Skip to main content

Stimulation of Mitogen-Activated Protein Kinases ERK-1 and ERK-2 by H2O2 in Vascular Smooth Muscle Cells

  • Chapter

Part of the book series: Progress in Experimental Cardiology ((PREC,volume 3))

Summary

The possible roles of the mitogen-activated protein kinases (MAPKs) ERK-1 and ERK-2 in mediating growth-promoting and hypertrophic responses were investigated by examining the effect of H2O2 on ERK-1 and ERK-2 phosphorylation and activation in an established vascular smooth muscle cell (VSMC) line (A10). H2O2 treatment of VSMCs stimulated the phosphorylation of both ERK-1 and ERK-2 in a concentration-dependent manner with maximal impact at the dose level of 2mM H2O2. Treatment of cells with aminotriazole, an inhibitor of catalase, potentiated the effect of H2O2 and reduced the H2O2 concentration required to elicit the maximum response. In addition, PD98059, an inhibitor of MAPK kinase (MEK), and wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), attenuated the H2O2-induced activation of ERK-1 and ERK-2. H2O2 was also found to stimulate PI3K activity, which was inhibited by wortmannin. Taken together, these data demonstrate that oxidative stress-induced ERK activation is mediated, at least in part, through a PI3K-dependent pathway and suggest a role of this pathway in eliciting growth-promoting and hypertrophic responses to H2O2 in VSMCs.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ames BN, Shigenaga MK, Hagen TM. 1993. Oxidant, antioxi dants and the pathogenesis of degenerative diseases of aging. Proc Nad Acad Sci USA 90:7915–7922.

    Article  CAS  Google Scholar 

  2. Alexander RW. 1995. Hypertension and the pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 25:155–161.

    Article  PubMed  CAS  Google Scholar 

  3. Griendling KK, Mineri CA, Ollerenshaw JD, Alexander RW. 1994. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74:1141–1148.

    Article  PubMed  CAS  Google Scholar 

  4. Ushio-Fukai M, Zafari AM, Fukui T, Ishizaka N, Griendling KK. 1996. P22 phox 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 271:23317–23322.

    Article  PubMed  CAS  Google Scholar 

  5. Fukui T, Ishizaka N, Rajagopalan S, Laursen JB, Capers Q, Taylor WR, Harrison DG, de Leon H, Wilcox JN, Griendling KK. 1997. P22 phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats. Circ Res 80:45–51.

    Article  PubMed  CAS  Google Scholar 

  6. Lu G, Greene EL, Nagui T, Egan BM. 1998. Reactive oxygen species are critical in the oleic acid-mediated signaling pathway in vascular smooth muscle cells. Hypertension 32:1003–1010.

    Article  PubMed  CAS  Google Scholar 

  7. Rao GN, Berk BC. 1992. Active oxygen species stimulate vascular smooth muscle cell growth and protooncogene expression. Circ Res 70:593–599.

    Article  PubMed  CAS  Google Scholar 

  8. Chakraborti S, Chakraborti T. 1998. Oxidant-mediated activation of mitogen-activated protein kinases and nuclear transcription factors in cardiovascular system: a brief overview. Cell Signal 10:675–683.

    Article  PubMed  CAS  Google Scholar 

  9. Kamata H, Hirata H. 1999. Redox regulation of cellular signaling. Cell Signal 11:1–14.

    Article  PubMed  CAS  Google Scholar 

  10. Widmann C, Gibson S, Jarpe MB, Johnson GL. 1999. Mitogen-activated protein kinase: Conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180.

    PubMed  CAS  Google Scholar 

  11. Seger R, Krebs EG. 1995. The MAPK signaling cascade. FASEB J 9:726–735.

    PubMed  CAS  Google Scholar 

  12. Toker A, Cantley LC. 1997. Signaling through the lipid products of phosphoinositide-3-OH-kinase. Nature (Lond) 387:673–676.

    Article  CAS  Google Scholar 

  13. Fruman DA, Meyers RE, Cantley LC. 1998. Phosphoinositide kinase. Annu Rev Biochem 67:481–507.

    Article  PubMed  CAS  Google Scholar 

  14. Vanhaesebroeck B, Stein RC, Waterfield MD. 1996. The study of phosphoinositide function. Cancer Surv 27:249–270.

    PubMed  CAS  Google Scholar 

  15. Saward L, Zahradka P. 1997. Angiotensin II activates phosphatidylinositol 3-kinase in vascular smooth muscle cells. Circ Res 81:249–257.

