Correlation of mitochondrial superoxide dismutase and DNA polymerase beta in mammalian dermal fibroblasts with species maximal lifespan.
Eukaryotic cells have evolved elaborate mechanisms to preserve the fidelity of their genomic material in the face of chronic attack by reactive byproducts of aerobic metabolism. These mechanisms include antioxidant and DNA repair enzymes. Skin fibroblasts of long-lived mammalian species are more resistant to oxidative stress than those of shorter-lived species [Kapahi, P., Boulton, M.E., Kirkwood, T.B., 1999. Positive correlation between mammalian life span and cellular resistance to stress. Free Radic. Biol. Med. 26, 495-500], and we speculated that this is due to greater antioxidant and/or DNA repair capacities in longer-lived species. We tested this hypothesis using dermal fibroblasts from mammalian species with maximum lifespans between 5 and 122 years. The fibroblasts were cultured at either 18 or 3% O(2). Of the antioxidant enzymes only manganese superoxide dismutase was found to positively correlate with maximum lifespan (p<0.01). Oxidative damage to DNA is primary repaired by the base excision repair (BER) pathway. BER enzyme activities showed either no correlation (apurinic/apyrimidinic endonuclease), or correlated negatively (p<0.01) with donor species MLS (polymerase beta). Standard culture conditions (18% O(2)) induced both antioxidant and BER enzymes activities, suggesting that the 'normal' cell culture conditions widely employed are inappropriately hyperoxic, which likely confounds the interpretation of studies of cellular oxidative stress responses in culture.
Department of Biological Sciences, Brock University, St. Catharines, Ontario L2S 3A1, Canada.
Melanie F
MF
Brown
Jeffrey A
JA
Stuart
D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D019951:DNA Polymerase beta / Q000378:metabolism*; D020405:Dermis / Q000166:cytology / Q000201:enzymology*; D004285:Dogs; D005260:Female; D005347:Fibroblasts / Q000201:enzymology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006736:Horses; D006801:Humans; D008136:Longevity; D008252:Macaca fascicularis; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012756:Sheep; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019951:DNA Polymerase beta; D010100:Oxygen