Oxidative stress-induced apoptosis in dividing fibroblasts involves activation of p38 MAP kinase and over-expression of Bax: resistance of quiescent cells to oxidative stress.
Oxidative stress has been postulated to be involved in aging and age-related degenerative diseases. Cell death as a result of oxidative stress plays an important role in the age related diseases. Using human diploid fibroblasts (HDF) as model to study the mechanism of cell death induced by oxidative stress, a condition was standardized to induce apoptosis in the early passage sub-confluent HDFs by a brief exposure of cells to 250 microM hydrogen peroxide. It was observed that p38 MAP kinase (MAPK) was activated soon after the treatment followed by over-expression of Bax protein in cells undergoing apoptosis. An interesting finding of the present study is that the confluent, quiescent HDFs were resistant to cell death under identical condition of oxidative stress. The contact-inhibited quiescent HDFs exhibited increased glutathione level following H(2)O(2)-treatment, did not activate p38 MAP kinase, or over-express Bax, and were resistant to cell death. These findings indicated that there was a correlation between the cell cycle and sensitivity to oxidative stress. This is the first report to our knowledge that describes a relationship between the quiescence state and anti-oxidative defense. Furthermore, our results also suggest that the p38MAPK activation-Bax expression pathway might be involved in apoptosis induced by oxidative stress.
Naderi
J
J
Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset Ave, Windsor, ON N9B 3P4, Canada.
Hung
M
M
Pandey
S
S
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D020552:Comet Assay; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D048051:p38 Mitogen-Activated Protein Kinases
D000975:Antioxidants; C494826:BAX protein, human; D009097:Multienzyme Complexes; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D005978:Glutathione