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 muM H2O2. DNA damage was detected within 15 min after commencement of treatment. DNA damage repair occurred within about 1 h in c ells exposed to oxidative stress for 15 min. In continuous exposure to stre ss, DNA repair was slower and control levels of DNA integrity were not reac hed. DNA repair did not involve gene transcription. H2O2 at 100 muM caused cell death by necrosis as well as by apoptosis. Both these processes were i nduced by 15 min exposure to the stress stimulus. However, some important d ifferences were found between necrosis and apoptosis. Necrosis was more rap id, 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 trea tment 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 Bc1-2 and Caspase genes. Expression of the Fas an d 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 det oxification. No modulation of the antioxidant enzymes, catalase, Cu/Zn supe roxide dismutase and glutatione peroxidase was detectable. (C) 2001 Wiley-L iss, Inc.