title: Coenzyme Q10 rescues ethanol-induced corneal fibroblast apoptosis through the inhibition of caspase-2 activation.
abstract: 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 Q10 (CoQ10) 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 CoQ10 prevented EtOH-induced caspase-2 activation and mitochondria-mediated apoptosis. Our data demonstrated that by blocking caspase-2 activity, CoQ10 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 CoQ10.
authors: Department of Ophthalmology, Taipei City Hospital Renai Branch, Taipei, Taiwan 106.
authors: Chun-Chen
authors: CC
authors: Chen
authors: Shiow-Wen
authors: SW
authors: Liou
authors: Chi-Chih
authors: CC
authors: Chen
authors: Wen-Chung
authors: WC
authors: Chen
authors: Fung-Rong
authors: FR
authors: Hu
authors: I-Jong
authors: IJ
authors: Wang
authors: Shing-Jong
authors: SJ
authors: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053143:Caspase 2 / Q000378:metabolism*; D053148:Caspase 3 / Q000096:biosynthesis; D002417:Cattle; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D012997:Solvents; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D014451:Ubiquinone; D000431:Ethanol; D053143:Caspase 2; D053148:Caspase 3; C024989:coenzyme Q10