title: Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells.
abstract: The mechanisms underlying effects of aging on functions of pro-angiogenic endothelial progenitor cells (EPCs) are poorly understood. Previous studies demonstrated that human EPCs express high levels of antioxidant enzymes as compared to mature endothelial cells. Here, we hypothesized that aging impairs antioxidant capacity of EPCs. So called "early EPCs" derived from cultured blood mononuclear cells were obtained from healthy young (average=24 years old) and old (average=72 years old) subjects. In EPCs of old subjects, the levels of glutathione peroxidase-1 (GPX1) protein and enzymatic activity were significantly reduced. The serum selenium levels in young and old subjects were not significantly different. Increasing selenium concentration in the cell culture also did not affect the protein levels of GPX1, suggesting the reduced GPX1 in old subject's EPCs is selenium independent. Expressions of catalase, Mn-superoxide dismutase (MnSOD), and CuZnSOD were not affected by aging. EPCs of old subjects were more sensitive to oxidative stress induced by H(2)O(2) as compared with EPCs of young subjects, suggesting that impairment of GPX1 during aging may contribute to low survival ability of EPCs in response to oxidative stress. The results indicate that GPX1 may represent a potential therapeutic target for enhancement of regenerative capacity of EPCs in old subjects.
authors.affiliation: Department of Anesthesiology and Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. he.tongrong@mayo.edu
authors.forename: Tongrong
authors.initials: T
authors.lastname: He
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
authors.forename: Zvonimir S
authors.initials: ZS
authors.lastname: Katusic
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases; D018036:Selenium Compounds / Q000097:blood / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D055815:Young Adult; D000094765:Glutathione Peroxidase GPX1
chemical_list: D018036:Selenium Compounds; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human