Lipid peroxidation associated cardiolipin loss and membrane depolarization in rat brain mitochondria.
Oxidative stress induced by Fe2+ (50 microM) and ascorbate (2 mM) in isolated rat brain mitochondria incubated in vitro leads to an enhanced lipid peroxidation, cardiolipin loss and an increased formation of protein carbonyls. These changes are associated with a loss of mitochondrial membrane potential (depolarization) and an impaired activity of electron transport chain (ETC) as measured by MTT reduction assay. Butylated hydroxytoluene (0.2 mM), an inhibitor of lipid peroxidation, can prevent significantly the loss of cardiolipin, the increased protein carbonyl formation and the decrease in mitochondrial membrane potential induced by Fe2+ and ascorbate, implying that the changes are secondary to membrane lipid peroxidation. However, iron-ascorbate induced impairment of mitochondrial ETC activity is apparently independent of lipid peroxidation process. The structural and functional derangement of mitochondria induced by oxidative stress as reported here may have implications in neuronal damage associated with brain aging and neurodegenerative disorders.
Sen
Tanusree
T
Department of Biochemistry, Dr. B.C. Roy Post-graduate Institute of Basic Medical Sciences & IPGMER, Calcutta, India.
Sen
Nilkantha
N
Tripathi
Gayatri
G
Chatterjee
Uttara
U
Chakrabarti
Sasanka
S
D000375:Aging / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D002308:Cardiolipins / Q000378:metabolism*; D045222:Electron Transport Chain Complex Proteins / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats
D000975:Antioxidants; D002308:Cardiolipins; D045222:Electron Transport Chain Complex Proteins; D002084:Butylated Hydroxytoluene; D007501:Iron; D001205:Ascorbic Acid