Skip to main content
Log in

Protein kinase C isozymes in hypertension and hypertrophy: Insight from SHHF rat hearts

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Chronic hypertension results in cardiac hypertrophy and may lead to congestive heart failure. The protein kinase C (PKC) family has been identified as a signaling component promoting cardiac hypertrophy. We hypothesized that PKC activation may play a role mediating hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat heart. Six-month-old SHHF and normotensive control Wistar Furth (WF) rats were used. Hypertension and cardiac hypertrophy were confirmed in SHHF rats. PKC expression and activation were analyzed by Western blots using isozyme-specific antibodies. Compared to WF, untreated SHHF rats had increased phospho-active α (10-fold), δ (4-fold), and ε (3-fold) isozyme expression. Furthermore, we analyzed the effect of an angiotensin II type 1 receptor blocker (ARB) and hydralazine (Hy) on PKC regulation in SHHF rat left ventricle (LV). Both the ARB and Hy normalized LV blood pressure, but only the ARB reduced heart mass. Neither treatment affected PKC expression or activity. Our data show differential activation of PKC in the hypertensive, hypertrophic SHHF rat heart. Regression of hypertrophy elicited by an ARB in this model occurred independently of changes in the expression and activity of the PKC isoforms examined. (Mol Cell Biochem 270: 63–69, 2005)

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jalili T, Takeishi Y, Walsh RA: Signal transduction during cardiac hypertrophy: the role of Gα q , PLC βI, and PKC. Cardiovasc Res 44: 5–9, 1999

    Google Scholar 

  2. Bowling N, Walsh RA, Song G, Estridge T, Sandusky GE, Fouts RL, et al.: Increased protein kinase C activity and expression of Ca2+-sensitive isoforms in the failing human heart. Circulation 99: 384–391, 1999

    Google Scholar 

  3. Wang J, Liu X, Sentex E, Takeda N, Dhalla NS: Increased expression of protein kinase C isoforms in heart failure due to myocardial infarction. Am J Physiol Heart Circ Physiol 284:H2277–H2287, 2003

    Google Scholar 

  4. Braz JC, Gregory K, Pathak A, Zhao W, Sahin B, Klevitsky R, et al.: PKC α regulates contractility and propensity toward heart failure. Nat Med 10: 248–254, 2004

    Google Scholar 

  5. Naruse K, King GL: Protein kinase C and myocardial biology and function. Circ Res 86: 1104–1106, 2000

    Google Scholar 

  6. Dempsey EC, Newton AC, Mochly-Rosen D, Fields AP, Reyland ME, Insel PA, et al.: Protein kinase C isozymes and the regulation of diverse cell responses. Am J Physiol Lung Cell Mol Physiol 279: L429–L438, 2000

    Google Scholar 

  7. Ping P: A new chapter in cardiac PKC signaling studies: Searching for isoform-specific molecular targets. Focus on: “Isoenzyme-selective regulation of SERCA2 gene expression by protein kinase C in neonatal rat ventricular myocytes”. Am J Physiol Cell Physiol 285: C19–C21, 2003

    Google Scholar 

  8. Pucéat M, Hilal-Dandan R, Strulovici B, Brunton LL, Brown JH: Differential regulation of protein kinase C isoforms in isolated neonatal and adult rat cardiomyocytes. J Biol Chem 269: 16938–16944, 1994

    Google Scholar 

  9. Mochly-Rosen D, Wu G, Hahn H, Osinska H, Liron T, Lorenz JN, et al.: Cardiotrophic effects of protein kinase C ε. Analysis by in vivo modulation of PKCε translocation. Circ Res 86: 1173–1179, 2000

    Google Scholar 

  10. Parekh DB, Ziegler W, Parker PJ: Multiple pathways control protein kinase C phosphorylation. EMBO J 19: 496–503, 2000

    Google Scholar 

  11. Heyen JR, Blasi ER, Nikula K, Rocha R, Daust HA, Frierdich G, et al.: Structural, functional, and molecular characterization of the SHHF model of heart failure. Am J Physiol Heart Circ Physiol 283: H1775–H1784, 2002

    Google Scholar 

  12. Gerdes AM, Onodera T, Wang X, McCune SA: Myocyte remodeling during the progression to failure in rats with hypertension. Hypertension 28: 609–614, 1996

    Google Scholar 

  13. Kacimi R, Gerdes AM: Alterations in G protein and MAP kinase signaling pathways during cardiac remodeling in hypertension and heart failure. Hypertension 41: 968–977, 2003

    Google Scholar 

  14. Anderson KM, Eckhart AD, Willette RN, Koch WJ: The myocardial β-adrenergic system in spontaneously hypertensive heart failure (SHHF) rats. Hypertension 33: 402–407, 1999

    Google Scholar 

  15. Chang RS, Siegl PK, Clineschmidt BV, et al.: In vivo pharmacology of L-158,809, a new highly potent and selective angiotensin II receptor antagonist. J Pharmacol Exp Ther 262: 133–138, 1992

    Google Scholar 

  16. Ron D, Kazanietz MG: New insights into the regulation of protein kinase C and novel phorbol ester receptors. FASEB J 13: 1658–1676, 1999