    Article  PubMed  CAS  Google Scholar 

  16. Cotter PJ, Woodgett JR. 1998. Protein kinase B (c-Akt): a multifunctional mediator of phosphatidylinositol 3-kinase activation. Biochem J 335:1–13.

    Google Scholar 

  17. Cohen P, Alessi DR, Cross DAE. 1997. PDK1, one of the missing links in insulin signal transduction. FEBS Lett 410:3–10.

    Article  PubMed  CAS  Google Scholar 

  18. Cross DAE, Alessi DR, Vandenheede JR, McDowell HE, Hundal HS, Cohen P. 1994. The inhibition of glycogen synthase kinase-3 by insulin or insulin-like growth factor 1 in the rat skeletal muscle cell line L6 is blocked by wortmannin but not repamycin: Evidence that wortmannin blocks activation of the mitogen-activated protein kinase pathway between ras and raf. Biochem J 303:21–26.

    PubMed  CAS  Google Scholar 

  19. Hurel SJ, Rochford JJ, Borthwick AC, Wells AM, Vandenheede JR, Turnbull DM, Yeaman SJ. 1996. Insulin action in cultured human myoblasts: contribution of different signaling pathways to regulate glycogen synthesis. Biochem J 320:871–877.

    PubMed  CAS  Google Scholar 

  20. Welsh GI, Foulstone EJ, Young SW, Tavare JM, Proud CG. 1994. Wortmannin inhibits the effects of insulin and serum on the activities of glycogen synthase kinase-3 and mitogen-activated protein kinase. Biochem J 303:15–20.

    PubMed  CAS  Google Scholar 

  21. Uehara T, Tokumitsu Y, Nomura Y. 1995. Wortmannin inhibits insulin-induced ras and mitogen-activated protein kinase activation related to adipocyte differentiation in 3T3-L1 fibroblasts. Biochem Biophys Res Commun 210:574–580.

    Article  PubMed  CAS  Google Scholar 

  22. Standaert ML, Bandyopadhayay G, Farese RV. 1995. Studies with wortmannin suggest a role for phosphatidylinositol 3-kinase in the activation of glycogen synthase and mitogen-activated protein kinase by insulin rat adipocytes: comparison of insulin and protein kinase C modulators. Biochem Biophys Res Commun 209:1082–1088.

    Article  PubMed  CAS  Google Scholar 

  23. Fialkow L, Chan CK, Rotin D, Grinstein S, Downey GP. 1994. Activation of mitogenactivated protein kinase signaling pathway in neutrophils: role of oxidants. J Biol Chem 269:31234–31242.

    PubMed  CAS  Google Scholar 

  24. Guyton KZ, Liu Y, Gorospe M, Xu Q, Holbrook NJ. 1996. Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem 271:4138–4142.

    Article  PubMed  CAS  Google Scholar 

  25. Samanta S, Perkinton MS, Morgan M, Williams RJ. 1998. Hydrogen peroxide enhances signal-responsive arachidonic acid release from neurons: role of mitogen-activated protein kinase. J Neurochem 70:2082–2090.

    Article  PubMed  CAS  Google Scholar 

  26. Servant MJ, Giasson E, Meloche S. 1996. Inhibition of growth factor induced protein synthesis by a selective MEK inhibitor in aortic smooth muscle cells. J Biol Chem 271:16047–16052.

    Article  PubMed  CAS  Google Scholar 

  27. Ushio-Fukai M, Alexander RW, Akers M, Griendling KK. 1998. P38 mitogen-activated protein kinase is a critical component of the radox-sensitive signaling pathways activated by angiotensin II. Role in vascular smooth muscle cell hypertrophy. J Biol Chem 273:15022–15029.

    Article  PubMed  CAS  Google Scholar 

  28. Baas AS, Berk BC. 1995. Differential activation of mitogen-activated protein kinases by H2O2 and O2 in vascular smooth muscle cell. Circ Res 77:29–36.

    Article  PubMed  CAS  Google Scholar 

  29. Abe J-I, Kusuhara M, Ulevitch RJ, Berk BC, Lee J-D. 1996. Big mitogen-activated protein kinase 1 (BMK1) is a redox-sensitive kinase. J Biol Chem 271:16586–16590.

    Article  PubMed  CAS  Google Scholar 

  30. Kimes BW, Brandt BL. 1976. Characterization of two putative smooth muscle cell lines from rat thoracic aorta. Exp Cell Res 98:349–366.

    Article  PubMed  CAS  Google Scholar 

  31. Lutz W, Sanders M, Salisbury J, Kumar R. 1990. Internalization of vasopressin analogs in kidney and smooth muscle cells: evidence for receptor-mediated endocytosis in cells with V2 and V1 receptors. Proc Natl Acad Sci USA 87:6507–6511.

