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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).
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页码:11689 / 11704
页数:16
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