Coenzyme Q10 Rescues Ethanol-induced Corneal Fibroblast Apoptosis through the Inhibition of Caspase-2 Activation

被引:15
作者
Chen, Chun-Chen [1 ,2 ]
Liou, Shiow-Wen [1 ,6 ,7 ]
Chen, Chi-Chih [4 ]
Chen, Wen-Chung [4 ]
Hu, Fung-Rong [6 ]
Wang, I-Jong [6 ,8 ]
Lin, Shing-Jong [2 ,3 ,5 ]
机构
[1] Taipei City Hosp Renai Branch, Dept Ophthalmol, Taipei 106, Taiwan
[2] Natl Yang Ming Univ, Inst Clin Med, Taipei 112, Taiwan
[3] Natl Yang Ming Univ, Cardiovasc Res Ctr, Taipei 112, Taiwan
[4] Taipei Vet Gen Hosp, Dept Internal Med, Div Cardiol, Taipei 112, Taiwan
[5] Taipei Vet Gen Hosp, Dept Med Res & Educ, Taipei 112, Taiwan
[6] Natl Taiwan Univ Hosp, Dept Ophthalmol, Taipei 100, Taiwan
[7] Taipei Med Univ, Taipei 110, Taiwan
[8] China Med Univ, Grad Inst Clin Med Sci, Taichung 404, Taiwan
关键词
STRESS-INDUCED APOPTOSIS; MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C RELEASE; OXIDATIVE DNA-DAMAGE; CELL-DEATH; CAENORHABDITIS-ELEGANS; IN-VITRO; ALCOHOL; UBIQUINONE; PATHWAYS;
D O I
10.1074/jbc.M112.401844
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent studies indicate that caspase-2 is involved in the early stages of apoptosis, particularly before the occurrence of mitochondrial damage. Here we report the important role of the coenzyme Q(10) (CoQ(10)) on the activity of caspase-2 upstream of mitochondria in ethanol (EtOH)-treated corneal fibroblasts. After EtOH exposure, cells produce excessive reactive oxygen species formation, p53 expression, and most importantly, caspase-2 activation. After the activation of the caspase-2, the cells exhibited hallmarks of apoptotic pathway, such as mitochondrial damage and translocation of Bax and cytochrome c, which were then followed by caspase-3 activation. By pretreating the cells with a cell-permeable, biotinylated pan-caspase inhibitor, we identified caspase-2 as an initiator caspase in EtOH-treated corneal fibroblasts. Loss of caspase-2 inhibited EtOH-induced apoptosis. We further found that caspase-2 acts upstream of mitochondria to mediate EtOH-induced apoptosis. The loss of caspase-2 significantly inhibited EtOH-induced mitochondrial dysfunction, Bax translocation, and cytochrome c release from mitochondria. The pretreatment of CoQ(10) prevented EtOH-induced caspase-2 activation and mitochondria-mediated apoptosis. Our data demonstrated that by blocking caspase-2 activity, CoQ(10) can protect the cells from mitochondrial membrane change, apoptotic protein translocation, and apoptosis. Taken together, EtOH-induced mitochondria-mediated apoptosis is initiated by caspase-2 activation, which is regulated by CoQ(10).
引用
收藏
页码:11689 / 11704
页数:16
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