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Coenzyme Q blocks biochemical but not receptor‐mediated apoptosis by increasing mitochondrial antioxidant protection
[摘要]

Generation of free radicals is often associated with the induction and progression of apoptosis. Therefore, antioxidants can prove anti-apoptotic, and can help to elucidate specific apoptotic pathways. Here we studied whether coenzyme Q, present in membranes in reduced (ubiquinol) or oxidised (ubiquinone) forms, can affect apoptosis induced by various stimuli. Exposure of Jurkat cells to α-tocopheryl succinate (α-TOS), hydrogen peroxide, anti-Fas IgM or TRAIL led to induction of apoptosis. Cell death due to the chemical agents was suppressed in cells enriched with the reduced form of coenzyme Q. However, coenzyme Q did not block cell death induced by the immunological agents. Ubiquinol-10 inhibited reactive oxygen species (ROS) generation in cells exposed to α-TOS, and a mitochondrially targeted coenzyme Q analogue also blocked apoptosis triggered by α-TOS or hydrogen peroxide. Therefore, it is plausible that ubiquinol-10 protects cells from chemically-induced apoptosis by acting as an antioxidant in mitochondria. Our results also indicate that generation of free radicals may not be a critical step in induction of apoptosis by immunological agents.

[发布日期]  [发布机构] 
[效力级别]  [学科分类] 生物化学/生物物理
[关键词] Apoptosis;Signalling;Coenzyme Q;Reactive oxygen species;Lymphoma cell;CoQ10;oxidised coenzyme Q10;CoQ10H2;reduced coenzyme Q10;DCFH-DA;2′;7′-dichlorodihydrofluorescein diacetate;FACS;fluorescence-assisted cell sorting;JC-1;5;5′;6;6′-tetrachloro-1;1′;3;3′-tetraethyl-benzimidoazoyl-carbocyanino iodide;PS;phosphatidyl serine;ROS;reactive oxygen species;α-TOS;α-tocopheryl succinate;TRAIL;TNF-related apoptosis-inducing ligand;ΔΨ m;mitochondrial inner membrane potential [时效性] 
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