Regulation of Bcl-2 protein expression during oxidative stress in neuronal and in endothelial cells.
The relationship between oxidative stress and Bcl-2 expression was investigated in two different experimental models of oxidative stress. Acute oxidative stress was assessed by measuring, with fluorescence microscopy and cytofluorimetry, the increase in fluorescence of the oxidation-sensitive probe dihydrorhodamine 123, both in retinal rod receptor cells exposed to bright light (0.32 mW/cm(2) for 15 minutes) and in human endothelial cells treated with the immunosuppressant cyclosporin A (200 microM for 21 h). In both cell types, acute oxidative stress reduced Bcl-2 expression and also caused a significant increase in the level of nucleosomes. Interestingly, chronic treatment with clinical concentrations of cyclosporin A (0.5-2.5 microM for 8 days) led to a significant increase in Bcl-2 expression, while nucleosomes were similar to control level. This suggests that up-regulation of Bcl-2 protein by low levels of oxidants may represent a critical factor in cellular adaptation to drug toxicity.
Divisione di Chirurgia Generale, Università di Pisa, Pisa, 56100, Italy. biancam@dfb.unipi.it
B
B
Longoni
E
E
Boschi
G C
GC
Demontis
P L
PL
Marchiafava
F
F
Mosca
D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015854:Up-Regulation
D019253:Proto-Oncogene Proteins c-bcl-2; D017392:Thiobarbituric Acid Reactive Substances