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http://dx.doi.org/10.5483/BMBRep.2016.49.5.187

Proteasome inhibitors attenuated cholesterol-induced cardiac hypertrophy in H9c2 cells  

Lee, Hyunjung (Molecular Recognition Research Center, Korea Institute of Science and Technology)
Park, Jinyoung (Molecular Recognition Research Center, Korea Institute of Science and Technology)
Kim, Eunice EunKyeong (Biomedical Research Institute, Korea Institute of Science and Technology)
Yoo, Young Sook (Molecular Recognition Research Center, Korea Institute of Science and Technology)
Song, Eun Joo (Molecular Recognition Research Center, Korea Institute of Science and Technology)
Publication Information
BMB Reports / v.49, no.5, 2016 , pp. 270-275 More about this Journal
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 β-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.
Keywords
Brotezomib; Cholesterol-induced cardiac hypertrophy; H9c2 cells; MG132; Proteasome inhibitors;
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Times Cited By KSCI : 2  (Citation Analysis)
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1 Frey N, Katus HA, Olson EN and Hill JA (2004) Hypertrophy of the heart: a new therapeutic target? Circulation 109, 1580-1589   DOI
2 Glenn DJ, Rahmutula D, Nishimoto M et al (2009) Atrial natriuretic peptide suppresses endothelin gene expression and proliferation in cardiac fibroblasts through a GATA4-dependent mechanism. Cardiovasc Res 84, 209-217   DOI
3 Eom GH, Kook H (2015) Role of histone deacetylase 2 and its posttranslational modifications in cardiac hypertrophy. BMB Rep 48, 131-138   DOI
4 Glickman MH and Ciechanover A (2002) The ubiquitinproteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 82, 373-428   DOI
5 Hershko A and Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67, 425-479   DOI
6 Voges D, Zwickl P and Baumeister W (1999) The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem 68, 1015-1068   DOI
7 Birks EJ, Latif N, Enesa K (2008) Elevated p53 expression is associated with dysregulation of the ubiquitin-proteasome system in dilated cardiomyopathy. Cardiovasc Res 79, 472-480   DOI
8 Powell SR, Wang P, Katzeff H et al (2005) Oxidized and ubiquitinated proteins may predict recovery of postischemic cardiac function: essential role of the proteasome. Antioxid Redox Signal 7, 538-546   DOI
9 Depre C, Wang Q, Yan L et al (2006) Activation of the cardiac proteasome during pressure overload promotes ventricular hypertrophy. Circulation 17, 1821-1828   DOI
10 Bahrudin U, Morisaki H, Morisaki T et al (2008) Ubiquitin-proteasome system impairment caused by a missense cardiac myosin-binding protein C mutation and associated with cardiac dysfunction in hypertrophic cardiomyopathy. J Mol Biol 384, 896-907   DOI
11 Oliver MF (2014) Fatty acids and recovery during first hours of acute myocardial ischemia. Am J Cardiol 113, 285-286   DOI
12 Ding Q, Dimayuga E, Markesbery WR and Keller JN (2006) Proteasome inhibition induces reversible impairments in protein synthesis. FASEB J 8, 1055-1063   DOI
13 Doll D, Sarikas A, Krajcik R and Zolk O (2007) Proteomic expression analysis of cardiomyocytes subjected to proteasome inhibition. Biochem Biophys Res Commun 2, 436-442   DOI
14 Kisselev AF and Goldberg AL (2001) Proteasome inhibitors: from research tools to drug candidates. Chem Biol 8, 739-758   DOI
15 Meiners S, Hocher B, Weller A et al (2004) Downregulation of matrix metalloproteinases and collagens and suppression of cardiac fibrosis by inhibition of the proteasome. Hypertension 4, 471-477   DOI
