Tiam1/Rac1 signaling pathway mediates palmitate-induced, ceramide-sensitive generation of superoxides and lipid peroxides and the loss of mitochondrial membrane potential in pancreatic β-cells

Biochemical Pharmacology

Volumn 80, Issue 6, 2010, Pages 874-883

  Syed, Ismail ^a,b   Jayaram, Bhavaani ^a,b   Subasinghe, Wasanthi ^a,b   Kowluru, Anjaneyulu ^a,b  

^a WAYNE STATE UNIVERSITY   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Ceramide; NADPH oxidase; Oxidative stress; Palmitate; Pancreatic cells; Rac1; Tiam1

Indexed keywords

4 AMINO 6 [2 [[4 (DIETHYLAMINO) 1 METHYLBUTYL]AMINO] 6 METHYL 4 PYRIMIDINYL] 2 METHYLQUINOLINE; CERAMIDE; DIPHENYLIODONIUM SALT; FUMONISIN B1; LIPID PEROXIDE; PALMITIC ACID; PROTEIN CDC42; RAC1 PROTEIN; REACTIVE OXYGEN METABOLITE; RHO KINASE; SUPEROXIDE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CELL ISOLATION; CELL MEMBRANE PERMEABILITY; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; INCUBATION TEMPERATURE; METABOLIC ACTIVATION; MITOCHONDRIAL MEMBRANE POTENTIAL; NONHUMAN; OXIDATIVE STRESS; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; RAT; SIGNAL TRANSDUCTION; SYNTHESIS;

ANIMALS; CELL LINE; CERAMIDES; GUANINE NUCLEOTIDE EXCHANGE FACTORS; INSULIN-SECRETING CELLS; LIPID PEROXIDES; MEMBRANE POTENTIAL, MITOCHONDRIAL; NEOPLASM PROTEINS; PALMITIC ACID; RAC1 GTP-BINDING PROTEIN; RATS; RATS, SPRAGUE-DAWLEY; SIGNAL TRANSDUCTION; SUPEROXIDES;

EID: 77954760363     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2010.05.006     Document Type: Article

References (40)

1. Newsholme P., Haber E.P., Hirabara S.M., Rebelato E.L., Procopio J., Morgan D., et al. Diabetes associated cell stress and dysfunction: role of mitochondrial and non mitochondrial ROS production and activity. J Physiol 2007, 583:9-24.
2. Poitout V., Robertson R.P. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 2008, 29:351-366.
3. Evans J.L., Goldfine I.D., Maddux B.A., Grodsky G.M. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction?. Diabetes 2003, 52:1-8.
4. Morgan D., Oliver-Emilio H.R., Keane D., Hirata A.E., Santos da Rocha M., Bordin S., et al. Glucose, palmitic and pro-inflammatory cytokines modulate production and activity of a phagocyte-like NADPH oxidase in rat pancreatic islets and a clonal cell line. Diabetologia 2007, 50:359-369.
5. Inoguchi T., Li P., Umeda F., Yu H.Y., Kakimoto M., Imamura M., et al. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 2000, 49:1939-1945.
6. Piro S., Anello M., Di Pietro C., Lizzio M.N., Patane G., Rabuazzo A.M., et al. Chronic exposure to free fatty acids or high glucose induces apoptosis in rat pancreatic islets: possible role of oxidative stress. Metabolism 2002, 51:1340-1347.
7. Moore P.C., Ugas M.C., Hagman D.K., Parazzoli S.D., Poitout V. Evidence against the involvement of oxidative stress in fatty acid inhibition of insulin secretion. Diabetes 2004, 53(10):2610-2616.
8. Babior B.M. NADPH oxidase: an update. Blood 1999, 93:1464-1476.
9. Newsholme P., Morgan D., Rebelato E., Oliveira-Emilio H.C., Procopio J., Curi R., et al. Insights into the critical role of NADPH oxidase(s) in the normal and dysregulated pancreatic beta cell. Diabetologia 2009, 52:2489-2498.
10. Geiszt M. NADPH oxidases: new kids on the block. Cardiovasc Res 2006, 71:289-299.
11. Borregaard N., Tauber A.I. Subcellular localization of the human neutrophil NADPH oxidase b-cytochrome and associated flavoprotein. J Biol Chem 1984, 259:47-52.
12. Kowluru A. Small G proteins in islet β-cell function. Endocr Rev 2010, 31:52-78.
13. phox and participates in formyl peptide-mediated neutrophil respiratory burst. J Immunol 2001, 166:1206-1213.
14. Abo A., Pick E., Hall N., Totty N., Teahan C.G., Segal A.W. Activation of the NADPH oxidase involves the small-GTP binding protein p21rac1. Nature 1991, 353:668-670.
15. Knaus U.G., Heyworth P.G., Evans T., Curnutte J.T., Bokoch G.M. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science 1991, 254:1512-1515.
16. Hordijk P.L. Regulation of NADPH oxidases: the role of Rac proteins. Circ Res 2006, 98:453-462.
17. Newsholme P., Keane D., Welters H.J., Morgan N.G. Life and death decisions of the pancreatic β-cell: the role of fatty acids. Clin Sci (Lond) 2007, 112:27-42.
18. Oliver H.R., Verlengia R., Carvalho C.R., Britto L.R., Curi R., Carpinelli A.R. Pancreatic beta-cells express phagocyte-like NAD(P)H oxidase. Diabetes 2003, 52:1457-1463.
19. Uchizono Y., Takeva R., Iwase M., Sasaki N., Oku M., Imoto H., et al. Expression of isoforms of NADPH oxidase components in rat pancreatic islets. Life Sci 2006, 80:133-139.
20. Morgan D., Rebelato E., Abdulkader F., Graciano M.F., Oliveira-Emilio H.R., Hirata A.E., et al. Association of NAD(P)H oxidase with glucose-induced insulin secretion by pancreatic beta-cells. Endocrinology 2009, 150:2197-2201.
21. Inoguchi T., Nawata H. NAD(P)H oxidase activation: a potential target mechanism for diabetes vascular complications, progressive beta-cell dysfunction and metabolic syndrome. Curr Drug Targets 2005, 6:495-501.
22. Sawada F., Inoguchi T., Tsubouchi H., Sasaki S., Fujii M., Maeda Y., et al. Differential effect of sulfonylureas on production of reactive oxygen species and apoptosis in cultured pancreatic beta-cell line, MIN6. Metabolism 2008, 57:1038-1045.
23. Guichard C., Moreau R., Pessayre D., Epperson T.K., Krause K.H. NOX family NADPH oxidase in liver and in pancreatic islets: a role in the metabolic syndrome and diabetes?. Biochem Soc Trans 2008, 36:920-929.
24. Veluthakal R., Suresh M.V., Kowluru A. Down-regulation of expression and function of nucleoside diphosphate kinase in insulin-secreting beta-cells under in vitro conditions of glucolipotoxicity. Mol Cell Biochem 2009, 329:121-129.
25. Veluthakal R., Madathilparambil S.V., McDonald P., Olson L.K., Kowluru A. Regulatory roles for Tiam1, a guanine nucleotide exchange factor for Rac1, in glucose-stimulated insulin secretion in pancreatic beta-cells. Biochem Pharmacol 2009, 77:101-113.
26. Cruz-Monserrate Z., O'Connor K.L. Integrin alpha 6 beta 4 promotes migration, invasion through Tiam1 upregulation, and subsequent Rac activation. Neoplasia 2008, 10:408-417.
27. Kowluru A., Metz S.A. Ceramide-activated protein phosphatase-2A activity in insulin-secreting cells. FEBS Lett 1997, 418:179-182.
28. Veluthakal R., Palanivel R., Zhao Y., McDonald P., Gruber S., Kowluru A. Ceramide induces mitochondrial abnormalities in insulin-secreting INS-1 cells: potential mechanisms underlying ceramide-mediated metabolic dysfunction of the beta cell. Apoptosis 2005, 10:841-850.
29. Gao Y., Dickerson J.B., Guo F., Zheng J., Zheng Y. Rational design and characterization of a Rac GTPase-specific small molecule inhibitor. Proc Natl Acad Sci USA 2004, 101:7618-7623.
30. Shen E., Li Y., Li Y., Shan L., Zhu H., Feng Q., et al. Rac1 is required for cardiomyocyte apoptosis during hyperglycemia. Diabetes 2009, 58:2386-2395.
31. Yi F., Chen Q.Z., Jin S., Li P.L. Mechanism of homocysteine-induced Rac1/NADPH oxidase activation in mesangial cells: role of guanine nucleotide exchange factor Vav2. Cell Physiol Biochem 2007, 20:909-918.
32. Cacicedo J.M., Benjachareowong S., Chou E., Ruderman N.B., Ido Y. Palmitate-induced apoptosis in cultured bovine retinal pericytes: roles of NAD(P)H oxidase, oxidant stress, and ceramide. Diabetes 2005, 54:1838-1845.
33. Kim B.C., Kim J.H. Exogenous C2-ceramide activates c-fos serum response element via Rac-dependent signalling pathway. Biochem J 1998, 330:1009-1014.
34. Embade N., Valerón P.F., Aznar S., López-Collazo E., Lacal J.C. Apoptosis induced by Rac GTPase correlates with induction of FasL and ceramides production. Mol Biol Cell 2000, 11:4347-4358.
35. Deshpande S.S., Qi B., Park Y.C., Irani K. Constitutive activation of rac1 results in mitochondrial oxidative stress and induces premature endothelial cell senescence. Arterioscler Thromb Vasc Biol 2003, 23:e1-e6.
36. Pi J., Bai Y., Zhang Q., Wong V., Floering F.L., Daniel K., et al. Reactive oxygen species as a signal in glucose-stimulated insulin secretion. Diabetes 2007, 56:1783-1791.
37. Koshkin V., Dai F.F., Robson-Doucette A.C., Chan C.B., Wheeler M.B. Limited mitochondrial permeabilization is an early manifestation of palmitate-induced lipotoxicity in pancreatic β-cells. J Biol Chem 2008, 283(12):7936-7948.
38. Jangati G.R., Veluthakal R., Kowluru A. siRNA-mediated depletion of endogenous protein phosphatase 2Acalpha markedly attenuates ceramide-activated protein phosphatase activity in insulin-secreting INS-832/13 cells. Biochem Biophys Res Commun 2006, 348(2):649-652.
39. Guo J., Qian Y.Y., Xi X.X., Hu X.H., Zhu J.X., Han X. Blockage of ceramide metabolism exacerbates palmitate inhibition of pro-insulin gene expression in pancreatic β-cells. Mol Cell Biochem 2010, 338:283-290.
40. D'Aleo V., Del Guerra S., Martano M., Bonamassa B., Canistro D., Soleti A., et al. The non-peptidyl low molecular weight radical scavenger IAC protects human pancreatic islets from lipotoxicity. Mol Cell Endocrinol 2009, 309(1-2):63-66.