Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection.
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 alpha-tocopheryl succinate (alpha-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 alpha-TOS, and a mitochondrially targeted coenzyme Q analogue also blocked apoptosis triggered by alpha-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.
Alleva
R
R
Rizzoli Orthopaedic Institute, Bologna, Italy.
Tomasetti
M
M
Andera
L
L
Gellert
N
N
Borghi
B
B
Weber
C
C
Murphy
M P
MP
Neuzil
J
J
D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D024505:Tocopherols; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014451:Ubiquinone / Q000502:physiology*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D014451:Ubiquinone; D014810:Vitamin E; D006861:Hydrogen Peroxide; D024505:Tocopherols