16 Meiners S, Dreger H, Fechner M et al (2008) Suppression of cardiomyocyte hypertrophy by inhibition of the ubiquitin-proteasome system. Hypertension 2, 302-308   DOI
17 Schlossarek S, Singh SR, Geertz B et al (2014) Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy. Front Physiol 5, 484   DOI
18 Stansfield WE, Tang RH, Moss NC et al (2008) Proteasome inhibition promotes regression of left ventricular hypertrophy. Am J Physiol Heart Circ Physiol 2, 645-650   DOI
19 Kedi X, Ming Y, Yongping W et al (2009) Free cholesterol overloading induced smooth muscle cells death and activated both ER- and mitochondrial-dependent death pathway. Atherosclerosis 207, 123-130   DOI
20 Rong JX, Shapiro M, Trogan E and Fisher EA (2003) Trans differentiation of mouse aortic smooth muscle cells to a macrophage-like state after cholesterol loading. Proc Natl Acad Sci U S A 100, 13531-13536   DOI
21 Lee H, Yoo YS, Lee D and Song EJ (2013) Cholesterol induces cardiac hypertrophy by activating the AKT pathway. J Steroid Biochem Mol Biol 138, 307-313   DOI
22 Liu B and Preisig PA (2002) Compensatory renal hypertrophy is mediated by a cell cycle-dependent mechanism. Kidney Int 62, 1650-1658   DOI
23 Siddiqi S and Sussman MA (2014). The heart: mostly postmitotic or mostly premitotic? Myocyte cell cycle, senescence, and quiescence. Can J Cardiol 30, 1270-1278   DOI
24 Dreger H, Westphal K, Weller A et al (2009) Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection. Cardiovasc Res 83, 354-361   DOI
25 Lüss H, Schmitz W and Neumann J (2002) A proteasome inhibitor confers cardioprotection. Cardiovasc Res 54, 140-151   DOI
26 Li N, Wang HX, Han QY et al (2015) Activation of the cardiac proteasome promotes angiotension II-induced hypertrophy by down-regulation of ATRAP. J Mol Cell Cardiol 79, 303-314   DOI
27 Weeks KL and McMullen JR (2011) The athlete's heart vs. the failing heart: can signaling explain the two distinct outcomes? Physiology 26, 97-105   DOI
28 Chen B, Ma Y, Meng R et al (2010) 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, 253-258   DOI
29 Hsieh V, Kim MJ, Gelissen IC et al (2014) Cellular cholesterol regulates ubiquitination and degradation of the cholesterol export proteins ABCA1 and ABCG1. J Biol Chem 289, 7524-7536   DOI
30 Macías-Vidal J, Girós M, Guerrero M et al (2014) The proteasome inhibitor bortezomib reduced cholesterol accumulation in fibroblasts from Niemann-Pick type C patients carrying missense mutations. FEBS J 281, 4450-4466   DOI
31 Meiners S, Ludwig A, Stangl V and Stangl K (2008) Proteasome inhibitors: poisons and remedies. Med Res Rev 28, 309-327   DOI
32 Blagosklonny MV (2006) Cell senescence: hypertrophic arrest beyond the restriction point. J Cell Physiol 209, 592-597   DOI
33 Busk PK, Bartkova J, Strøm CC et al (2002) Involvement of cyclin D activity in left ventricle hypertrophy in vivo and in vitro. Cardiovasc Res 1, 64-75   DOI
34 Gavilán E, Giráldez S, Sánchez-Aguayo I et al (2015) Breast cancer cell line MCF7 escapes from G1/S arrest induced by proteasome inhibition through a GSK-3β dependent mechanism. Sci Rep 5, 10027   DOI
35 Masamha CP and Benbrook DM (2009) Cyclin D1 degradation is sufficient to induce G1 cell cycle arrest despite constitutive expression of cyclin E2 in ovarian cancer cells. Cancer Res 69, 6565-6572   DOI
36 Hu L, Su P, Li R et al (2015) Knockdown of microtubule actin crosslinking factor 1 inhibits cell proliferation in MC3T3-E1 osteoblastic cells. BMB Rep 48, 583-588   DOI