Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells

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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 H2O2 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.

Original languageEnglish (US)
Pages (from-to)447-452
Number of pages6
JournalMicrovascular Research
Volume78
Issue number3
DOIs
StatePublished - Dec 2009

Fingerprint

Endothelial cells
Aging of materials
Selenium
Oxidative stress
Oxidative Stress
Antioxidants
glutathione peroxidase GPX1
Endothelial Progenitor Cells
Catalase
Superoxide Dismutase
Cell culture
Glutathione
Cultured Cells
Blood Cells
Proteins
Endothelial Cells
Cell Culture Techniques
Blood
Survival

Keywords

  • Aging
  • Endothelial progenitor cells
  • GPX1
  • Human subjects
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Cardiology and Cardiovascular Medicine

Cite this

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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 H2O2 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.",
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AU - Katusic, Zvonimir S

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AB - 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 H2O2 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.

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