Oxidative stress signalling in the apoptosis of Jurkat T-lymphocytes.
The pathways of transduction of oxidative stress signals have been studied using the Jurkat T cell model. The oxidative stress was induced by exposure of the cells to 100 microM H(2)O(2). DNA damage was detected within 15 min after commencement of treatment. DNA damage repair occurred within about 1 h in cells exposed to oxidative stress for 15 min. In continuous exposure to stress, DNA repair was slower and control levels of DNA integrity were not reached. DNA repair did not involve gene transcription. H(2)O(2) at 100 microM caused cell death by necrosis as well as by apoptosis. Both these processes were induced by 15 min exposure to the stress stimulus. However, some important differences were found between necrosis and apoptosis. Necrosis was more rapid, began within an hour of treatment and continued to increase during the full duration of the experiment. But apoptosis was seen after 4 h from treatment and was conspicuous between 6 and 20 h after the start of treatment. The necrotic phase preceded apoptosis, although these did show an overlap. In the necrotic phase, Bcl-2, Caspase 8 genes were down regulated. The 6-20 h phase characterised by a marked increase in apoptosis is accompanied by the up regulation of both Bcl-2 and Caspase genes. Expression of the Fas and p53 genes was not altered in either phase. We also analysed the levels of expression of the scavenging genes whose gene products are involved in detoxification. No modulation of the antioxidant enzymes, catalase, Cu/Zn superoxide dismutase and glutathione peroxidase was detectable.
Chiaramonte
R
R
Department of Biomedical Sciences and Technologies, University of Milano, LITA-via Fratelli Cervi 93- 20090 Segrate (MI), Italy. raffaella.chiaramonte@unimi.it
Bartolini
E
E
Riso
P
P
Calzavara
E
E
Erba
D
D
Testolin
G
G
Comi
P
P
Sherbet
G V
GV
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019169:Jurkat Cells; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide