CCN1 enables Fas ligand-induced apoptosis in cardiomyoblast H9c2 cells by disrupting caspase inhibitor XIAP

Bor Chyuan Su, Fan E. Mo

研究成果: 雜誌貢獻文章同行評審

14 引文 斯高帕斯(Scopus)

摘要

Cell proliferation from pre-existing cardiomyocytes is a major source of cells for normal mammalian myocardial renewal or for regeneration after myocardial injury. These proliferative cardiomyocytes may act differently from the postmitotic cardiomyocytes in a stressed heart. Extracellular matrix molecule CCN1 is produced to promote Fas ligand (FasL)-induced cardiomyocyte apoptosis in mice with stress-induced cardiac injury. We aimed to investigate the effect of CCN1 on the proliferative cardiomyocytes. We used rat embryonic cardiomyoblast H9c2 cells to study the cardiotoxicity of CCN1. We found that FasL dose-dependently increased the X-linked inhibitor of apoptosis protein (XIAP) levels to prevent the progression of apoptosis in H9c2 cells. CCN1, though it did not induce apoptosis by itself, sensitized H9c2 cells to FasL-induced apoptosis. CCN1 functions by engaging its cell-surface receptor integrin α6β1 and elevating reactive oxygen species levels, which leads to mitogen-activated protein kinase p38 activation, cytosolic Bax translocation to mitochondria, and the release of mitochondrial Smac and HtrA2 to cytosol. These elevated cytosolic Smac and HtrA2 dismantle the inhibition of XIAP, thereby facilitating the activation of caspase-3 and the apoptosis-induced by FasL. In summary, we demonstrated a novel mechanism underlying the resistance of cardiomyoblasts to FasL-induced apoptosis, and the pro-apoptotic function of CCN1 by disrupting this resistance.
原文英語
頁(從 - 到)1326-1334
頁數9
期刊Cellular Signalling
26
發行號6
DOIs
出版狀態已發佈 - 六月 2014

ASJC Scopus subject areas

  • 細胞生物學

指紋

深入研究「CCN1 enables Fas ligand-induced apoptosis in cardiomyoblast H9c2 cells by disrupting caspase inhibitor XIAP」主題。共同形成了獨特的指紋。

引用此