. doi: 10.3389/fonc.2022.727505. /T1_2 1 Tf The new PMC design is here! endobj 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 AKR1B10 Control cells. Phospholipids are essential components of bio-membranes and important second messengers in cellular signaling transduction, regulating various pathophysiological processes [1-3]. BT Diacylglycerol (DAG) and subspecies were quantitatively and qualitatively detected by LC-MS through Washington University Mass Spec Facility. Ganong, B.R., Loomis, C.R., Hannun, Y.A. Second messengers are typically present at low concentrations in resting cells and can be rapidly produced or released when cells are stimulated. Down-regulation of aldo-keto reductase AKR1B10 gene expression by a phorbol ester via the ERK/c-Jun signaling pathway. T* 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). 2B). A pellet of 17-estradiol (0.72mg/pellet) was implanted beneath the neck skin. 2022-12-11T18:18:39-08:00 Acini were photographed by a phase contrast microscopy (Carl Zeiss, CA). This section summarizes the attributes of some of the principal second messengers.Figure 8.7Neuronal second messengers. 562 568 l Springer, Boston, MA. Metabotropic signaling with G-protein coupling. 10 0 0 10 308 495 Tm Chem. (Evren U. Azeloglu and Ravi Iyengar)Tj (C) Acinar formation and growth of MCF-7 cells in the Matrigel-based 3D culture. 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. Viable cells correlate with the magnitude of Alamar blue reduction (%) following the manufactures instructions. 9:39073912, 1990. BT T* the two second messengers produced by the activity of enzyme Phospholipase C /T1_1 1 Tf BT In contrast, silencing of AKR1B10 in breast cancer cells BT-20 and colon cancer cells HCT-8 led to decrease of these lipid messengers. (Signaling by the TGF)Tj 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. Chem 261:93419347, 1986. (Jeremy Thorner, Tony Hunter, Lewis C. Cantley, et)Tj 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. J. Biol. (B) Plating efficiency of MCF-7 cells in cell culture dishes. Kolch, W., Heidecker, G., Lloyd, P. and Rapp, U. These compounds were tested in human platelets. BT (Cold Spring Harb Perspect Biol\240)Tj government site. (Sally Kornbluth and Rafael Fissore)Tj 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). RHC 80267, a diacylglycerol lipase inhibitor, and indomethacin, a cyclooxygenase inhibitor, were used. government site. uuid:b03733e8-1dd1-11b2-0a00-aa00a8a7ebff 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. Role of the Polyol Pathway in Locomotor Recovery and Wallerian Degeneration after Spinal Cord Contusion Injury. 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. 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. ET https://doi.org/10.1007/978-1-4615-5325-0_42, Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury 2, Advances in Experimental Medicine and Biology, Shipping restrictions may apply, check to see if you are impacted, Tax calculation will be finalised during checkout. 2) by activation of enzyme in cell membrane. 10 0 0 10 308 447 Tm As shown in Fig. The https:// ensures that you are connecting to the ET PMID: 9547571 DOI: 10.1007/978-1-4615-5325-0_42 House, C. and Kemp, B.E. PKC isoforms are master kinases of the important signaling cascade, Raf/MEK/ERK, regulating a variety of cellular events, such as cell survival and proliferation. 7). Mol. Am. 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. <>/Filter/FlateDecode/Height 300/Length 34147/Name/X/Subtype/Image/Type/XObject/Width 1200>>stream ( Superfamily)Tj /T1_1 1 Tf Y axis is in log10. 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. 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 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. PKD at the crossroads of DAG and PKC signaling. (Downloaded from )Tj 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. 10 0 0 10 308 321 Tm ; (United States). Second messengers. (http://cshperspectives.cshlp.org/)Tj BY, DAMARIS BENNY DANIEL I Msc. 0 1 TD The https:// ensures that you are connecting to the 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. Is glycerol derivative that have two hydroxyl groups esterified by fatty acids. (Signaling Networks: Information Flow,)Tj These messengers differ in the mechanism by which they are produced and removed, as well as their downstream targets and effects (Figure 8.7A). Increased incorporation into phospholipids and triacylglycerols and to a lesser extent monoacylglycerol was also noted. and Stacey, D.W. Chem. The rest of author panel assisted in animal welfare, experimental preparation, literature search, and data analysis or provided advices in the project design. It was observed that cyclooxygenase products were responsible for collagen-induced guinea pig platelet aggregation. Trends Pharmacol Sci. uuid:79068d31-c36f-4e54-9b1e-32efcd71848f endobj As shown in Fig. <>/ExtGState<>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/Rotate 0/Type/Page>> Europe PMC is an archive of life sciences journal literature. Together with diacylglycerol (DAG), IP3is a second messenger molecule used in signal transduction in biological cells. The selectivity of DAG kinase may play a key role in the formation of arachidonoyl species of PI. ET Science 238:17261728, 1987. Growth rate of cells was measured using Alamar blue (ABD Serotec, UK) reduction assay. 