    Google Scholar 

  17. Hahn HS, Yussman MG, Toyokawa T, Marreez Y, Barrett TJ, Hilty KC, et al.: Ischemic protection and myofibrillar cardiomyopathy. Dose-dependent effects of in vivo δPKC inhibition. Circ Res 91: 741–748, 2002

    Article  CAS  PubMed  Google Scholar 

  18. Takeishi Y, Ping P, Bolli R, Kirkpatrick DL, Hoit BD, Walsh RA: Transgenic overexpression of constitutively active protein kinase C ε causes concentric cardiac hypertrophy. Circ Res 86: 1218–1223, 2000

    CAS  PubMed  Google Scholar 

  19. Kerkela R, Ilves M, Pikkarainen S, Tokola H, Ronkainen J, Vuolteenaho O, et al.: Identification of PKCα isoform-specific effects in cardiac myocytes using antisense phosphorothioate oligonucleotides. Mol Pharmacol 62: 1482–1491, 2002

    Google Scholar 

  20. Clerk A, Sugden PH: Untangling the web. Specific signaling from PKC isoforms to MAPK cascades. Circ Res 89: 847–849, 2001

    Google Scholar 

  21. Akita Y: Protein kinase C-ε (PKC-ε): Its unique structure and function. J Biochem 132: 847–852, 2002

    Google Scholar 

  22. Wu G, Toyokawa T, Hahn H, Dorn GW: ε Protein kinase C in pathologic myocardial hypertrophy. J Biol Chem 275: 29927–29930, 2000

    Google Scholar 

  23. Inagaki K, Iwanaga Y, Sarai N, Onozawa Y, Takenda H, Mochly-Rosen D, et al.: Tissue angiotensin II during progression or ventricular hypertrophy to heart failure in hypertensive rats; differential effects on PKCε and PKCβ. J Mol Cell Cardiol 34: 1377–1385, 2002

    Google Scholar 

  24. Onodera T, Tamura T, Said S, McCune SA, Gerdes AM: Maladaptive remodeling of cardiac myocyte shape begins long before failure in hypertension. Hypertension 32: 753–757, 1998

    Google Scholar 

  25. Bayer AL, Heidkamp MC, Patel N, Porter M, Engman S, Samarel AM: Alterations in protein kinase C isoenzyme expression and autophosphorylation during the progression of pressure overload-induced left ventricular hypertrophy. Mol Cell Biochem 242: 145–152, 2003

    Google Scholar 

  26. Simonis G, Honold J, Schwarz K, Braun MU, Strasser RH: Regulation of the isozymes of protein kinase C in the surviving rat myocardium after myocardial infarction: Distinct modulation for PKC-α and for PKC-δ. Basic Res Cardiol 97: 223–231, 2002

    Google Scholar 

  27. Rybin VO, Steinberg SF: Protein kinase C isoform expression and regulation in the developing rat heart. Circ Res 74: 229–309, 1994

    Google Scholar 

  28. Takeishi Y, Jalili T, Ball NA, Walsh RA: Responses of cardiac protein kinase C isoforms to distinct pathological stimuli are differentially regulated. Circ Res 85: 264–271, 1999

    CAS  PubMed  Google Scholar 

  29. Sadoshima J, Izumo S: Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Critical role of the AT1 receptor subtype. Circ Res 73: 413–423, 1993

    CAS  PubMed  Google Scholar 

  30. Sadoshima J, Xu Y, Slayter HS, Izumo S: Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75: 977–984, 1993

    Google Scholar 

  31. Harada K, Issei K, Shiojima I, Hayashi D, Kudoh S, Mizuno T, et al.: Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor knockout mice. Circulation 97: 1952–1959, 1998

    Google Scholar 

  32. Kudoh S, Komuro I, Hiroi Y, Zou Y, Harada K, Sugaya T, et al.: Mechanical stretch induces hypertrophic responses in cardiac myocytes of angiotensin II type 1A receptor knockout mice. J Biol Chem 273: 24037–24043, 1998

    Google Scholar 

  33. Paul K, Ball NA, Dorn GW, Walsh RA: Left ventricular stretch stimulates angiotensin II-mediated phosphatidylinositol hydrolysis and protein kinase C ε isoform translocation in adult guinea pig hearts. Circ Res 81: 643–650, 1997

    Google Scholar 

  34. Sabri A, Steinberg SF: Protein kinase C isoform-selective signals that lead to cardiac hypertrophy and the progression of heart failure. Mol Cell Biochem 251: 97–101, 2003

    Google Scholar 

  35. Tamura T, Said S, Harris J, Lu W, Gerdes AM: Reverse remodeling of cardiac myocyte hypertrophy in hypertension and failure by targeting of the renin-angiotensin system. Circulation 102: 253–259, 2000

    Google Scholar 

  36. Tamura T, Said S, Andersen SMK, McCune SA, Mochizuki S, Gerdes AM: Temporal regression of myocyte hypertrophy in hypertensive, heart failure-prone rats treated with an AT1-receptor antagonist. J Cardiac Failure 8: 43–47, 2002

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Martin Gerdes.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Johnsen, D.D., Kacimi, R., Anderson, B.E. et al. Protein kinase C isozymes in hypertension and hypertrophy: Insight from SHHF rat hearts. Mol Cell Biochem 270, 63–69 (2005). https://doi.org/10.1007/s11010-005-3781-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-005-3781-x

Key words

Navigation