The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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The Role of Janus Kinase in Superoxide-mediated Proliferation of Diabetic Vascular Smooth Muscle Cells

  • Lee, Ji-Young (Department of Pharmacology, College of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University) ;
  • Park, Ji-Young (Department of Pharmacology, College of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University) ;
  • Kim, Chi-Dae (Department of Pharmacology, College of Medicine, and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University)
  • Published : 2007.02.28
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Abstract

To elucidate a potential molecular link between diabetes and atherosclerosis, we investigated the role of Janus tyrosine kinase(JAK) for NAD(P)H oxidase-derived superoxide generation in the enhanced proliferative capacity of vascular smooth muscle cells(VSMC) of Otsuka Long-Evans Tokushima Fatty(OLETF) rat, an animal model of type 2 diabetes. An enhanced proliferative response to 10% fetal bovine serum(FBS) and superoxide generation with an increased NAD(P)H oxidase activity were observed in diabetic(OLETF) VSMC. Both the enhanced proliferation and superoxide generation in diabetic VSMC were significantly attenuated by AG490, JAK2 inhibitor, and PP2, Src kinase inhibitor. Tyrosine phosphorylation of proteins in diabetic VSMC, especially JAK2, was increased compared to control VSMC. Furthermore, the enhanced NAD(P)H oxidase activity in diabetic VSMC was significantly attenuated by AG490 in a dose-dependent manner. Together, these results indicate that the signal pathway which leads to diabetes-associated activation of Src kinase/JAK is critically involved in the diabetic VSMC proliferation through NAD(P)H oxidase activation and superoxide generation.