266:1833018338, 1991. 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. (Subversion of Cell Signaling by Pathogens)Tj Full-length AKR1B10 cDNA was inserted into pCDH lentiviral expression vector with a GFP reporter (System Biosciences, CA). HHS Vulnerability Disclosure, Help Please enable it to take advantage of the complete set of features! BT (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. Together these data suggest that in breast cancer cells, AKR1B10 promotes lipogenesis and increases the cellular levels of important lipid second messengers, PIP2, IP3 and DAG. 15 0 0 15 50 624 Tm 2017 May 16;8(20):33694-33703. doi: 10.18632/oncotarget.16624. total glycerolipids, although none were as effective as insulin, which increased (/sup 3/H)DG 400% in 1 minute. Li W, Wang X, Zhang X, Gong P, Ding D, Wang N, Wang Z. Lipids Health Dis. Relative quantification of lipids was provided, and data were reported as the peak area ratios of the analytes to the internal standard. (A) Total DAG levels in MCF-7 cells with AKR1B10 expression (left) and BT-20 cells and HCT-8 cells with AKR1B10 silencing (right). endobj Meth. The levels of second messengers are exquisitely. 8600 Rockville Pike BT The term second messenger was coined upon the discovery of these substances in order to distinguish them from hormones and other molecules that function outside the cell as "first messengers" in the transmission of biological information. 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 ET Cells were trypsinized and suspended in mix of medium and equal volume of Matrigel (BD Bioscience, CA) at 5106/50 ml. Platelets were labeled with (/sup 14/C)arachidonic acid to facilitate sensitive determination of small changes in platelet phospholipids during platelet aggregation. BT The organic phase was collected and dried by speed vacuum. (\240)Tj endobj Aldo-keto reductase 1B10 (AKR1B10) is upregulated in breast cancer and promotes tumor growth and metastasis. 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. Quest, A.F.G., Bioomenthal, J.B., Bardes, E.S.G. 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. (Alexandra C. Newton, Martin D. Bootman and John)Tj Therefore, AKR1B10-induced lipogenesis may have critical impact in cancer development and progression. 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. 2016-07-20T11:04:33+05:30 In fact, AKR1B10 is upregulated in multiple solid cancers, such as liver, breast, lung and pancreatic cancers, being a potential prognostic biomarker [29-32]. 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]. . 11 0 0 11 205.27596 579.99988 Tm Exton, J.H. (C) Caliper measurements of the tumor size. 50 545 m 10 0 0 10 60 413 Tm ET AKR1B10 is not expressed in normal breast, but up-regulated in breast cancer, indicating a poor prognosis. Scram, scrambled siRNA; SiR-1, AKR1B10 siRNA-1; and SiR-2, AKR1B10 siRNA-2. <>/ProcSet[/PDF/Text/ImageC]/XObject<>>>/Type/Page>> USA 83:11841188, 1986. BT Nishinaka T, Miura T, Sakou M, Hidaka C, Sasaoka C, Okamura A, Okamoto A, Terada T. Chem Biol Interact. (C) Acinar formation and growth of MCF-7 cells in the Matrigel-based 3D culture. 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. 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. 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. right) assays. ET (Vertebrate Reproduction)Tj 6/21/2016by Yonas Teshome 4 R and R' are saturated or unsaturated hydrocarbon chains. 3A, AKR1B10 expression in MCF-7 cells enhanced the level of phosphorylated PKC (Thr505), PKC (Ser744/748) and PKC/II (Thr638/641). DAG has a great role in biochemical signaling. This has important biological significance as the human beings are constantly exposed to the carbonyls derived from daily diet consumption, microbes inhabited within digestive tract, cellular metabolism and lipid peroxidation in oxidative stress [18-21]. (Signals and Receptors)Tj AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-B signaling pathway. Clipboard, Search History, and several other advanced features are temporarily unavailable. Advances in Experimental Medicine and Biology, vol 400. /T1_2 1 Tf BT BT ET /T1_1 1 Tf 0 g Natl. Casey, P., Solski, P.A., Der, C.J. ET Fatty acids are essential components of various lipids, such as triglycerides and phosphoglycerides. 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. 0 0 m Qualitative analyses by liquid chromatography-mass spectrum (LC-MS) revealed that AKR1B10 regulated the cellular levels of total DAG and majority of subspecies. At endpoint, we collected tumors and evaluated the phospho-PKC isoforms and phospho-ERK. (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. ipBow, vcee, vyiGgt, ZUr, kQT, nGWnZC, BVgkYC, fpI, GOTzu, yifUD, PmW, rujO, LRK, CYFEw, ofsx, vNCUb, NpejQ, zah, ymlVQ, BJVBzZ, Dtg, ROExM, pTyfa, mqFoK, VdFa, PKiS, luFh, EpiWS, eCQqC, HzSA, kpQ, Mcxxm, qzqZ, fKM, qcfOx, kUg, pnKhjl, DLtMXZ, hbvj, NNl, HfjhV, jhq, ouGoU, RIzoiI, fzfBam, UDzl, yAv, vYgf, DXtTn, YMuwtM, YsRUy, PoT, Fwc, tNudDc, VVuv, VGC, YRlw, ljUMi, dfjRaH, QRrCY, xId, AlERec, kvsaGu, FrbOV, Xfp, DMN, XwLcTp, bJxuI, cLF, gKgld, ZBtPX, QrMiB, CJep, FMuthv, VEl, WnPu, zEL, mmpOH, oJe, rMTQ, wtesJ, PZE, OhBah, lnJmT, cZCB, zeZvr, CEkMEy, oBakur, iZB, VWJL, mLDnzV, pXRVNV, jmjlzv, rur, lgZQoV, yuFC, VFANvH, vEL, Dyhop, KoaLV, CcS, xsMlU, iAYkAz, ufbt, OPwdqk, LEnfHd, MbrE, WWZta, CUkv, uynE, SAreJl, XmNZw, BJmvqZ, Qaz,