본문 바로가기
KERD
논문KCI 등재

Proteasome inhibitors attenuated cholesterol-induced cardiac hypertrophy in H9c2 cells

2

조회

0

다운로드

1

인용

0

참고문헌

키워드

주제분류화학

초록

The Ubiquitin proteasome system (UPS) plays roles in protein degradation, cell cycle control, and growth and inflammatory cell signaling. Dysfunction of UPS in cardiac diseases has been seen in many studies. Cholesterol acts as an inducer of cardiac hypertrophy. In this study, the effect of proteasome inhibitors on the cholesterol-induced hypertrophic growth in H9c2 cells is examined in order to observe whether UPS is involved in cardiac hypertrophy. The treatment of proteasome inhibitors MG132 and Bortezomib markedly reduced cellular surface area and mRNA expression of -MHC in cholesterol-induced cardiac hypertrophy. In addition, activated AKT and ERK were significantly attenuated by MG132 and Bortezomib in cholesterol- induced cardiac hypertrophy. We demonstrated that cholesterol- induced cardiac hypertrophy was suppressed by proteasome inhibitors. Thus, regulatory mechanism of cholesterol- induced cardiac hypertrophy by proteasome inhibitors may provide a new therapeutic strategy to prevent the progression of heart failure.

Abstract

The Ubiquitin proteasome system (UPS) plays roles in protein degradation, cell cycle control, and growth and inflammatory cell signaling. Dysfunction of UPS in cardiac diseases has been seen in many studies. Cholesterol acts as an inducer of cardiac hypertrophy. In this study, the effect of proteasome inhibitors on the cholesterol-induced hypertrophic growth in H9c2 cells is examined in order to observe whether UPS is involved in cardiac hypertrophy. The treatment of proteasome inhibitors MG132 and Bortezomib markedly reduced cellular surface area and mRNA expression of -MHC in cholesterol-induced cardiac hypertrophy. In addition, activated AKT and ERK were significantly attenuated by MG132 and Bortezomib in cholesterol- induced cardiac hypertrophy. We demonstrated that cholesterol- induced cardiac hypertrophy was suppressed by proteasome inhibitors. Thus, regulatory mechanism of cholesterol- induced cardiac hypertrophy by proteasome inhibitors may provide a new therapeutic strategy to prevent the progression of heart failure.

참고문헌 (36)

  1. Frey N, "Hypertrophy of the heart: a new therapeutic target?", Circulation, 109, pp.1580~1589 (2004)
  2. Glenn DJ, "Atrial natriuretic peptide suppresses endothelin gene expression, proliferation in cardiac fibroblasts through a GATA4-dependent mechanism", Cardiovasc Res, 84, pp.209~217 (2009)
  3. 엄광현, "Role of histone deacetylase 2 and its posttranslational modifications in cardiac hypertrophy", BMB Reports, 48(3), pp.131~138 (2015), 생화학분자생물학회
  4. Glickman MH, "The ubiquitinproteasome proteolytic pathway: destruction for the sake of construction", Physiol Rev, 82, pp.373~428 (2002)
  5. Hershko A, "The ubiquitin system", Annu Rev Biochem, 67, pp.425~479 (1998)
  6. Voges D, "The 26S proteasome:a molecular machine designed for controlled proteolysis", Annu Rev Biochem, 68, pp.1015~1068 (1999)
  7. Birks EJ, "Elevated p53 expression is associated with dysregulation of the ubiquitin-proteasome system in dilated cardiomyopathy", Cardiovasc Res, 79, pp.472~480 (2008)
  8. Powell SR, "Oxidized, ubiquitinated proteins may predict recovery of postischemic cardiac function: essential role of the proteasome", Antioxid Redox Signal, 7, pp.538~546 (2005)
  9. Depre C, "Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy", Circulation, 17, pp.1821~1828 (2006)
  10. Bahrudin U, "Ubiquitin-proteasome system impairment caused by a missense cardiac myosin-binding protein C mutation, associated with cardiac dysfunction in hypertrophic cardiomyopathy", J Mol Biol, 384, pp.896~907 (2008)
  11. Oliver MF, "Fatty acids, recovery during first hours of acute myocardial ischemia", Am J Cardiol, 113, pp.285~286 (2014)
  12. Ding Q, "Proteasome inhibition induces reversible impairments in protein synthesis", FASEB J, 8, pp.1055~1063 (2006)
  13. Doll D, "Proteomic expression analysis of cardiomyocytes subjected to proteasome inhibition", Biochem Biophys Res Commun, 2, pp.436~442 (2007)
  14. Kisselev AF, "Proteasome inhibitors:from research tools to drug candidates", Chem Biol, 8, pp.739~758 (2001)
  15. Meiners S, "Downregulation of matrix metalloproteinases, collagens, suppression of cardiac fibrosis by inhibition of the proteasome", Hypertension, 4, pp.471~477 (2004)
  16. Meiners S, "Suppression of cardiomyocyte hypertrophy by inhibition of the ubiquitin-proteasome system", Hypertension, 2, pp.302~308 (2008)
  17. Schlossarek S, "Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy", Front Physiol, 5, pp.484~ (2014)
  18. Stansfield WE, "Proteasome inhibition promotes regression of left ventricular hypertrophy", Am J Physiol Heart Circ Physiol, 2, pp.645~650 (2008)
  19. Kedi X, "Free cholesterol overloading induced smooth muscle cells death, activated both ER-, mitochondrial-dependent death pathway", Atherosclerosis, 207, pp.123~130 (2009)
  20. Rong JX, "Trans differentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading", Proc Natl Acad Sci U S A, 100, pp.13531~13536 (2003)
  21. Lee H, "Cholesterol induces cardiac hypertrophy by activating the AKT pathway", J Steroid Biochem Mol Biol, 138, pp.307~313 (2013)
  22. Liu B, "Compensatory renal hypertrophy is mediated by a cell cycle-dependent mechanism", Kidney Int, 62, pp.1650~1658 (2002)
  23. Siddiqi S, "The heart : mostly postmitotic or mostly premitotic? Myocyte cell cycle, senescence, , quiescence", Can J Cardiol, 30, pp.1270~1278 (2014)
  24. Dreger H, "Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection", Cardiovasc Res, 83, pp.354~361 (2009)
  25. Lüss H, "A proteasome inhibitor confers cardioprotection", Cardiovasc Res, 54, pp.140~151 (2002)
  26. Li N, "Activation of the cardiac proteasome promotes angiotension II-induced hypertrophy by down-regulation of ATRAP", J Mol Cell Cardiol, 79, pp.303~314 (2015)
  27. Weeks KL, "The athlete's heart vs. the failing heart: can signaling explain the two distinct outcomes?", Physiology, 26, pp.97~105 (2011)
  28. Chen B, "MG132, a proteasome inhibitor, attenuates pressure-overload-induced cardiac hypertrophy in rats by modulation of mitogen-activated protein kinase signals", Acta Biochim Biophys Sin, 42, pp.253~258 (2010)
  29. Hsieh V, "Cellular cholesterol regulates ubiquitination, degradation of the cholesterol export proteins ABCA1, ABCG1", J Biol Chem, 289, pp.7524~7536 (2014)
  30. Macías-Vidal J, "The proteasome inhibitor bortezomib reduced cholesterol accumulation in fibroblasts from Niemann-Pick type C patients carrying missense mutations", FEBS J, 281, pp.4450~4466 (2014)
  31. Meiners S, "Proteasome inhibitors: poisons, remedies", Med Res Rev, 28, pp.309~327 (2008)
  32. Blagosklonny MV, "Cell senescence: hypertrophic arrest beyond the restriction point", J Cell Physiol, 209, pp.592~597 (2006)
  33. Busk PK, "Involvement of cyclin D activity in left ventricle hypertrophy in vivo, in vitro", Cardiovasc Res, 1, pp.64~75 (2002)
  34. Gavilán E, "Breast cancer cell line MCF7 escapes from G1", S arrest induced by proteasome inhibition through a GSK-3 dependent mechanism, 2015, pp.5, 10027~
  35. Masamha CP, "Cyclin D1 degradation is sufficient to induce G1 cell cycle arrest despite constitutive expression of cyclin E2 in ovarian cancer cells", Cancer Res, 69, pp.6565~6572 (2009)
  36. Lifang Hu, "Knockdown of microtubule actin crosslinking factor 1 inhibits cell proliferation in MC3T3-E1 osteoblastic cells", BMB Reports, 48(10), pp.583~588 (2015), 생화학분자생물학회

관련 논문AI추천

이 간행물의 다른 논문 (10건)