Orr W C, Arnold L A, Sohal R S
Department of Biological Sciences, Southern Methodist University, Dallas, TX 75275.
Mech Ageing Dev. 1992 May;63(3):287-96. doi: 10.1016/0047-6374(92)90006-y.
This study was conducted on Drosophila melanogaster mutants with different levels of catalase activity in order to assess the role of antioxidant defenses in the aging process. We present here the analysis of two mutant strains: the catn1/catn4 heterozygote which exhibits no detectable catalase activity and the catn2 homozygote which exhibits approximately 14% that of the parent reference strain. Since insects lack glutathione peroxidase activity, catalase activity provides the sole enzymatic mechanism for the removal of H2O2. Average and maximum life spans of flies were unaffected by the absence or low levels of catalase activity. The mutants however exhibited adaptive responses in their metabolic rate or glutathione content. The metabolic rate of flies was significantly lowered in the null mutants. Glutathione concentration tended to increase in flies with the hypomorphic catalase allele (exhibiting 14% of the normal catalase activity). Gamma-glutamylcysteine synthetase activity was significantly higher in the null flies. Activities of superoxide dismutase and glutathione reductase were unaffected. Results of this study indicate that 14% of the normal level of catalase activity allows flies to achieve both a normal life span and a normal metabolic potential. Small decreases in certain antioxidant defenses, frequently observed during aging, may be functionally not very consequential.
本研究以具有不同过氧化氢酶活性水平的黑腹果蝇突变体为对象,以评估抗氧化防御在衰老过程中的作用。我们在此展示对两种突变株的分析:catn1/catn4杂合子,其未表现出可检测到的过氧化氢酶活性;以及catn2纯合子,其过氧化氢酶活性约为亲本参照株的14%。由于昆虫缺乏谷胱甘肽过氧化物酶活性,过氧化氢酶活性是清除过氧化氢的唯一酶促机制。果蝇的平均寿命和最大寿命不受过氧化氢酶活性缺失或水平降低的影响。然而,这些突变体在代谢率或谷胱甘肽含量方面表现出适应性反应。无过氧化氢酶活性的突变体果蝇的代谢率显著降低。具有低表达过氧化氢酶等位基因(表现出正常过氧化氢酶活性的14%)的果蝇中,谷胱甘肽浓度趋于增加。无过氧化氢酶活性的果蝇中γ-谷氨酰半胱氨酸合成酶活性显著更高。超氧化物歧化酶和谷胱甘肽还原酶的活性未受影响。本研究结果表明,正常过氧化氢酶活性水平的14%能使果蝇实现正常寿命和正常代谢潜能。在衰老过程中经常观察到的某些抗氧化防御的小幅下降,在功能上可能影响不大。