Quantification of wild-type mitochondrial DNA and its 4.8-kb deletion in rat organs.
Oxidative damage to mitochondrial DNA (mtDNA) is considered a major contributor in aging. An age-dependent increase of oxidative damage and of the quantity of partially deleted mtDNA was reported for several rat and human organs. Here, a systematic investigation of ten different tissues and organs of 20-months-old rats was performed. The amount of mtDNA and age-dependent 4.8 kb deletion (delta mtDNA4834) was determined by competitive polymerase chain reaction, along with the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSHPx). The data were related to the corresponding metabolic rates. MtDNA content was highest in heart and lowest in spleen. delta mtDNA4834 was detected in all ten tissues and organs, and its amount was highest in liver and lowest in intestine. In heart, lung, muscle, and bone-marrow the deletion could not be quantified because of a point mutation, an A-->T transition at position 8107. Activities of SOD and GSHPx were highest in liver and lowest in intestinal mucosa. A negative correlation between mtDNA content and delta mtDNA4834, and a positive correlation between metabolic rate, GSHPx, and the deletion was found. These results suggest that the occurrence of delta mtDNA4834 in rat is related to oxidative stress.
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Laboratory of Biochemistry I, Swiss Federal Institute of Technology (ETH), Zürich.
Margue
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Richter
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D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D016133:Polymerase Chain Reaction; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000378:metabolism
D004272:DNA, Mitochondrial; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase