Direct observation of release of cytochrome c from lipid-encapsulated protein by peroxide and superoxide: a possible mechanism for drug-induced apoptosis.
Release of cytochrome c from inside lipid vesicles and from inside proteoliposomes formed by cytochrome c oxidase has been studied by spectrophotometric methods. The protein encapsulated inside vesicles did not form complex with sodium azide solution added externally. Both hydrogen peroxide and superoxide were found to cause release of cytochrome c from the lipid encapsulated protein, which was detected from the distinct spectral changes due to the formation of the azide complex of cytochrome c in the solution. Cytochrome c encapsulated inside proteoliposomes containing cytochrome c oxidase (CcO) did not release the cytochrome c during enzymatic turnover of CcO. The anticancer drug, doxorubicin, was found to inhibit the biochemical function of cytochrome c oxidase and release of cytochrome c was observed from the proteoliposome encapsulating the protein during the enzymatic turnover in the presence of doxorubicin. The results indicated that the inhibition of enzymatic activity by doxorubicin possibly leads to the formation of reactive oxygen species, which induce the release of cytochrome c from inside to outside of the membrane.
Das
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N
Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Mambai, 400005, India.
Gupta
S
S
Mazumdar
S
S
D017209:Apoptosis; D003574:Cytochrome c Group / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D003576:Electron Transport Complex IV / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008081:Liposomes / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology*
D003574:Cytochrome c Group; D008081:Liposomes; D011510:Proteolipids; C020485:proteoliposomes; D013481:Superoxides; C039316:potassium superoxide; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D003576:Electron Transport Complex IV