Activation of c-Jun N-terminal kinase is essential for oxidative stress-induced Jurkat cell apoptosis by monochloramine.

Leukemic cell apoptosis may be enhanced by appropriate oxidative stress. We report here the mechanism of Jurkat cell apoptosis by monochloramine (NH(2)Cl), a neutrophil-derived oxidant. NH(2)Cl induced caspase-dependent apoptosis, which was preceded by cytochrome c and Smac/Diablo release from mitochondria. Within 10min of NH(2)Cl treatment, c-Jun N-terminal kinase (JNK) activation and elevation of cytosolic Ca(2+) were observed. JNK inhibitors (SP600125 or JNK inhibitor VIII) significantly suppressed the apoptosis as well as caspase cleavage and cytochrome c release. In contrast, Ca(2+) chelation by EGTA+acetoxymethyl-EGTA had no effects on apoptosis. Our results indicated that JNK activation contributed most importantly to the NH(2)Cl-induced apoptosis.