Abstract
We have previously reported that irradiated MOLT-4 cells developed a new protein p41 on 2-D PAGE dose and time dependently and that p41 was generated by the caspase-cleavage of p42/SETbeta, while sodium orthovanadate (vanadate) treatment inhibited the p41-induction. In the present study, we investigated mechanism(s) involved in the inhibition of radiation-induction of p41. Immunoblotting analysis and in vitro assays of caspases revealed that the inhibitory effect of vanadate was due to the suppression of caspase-activation. We further investigated the effect of vanadate on the course of caspase-activation and the apoptotic cell death of irradiated MOLT-4. As a result, we found that vanadate suppressed the cell death as well as the process related to the caspase-activation such as releases of cytochrome c and Smac/DIABLO from mitochondria, loss of mitochondrial membrane potential, and conformational change of Bax. These results indicated that vanadate acted on upstream event(s) of these releases, causing suppression of radiation-induced apoptotic cell death of MOLT-4. [J Radiat Res 44:448 (2003)]
