Role of plasma membrane coenzyme Q on the regulation of apoptosis.
Serum withdrawal is a model to study the mechanisms involved in the induction of apoptosis caused by mild oxidative stress. Apoptosis induced by growth factors removal was prevented by the external addition of antioxidants such as ascorbate, alpha-tocopherol and coenzyme Q (CoQ). CoQ is a lipophilic antioxidant which prevents oxidative stress and participates in the regeneration of alpha-tocopherol and ascorbate in the plasma membrane. We have found an inverse relationship between CoQ content in plasma membrane and lipid peroxidation rates in leukaemic cells. CoQ10 addition to serum-free culture media prevented both lipid peroxidation and cell death. Also, CoQ10 addition decreased ceramide release after serum withdrawal by inhibition of magnesium-dependent plasma membrane neutral-sphingomyelinase. Moreover, CoQ10 addition partially blocked activation of CPP32/caspase-3. These results suggest CoQ of the plasma membrane as a regulator of initiation phase of oxidative stress-mediated serum withdrawal-induced apoptosis.
López-Lluch
G
G
Laboratorio Andaluz de Biología, Universidad Pablo de Olavide, Sevilla, Spain.
Barroso
M P
MP
Martín
S F
SF
Fernández-Ayala
D J
DJ
Gómez-Díaz
C
C
Villalba
J M
JM
Navas
P
P
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology*; D002518:Ceramides / Q000378:metabolism; D016895:Culture Media, Serum-Free; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D015227:Lipid Peroxidation; D008861:Microsomes / Q000378:metabolism; D018384:Oxidative Stress; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism*
D002518:Ceramides; D016895:Culture Media, Serum-Free; D014451:Ubiquinone; D013108:Sphingomyelin Phosphodiesterase; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases