Effect of short-term caloric restriction on H2O2 production and oxidative DNA damage in rat liver mitochondria and location of the free radical source

被引:123
作者
Gredilla, R [1 ]
Barja, G [1 ]
López-Torres, M [1 ]
机构
[1] Univ Complutense Madrid, Fac Biol, Dept Anim Biol Anim Physiol 2, E-28040 Madrid, Spain
基金
新加坡国家研究基金会;
关键词
oxidative stress; oxygen radicals; free radical production;
D O I
10.1023/A:1010603206190
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
oxygen free radicals (ROS) of mitochondrial origin seem to be involved in aging. Whereas in other tissues complexes I or III of the respiratory chain contain the ROS generators, in this study we find that rat liver mitochondria generate oxygen radicals at complexes 1, II, and III. Short-term (6 weeks) caloric restriction significantly decreased H2O2 production in rat liver mitochondria. This decrease in ROS production was located at complex I because it occurred with complex I-linked substrates (pyruvate/malate), but did not reach statistical significance with the complex II-linked substrate succinate, The mechanism responsible for the lowered ROS production was not a decrease in oxygen consumption, Instead, the mitochondria of caloric-restricted animals released less ROS per unit electron flow. This was due to a decrease in the degree of reduction of the complex I generator. Furthermore, oxidative damage to mitochondrial and nuclear DNA was also decreased in the liver by short-term caloric restriction. The results agree with the idea that caloric restriction delays aging, at least in part, by decreasing the rate of mitochondrial ROS generation and thus the rate of attack to molecules, like DNA, highly relevant for the accumulation of age-dependent changes.
引用
收藏
页码:279 / 287
页数:9
相关论文
共 37 条
[1]   Localization at complex I and mechanism of the higher free radical production of brain nonsynaptic mitochondria in the short-lived rat than in the longevous pigeon [J].
Barja, G ;
Herrero, A .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1998, 30 (03) :235-243
[2]   Oxidative damage to mitochondrial DNA is inversely related to maximum life span in the heart and brain of mammals [J].
Barja, G ;
Herrero, A .
FASEB JOURNAL, 2000, 14 (02) :312-318
[3]   Mitochondrial free radical production and aging in mammals and birds [J].
Barja, G .
TOWARDS PROLONGATION OF THE HEALTHY LIFE SPAN: PRACTICAL APPROACHES TO INTERVENTION, 1998, 854 :224-238
[4]   Mitochondrial oxygen radical generation and leak: Sites of production in state 4 and 3, organ specificity, and relation to aging and longevity [J].
Barja, G .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1999, 31 (04) :347-366
[5]   LOW MITOCHONDRIAL FREE-RADICAL PRODUCTION PER UNIT O-2 CONSUMPTION CAN EXPLAIN THE SIMULTANEOUS PRESENCE OF HIGH LONGEVITY AND HIGH AEROBIC METABOLIC-RATE IN BIRDS [J].
BARJA, G ;
CADENAS, S ;
ROJAS, C ;
PEREZCAMPO, R ;
LOPEZTORRES, M .
FREE RADICAL RESEARCH, 1994, 21 (05) :317-327
[6]  
Barja G, 1999, METHODS AGING RES, P533
[7]  
Beckman K B, 1996, Methods Enzymol, V264, P442, DOI 10.1016/S0076-6879(96)64040-3
[8]   The free radical theory of aging matures [J].
Beckman, KB ;
Ames, BN .
PHYSIOLOGICAL REVIEWS, 1998, 78 (02) :547-581
[9]   MITOCHONDRIAL GENERATION OF HYDROGEN-PEROXIDE - GENERAL PROPERTIES AND EFFECT OF HYPERBARIC-OXYGEN [J].
BOVERIS, A ;
CHANCE, B .
BIOCHEMICAL JOURNAL, 1973, 134 (03) :707-716
[10]   ROLE OF UBIQUINONE IN MITOCHONDRIAL GENERATION OF HYDROGEN-PEROXIDE [J].
BOVERIS, A ;
CADENAS, E ;
STOPPANI, AOM .
BIOCHEMICAL JOURNAL, 1976, 156 (02) :435-444