Authors: Mockett RJ; Orr WC; Rahmandar JJ; Benes JJ; Radyuk SN; Klichko VI; Sohal RS
Abstract: The general objective of this study was to examine the role of mitochondria in the aging process. Two alternative hypotheses were tested: (i) that overexpression of Mn superoxide dismutase (Mn SOD) in the mitochondria of Drosophila melanogaster would slow the accrual of oxidative damage and prolong survival or (ii) that there is an evolved optimum level of superoxide anion radical, such that overexpression of Mn SOD would have deleterious or neutral effects. Microinjection and mobilization of a transgene, which contained a 9-kb genomic sequence encoding Mn SOD, produced 15 experimental lines overexpressing Mn SOD by 5-116% relative to the parental y w strain. Comparisons between these lines and control lines containing inserted vector sequences alone indicated that the mean longevity of the experimental lines was decreased by 4-5% relative to controls. There were no compensatory changes in the metabolic rate, level of physical activity, or the levels of other antioxidants, namely Cu-Zn SOD, catalase, and glutathione. There were no differences between groups in rates of mitochondrial hydrogen peroxide release, protein oxidative damage, or resistance to 100% oxygen or starvation conditions. The experimental lines had a marginally increased resistance to moderate heat stress. These results are consistent with the existence of an optimum level of Mn SOD activity which minimizes oxidative stress. The naturally evolved level of Mn SOD activity in Drosophila appears to be near the optimum required under normal conditions, although the optimum may be shifted to a higher level under more stressful conditions.Keywords: Aging/*physiology; Animals; Animals, Genetically Modified; Drosophila melanogaster/physiology; Hot Temperature; Longevity/physiology; Mitochondria/*enzymology; Models, Biological; Oxidative Stress/physiology; Recombinant Proteins/metabolism; Starvation/metabolism; Superoxide Dismutase/genetics/*metabolism
Journal: Archives of biochemistry and biophysics
Date: Nov. 5, 1999
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Mockett RJ, Orr WC, Rahmandar JJ, Benes JJ, Radyuk SN, Klichko VI, Sohal RS (1999) Overexpression of Mn-containing superoxide dismutase in transgenic Drosophila melanogaster. Archives of biochemistry and biophysics 371: 260-9.