Selective protection by hsp 70 against cytotoxic drug-, but not Fas-induced T-cell apoptosis

The phenomenon of heat-shock (HS) protection to many cytotoxic insults has previously been described; however: the specific molecular mechanism underl ying this MS-mediated protection remains undefined. To gain insight into th is protective mechanism, heat-shocked Jurkat T cells were treated with a ra nge of cytotoxic agents. Those against which HS conferred protection (campt othecin and actinomycin D) were compared with agents against which HS showe d no protective effect (anti-Fas monoclonal antibody (mAb)). Reactive oxyge n species (ROS) production was found to be an event common to apoptosis ind uced by camptothecin and actinomycin D, whereas Fas-mediated apoptosis was shown to occur via a ROS-independent mechanism. The selective protection ob served against these agents was found to be mimicked by pretreatment with a ntioxidant compounds. Furthermore, this antioxidant protection appears to b e occurring downstream of ROS production. Experiments were extended using h eat-shock protein (hsp) 70 gene-transfected Jurkat T cells to confirm that the protective effects observed were caused by hsp 70 synthesis rather than any other cellular response to HS. Bcl-2 expression levels were also exami ned to determine whether any correlation existed between Bcl-2- and hsp 70- mediated protection.