Keywords

References

  1. Cahilly C, Ballantyne CM, Lim DS, Gotto A, Marian AJ. A variant of p22(phox), involved in generation of reactive oxygen species in the vessel wall, is associated with progression of coronary atherosclerosis. Circ Res 86: 391-395, 2000 https://doi.org/10.1161/01.RES.86.4.391
  2. Campbell GS, YuCL, Jove R, Carter-Su C. Constitutive activation of JAK1 in Src-transformed cells. J Biol Chem 272: 2591-2594, 1997 https://doi.org/10.1074/jbc.272.5.2591
  3. Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFN and other extracellular signaling proteins. Science 264: 1415-1421, 1994 https://doi.org/10.1126/science.8197455
  4. Darnell JE Jr. Studies of IFN-induced transcriptional activation uncover the Jak-Stat pathway. J Interferon Cytokine Res 18: 8549-8554, 1998
  5. DaSilva L, Howard OM, Rui H, Kirken RA, Farrar WL. Growth signaling and JAK2 association mediated by membrane-proximal cytoplasmic regions of prolactin receptors. J Biol Chem 269: 18267-18270, 1994
  6. Faries PL, Rohan DI, Takahara H, Wyers MC, Contreras MA, Quist WC, King GL, Logerfo FW. Human vascular smooth muscle cells of diabetic origin exhibit increased proliferation, adhesion, and migration. J Vasc Surg 33: 601-607, 2001 https://doi.org/10.1067/mva.2001.111806
  7. Garcia MJ, McNamara PM, Gordon T, Kannel WB. Morbidity and mortality in diabetes in the Framingham population. Sixteenyear follow-up study. Diabetes 23: 105-111, 1974 https://doi.org/10.2337/diab.23.2.105
  8. Griendling KK, Alexander RW. Oxidative stress and cardiovascular disease. Circulation 96: 3264-3265, 1997
  9. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circulation Research 74: 1141-1148, 1994 https://doi.org/10.1161/01.RES.74.6.1141
  10. Griendling KK, Sorescu D, Ushio-Fukai M. NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86: 494-501, 2000 https://doi.org/10.1161/01.RES.86.5.494
  11. Habib A, Creminon C, Frobert Y, Grassi J, Pradelles P, Maclouf J. Demonstration of an inducible cyclooxygenase in human endothelial cells using antibodies raised against the carboxyl-terminal region of the cyclooxygenase-2. J Biol Chem 268: 23448- 23454, 1993
  12. Inoue N, Kawashima S, Kanazawa K, Yamada S, Akita H, Yokoyama M. Polymorphism of the NADH/NADPH oxidase p22 phox gene in patients with coronary artery disease. Circulation 97: 135-137, 1998 https://doi.org/10.1161/01.CIR.97.2.135
  13. Kannel WB, McGree DL. Diabetes and cardiovascular disease. The Framingham study. JAMA 241: 2035-2038, 1979 https://doi.org/10.1001/jama.241.19.2035
  14. Kim YK, Lee MS, Son SM, Kim IJ, Lee WS, Kim CD. Vascular NADH oxidase is involved in impaired endothelium-dependent vasodilation in OLETF rats, a model of type 2 diabetes. Diabetes 51: 522-527, 2002 https://doi.org/10.2337/diabetes.51.2.522
  15. Madamanchi NR, Li S, Patterson C, Runge MS. Reactive oxygen species regulate heat-shock protein 70 via the JAK/STAT pathway. Arterioscler Thromb Vasc Biol 21: 321-326, 2001 https://doi.org/10.1161/01.ATV.21.3.321
  16. Marrero MB, Schieffer B, Li B, Sun J, Harp, JB, Ling BN. Role of janus kinase/signal transducer and activator of transcription and mitogen-activated protein kinase cascades in angiotensin IIand platelet-derived growth factor-induced vascular smooth muscle cell proliferation. J Biol Chem 272: 24684-24690, 1997 https://doi.org/10.1074/jbc.272.39.24684
  17. Modesti A, Bertolozzi I, Gamberi T, Marchetta M, Lumachi C, Coppo M, Moroni F, Toscano T, Lucchese G, Gensini GF, Modesti PA. Hyperglycemia activates JAK2 signaling pathway in human failing myocytes via angiotensin II-mediated oxidative stress. Diabetes 54: 394-401, 2005 https://doi.org/10.2337/diabetes.54.2.394
  18. Pelletier S, Duhamel F, Coulombe P, Popoff MR, Meloche S, Rho family GTPases are required for activation of Jak/STAT signaling by G protein-coupled receptors. Mol Cell Biol 23: 1316- 1333, 2003 https://doi.org/10.1128/MCB.23.4.1316-1333.2003
  19. Proietti C, Salatino M, Rosemblit C, Carnevale R, Pecci A, Kornblihtt AR, Molinolo AA, Frahm I, Charreau EH, Schillaci R, Elizalde PV. Progestins induce transcriptional activation of signal transducer and activator of transcription 3 (Stat3) via a Jak- and Src-dependent mechanism in breast cancer cells. Mol Cell Biol 25: 4826-4840, 2005 https://doi.org/10.1128/MCB.25.12.4826-4840.2005
  20. Ren Z, Schaefer TS. ErbB-2 activates Stat3 alpha in a Src- and JAK2-dependent manner. J Biol Chem 277: 38486-38493, 2002 https://doi.org/10.1074/jbc.M112438200
  21. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362: 801-809, 1993 https://doi.org/10.1038/362801a0
  22. Ross R. Cell biology of atherosclerosis. Annu Rev Physiol 57: 791- 804, 1995 https://doi.org/10.1146/annurev.ph.57.030195.004043
  23. Ruderman NB, Haudenschild C. Diabetes as an atherogenic factor. Prog Cardiovasc Dis 26: 373-412, 1984 https://doi.org/10.1016/0033-0620(84)90011-2
  24. Ruef J, Liu SQ, Bode C, Tocchi M, Srivastava S, Runge MS, Bhatnagar A. Involvement of aldose reductase in vascular smooth muscle cell growth and lesion formation after arterial injury. Arterioscler Thromb Vasc Biol 20: 1745-1752, 2000 https://doi.org/10.1161/01.ATV.20.7.1745
  25. Ruef J, Peter K, Nordt TK, Runge MS, Kubler W, Bode C. Oxidative stress and atherosclerosis: its relationship to growth factors, thrombus formation and therapeutic approaches. Thromb Haemost 82: 32-37, 1999 https://doi.org/10.1055/s-0037-1615550
  26. Schieffer B, Luchtefeld M, Braun S, Hilfiker-Kleiner D, Drexler H. Role of NAD(P)H oxidase in angiotensin II-induced JAK/STAT signaling and cytokine induction. Circ Res 87: 1195-1201, 2000 https://doi.org/10.1161/01.RES.87.12.1195
  27. Seki Y, Kai H, Shibata R, Nagata T, Yasukawa H, Yoshimura A, Lmaizumi T. Role of the JAK/STAT pathway in rat carotid artery remodeling after vascular injury. Circ Res 87: 12-18, 2000 https://doi.org/10.1161/01.RES.87.1.12
  28. Simon AR, Takahashi S, Severgnini M, Fanburg BL, Cochran BH. Role of the JAK-STAT pathway in PDGF-stimulated proliferation of human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 282: L1296-304, 2002 https://doi.org/10.1152/ajplung.00315.2001
  29. Sundaresan M, Yu ZK, Ferrans VJ, Irani K, Finkel T. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270: 296-299, 1995 https://doi.org/10.1126/science.270.5234.296
  30. Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N, Griendling KK. p22phox is a critical component of the superoxide-generating NADH/NADPH oxidase system and regulates angiotensin II-induced hypertrophy in vascular smooth muscle cells. J Biol Chem 271: 23317-23321, 1996 https://doi.org/10.1074/jbc.271.38.23317
  31. Vendrov AE, Madamanchi NR, Hakim ZS, Rojas M, Runge MS. Thrombin and NAD(P)H oxidase-mediated regulation of CD44 and BMP4-Id pathway in VSMC, restenosis, and atherosclerosis. Circ Res 98: 1254-1263, 2006 https://doi.org/10.1161/01.RES.0000221214.37803.79
  32. Vasquez-Vivar J, Kalyanaraman B, Martasek P. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 95: 9220-9225, 1998
  33. Wang YZ, Wharton W, Garcia R, Kraker A, Jove R, Pledger WJ. Activation of Stat3 preassembled with platelet-derived growth factor beta receptors requires Src kinase activity. Oncogene 19: 2075-2085, 2000 https://doi.org/10.1038/sj.onc.1203548
  34. White CR, Darley-Usmar V, Berrington WR. Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. Proc Natl Acad Sci USA 93: 8745- 8749, 1996
  35. Yu HM, Zhi JL, Cui Y, Tang EH, Sun SN, Feng JQ, Chen PX. Role of the JAK-STAT pathway in protection of hydrogen peroxide preconditioning against apoptosis induced by oxidative stress in PC12 cells. Apoptosis 11: 931-941, 2006 https://doi.org/10.1007/s10495-006-6578-9
  36. Zalba G, Beaumont FJ, San Jose G, Fortuno A, Fortuno MA, Stayo JC, Diez J. Vascualr NADH＞NADPH oxidase is involved in enhanced superoxide production in spontaneously hypertensive rats. Hypertension 35: 1055-1061, 2000 https://doi.org/10.1161/01.HYP.35.5.1055