Coenzyme Q protects cells against serum withdrawal-induced apoptosis by inhibition of ceramide release and caspase-3 activation.
Coenzyme Q10 (CoQ10) is a component of the antioxidant machinery that protects cell membranes from oxidative damage and decreases apoptosis in leukemic cells cultured in serum-depleted media. Serum deprivation induced apoptosis in CEM-C7H2 (CEM) and to a lesser extent in CEM-9F3, a subline overexpressing Bcl-2. Addition of CoQ10 to serum-free media decreased apoptosis in both cell lines. Serum withdrawal induced an early increase of neutral-sphingomyelinase activity, release of ceramide, and activation of caspase-3 in both cell lines, but this effect was more pronounced in CEM cells. CoQ10 prevented activation of this cascade of events. Lipids extracted from serum-depleted cultures activated caspase-3 independently of the presence of mitochondria in cell-free in vitro assays. Activation of caspase-3 by lipid extracts or ceramide was prevented by okadaic acid, indicating the implication of a phosphatase in this process. Our results support the hypothesis that plasma membrane CoQ10 regulate the initiation phase of serum withdrawal-induced apoptosis by preventing oxidative damage and thus avoiding activation of downstream effectors as neutral-sphingomyelinase and subsequent ceramide release and caspase activation pathways.
Laboratorio Andaluz de Biología, Universidad Pablo de Olavide, Sevilla, Spain.
D J
DJ
Fernández-Ayala
S F
SF
Martín
M P
MP
Barroso
C
C
Gómez-Díaz
J M
JM
Villalba
J C
JC
Rodríguez-Aguilera
G
G
López-Lluch
P
P
Navas
D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D002462:Cell Membrane / Q000378:metabolism; D002474:Cell-Free System; D002518:Ceramides / Q000037:antagonists & inhibitors*; D003067:Coenzymes; D016895:Culture Media, Serum-Free; D003576:Electron Transport Complex IV / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D050356:Lipid Metabolism; D008928:Mitochondria / Q000378:metabolism; D019319:Okadaic Acid / Q000378:metabolism; D018384:Oxidative Stress; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000378:metabolism*
D061945:Caspase Inhibitors; D002518:Ceramides; D003067:Coenzymes; D016895:Culture Media, Serum-Free; D014451:Ubiquinone; D019319:Okadaic Acid; D003576:Electron Transport Complex IV; D013108:Sphingomyelin Phosphodiesterase; C505407:CASP3 protein, human; D053148:Caspase 3; C024989:coenzyme Q10