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

FEBS Letters

Alleva, Renata¹  Gellert, Nina⁵  Weber, Christian⁵  Borghi, Battista¹  Andera, Ladislav³  Tomasetti, Marco⁴  Neuzil, Jiri⁵  Murphy, Michael P.² 

[1] Rizzoli Orthopaedic Institute, Bologna, Italy;Mitochondrial Dysfunction Group, MRC Dunn Human Nutrition Unit, Cambridge, UK;Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic;Institute of Experimental Pathology, University of Ancona, Ancona, Italy;Institute for Prevention of Cardiovascular Diseases, Ludwig Maximilians University, Pettenkoferstrasse 9, 80336 Munich, Germany

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;   

DOI  :  10.1016/S0014-5793(01)02694-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown