Oxidative stress-related alteration of the copy number of mitochondrial DNA in human leukocytes.
The role of oxidative stress in the regulation of the copy number of mitochondrial DNA (mtDNA) in human leukocytes is unclear. In this study, we investigated the redox factors in plasma that may contribute to the alteration of mtDNA copy number in human leukocytes. A total of 156 healthy subjects of 25-80 years of age who exhibited no significant difference in the distribution of subpopulations of leukocytes in blood were recruited. Small-molecular-weight antioxidants and thiobarbituric acid reactive substances (TBARS) in plasma and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 4,977bp deletion of mtDNA in leukocytes were determined. The mtDNA copy number in leukocytes was determined by real-time PCR. The results showed that the copy number of mtDNA in leukocytes was changed with age in a biphasic manner that fits in a positively quadratic regression model (P = 0.001). Retinol (P = 0.005), non-protein thiols (P = 0.001) and ferritin (P = 0.004) in plasma and total glutathione in erythrocytes (P = 0.046) were the significant redox factors that correlated with the mtDNA copy number in leukocytes in a positive manner. By contrast, alpha-tocopherol levels in plasma (P = 0.001) and erythrocytes (P = 0.033) were negatively correlated with the mtDNA copy number in leukocytes. Three oxidative indices including the incidence of 4,977 bp deletion of mtDNA (P = 0.016) and 8-OHdG content in leukocytes (P = 0.003) and TBARS in plasma (P = 0.001) were all positively correlated with the copy number of mtDNA in leukocytes. Taken these findings together, we suggest that the copy number of mtDNA in leukocytes is affected by oxidative stress in blood circulation elicited by the alteration of plasma antioxidants/prooxidants and oxidative damage to DNA.
Liu
Chin-San
CS
Department of Neurology and Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
Tsai
Ching-Shan
CS
Kuo
Chen-Ling
CL
Chen
Haw-Wen
HW
Lii
Chong-Kuei
CK
Ma
Yi-Shing
YS
Wei
Yau-Huei
YH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000097:blood; D018628:Gene Dosage; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013438:Sulfhydryl Compounds / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014801:Vitamin A / Q000097:blood
D000975:Antioxidants; D004272:DNA, Mitochondrial; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D006710:Homocysteine; D014801:Vitamin A; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005293:Ferritins; D003849:Deoxyguanosine; D005978:Glutathione