    Article  PubMed  CAS  Google Scholar 

  32. Muldoon LL, Rodland KD, Forsythe ML, Magun BE. 1989. Stimulation of phosphatidylinositol hydrolysis, diacylglycerol release, and gene expression in response to endothelin, a potent new agonist for fibroblasts and smooth muscle cells. J Biol Chem 264:8529–8536.

    PubMed  CAS  Google Scholar 

  33. Tan CM, Xenoyannis S, Feldman RD. 1995. Oxidant stress enhances adenylyl cyclase activation. Circ Res 77:710–717.

    Article  PubMed  CAS  Google Scholar 

  34. Pandey SK, Anand-Srivastava MB, Srivastava AK. 1998. Vanadyl sulfate-stimulated glycogen synthesis is associated with activation of phosphatidylinositol 3-kinase and is independent of insulin receptor tyrosine phosphorylation. Biochemistry 37:7006–7014.

    Article  PubMed  CAS  Google Scholar 

  35. Palaparti A, Anand-Srivastava MB. 1996. Modulation of ANF-R2/ANP-C receptors by angiotensin II in vascular smooth muscle cells. Am J Hypertens 9:930–934.

    Article  PubMed  CAS  Google Scholar 

  36. Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR. 1995. PD98059 is a specific inhibitor of the activation of mitogen activated protein kinase kinase in vitro and in vivo. J Biol Chem 270:27489–27494.

    Article  PubMed  CAS  Google Scholar 

  37. Knall C, Young S, Nick JA, Buhl AM, Worthen GS, Johnson GL. 1996. Interleukin-8 regulation of the ras/raf/mitogen-activated protein kinase pathway in human neutrophils. J Biol Chem 271:2832–2838.

    Article  PubMed  CAS  Google Scholar 

  38. Karnitz LM, Burns LA, Sutor SL, Blenis J, Abraham RT. 1995. Interleukin-2 triggers a novel phosphatidylinositol 3-kinase-dependent MEK activation pathway. Mol Cell Biol 15:3049–3057.

    PubMed  CAS  Google Scholar 

  39. Ui M, Okada T, Hazeki K, Hazeki O. 1995. Wortmannin as a unique probe for an intracellular signaling protein, phosphoinositol 3-kinase. Trends Biochem Sci 20:303–307.

    Article  PubMed  CAS  Google Scholar 

  40. Clerk A, Fuller SJ, Michael A, Sugden PH. 1998. Stimulation of “stress-regulated” mitogen-activated protein kinases (stress-activated protein kinases/c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in perfused rat hearts by oxidative and other stresses. J Biol Chem 273:7228–7234.

    Article  PubMed  CAS  Google Scholar 

  41. Aikawa R, Komuro I, Yamazaki T, Zou Y, Kudoh S, Tanaka M, Shiojima I, Hiroi Y, Yazaki Y. 1997. Oxidative stress activates extracellular signal regulated kinases through src and ras in cultured cardiac myocytes of neonatal rats. J Clin Invest 100:1813–1821.

    Article  PubMed  CAS  Google Scholar 

  42. Abe MK, Kartha S, Karpova AY, Li J, Liu PT, Kuo W-L, Hershenson MB. 1998. Hydrogen peroxide activates extracellular signal-regulated kinase via protein kinase C, raf-1 and MEK-1. Am J Respir Cell Mol Biol 18:562–569.

    PubMed  CAS  Google Scholar 

  43. Stone RL, Dixon JE. 1994. Protein tyrosine phosphatases. J Biol Chem 269:31323–31326.

    PubMed  CAS  Google Scholar 

  44. Wu Y, Kwon K-S, Rhe SG. 1998. Probing cellular protein targets of H2O2 with fluorescein-conjugated iodoacetamide and antibodies to fluorescein. FEBS Lett 440:111–115.

    Article  PubMed  CAS  Google Scholar 

  45. Hecht D, Zick Y. 1992. Selective inhibition of protein tyrosine phosphatase activity by H2O2 and vanadate in vitro. Biochem Biophys Res Commun 188:773–778.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media New York

About this chapter

Cite this chapter

Srivastava, A.K., Pandey, S.K. (2000). Stimulation of Mitogen-Activated Protein Kinases ERK-1 and ERK-2 by H2O2 in Vascular Smooth Muscle Cells. In: Takeda, N., Nagano, M., Dhalla, N.S. (eds) The Hypertrophied Heart. Progress in Experimental Cardiology, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4423-4_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-4423-4_16

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6991-2

  • Online ISBN: 978-1-4615-4423-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics