Selectivity of protein oxidative damage during aging in Drosophila melanogaster.
The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions.
Das
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Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90033, USA.
Levine
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Orr
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WC
Sohal
R S
RS
D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D000367:Age Factors; D000375:Aging; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D004331:Drosophila melanogaster; D004591:Electrophoresis, Polyacrylamide Gel; D005463:Fluoroacetates / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia; D015151:Immunoblotting; D008928:Mitochondria / Q000201:enzymology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D013696:Temperature
D005463:Fluoroacetates; D000154:Aconitate Hydratase; D010100:Oxygen