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.
Ogino
Tetsuya
T
Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama 700-8558, Japan. togino@md.okayama-u.ac.jp
Ozaki
Michitaka
M
Hosako
Mutsumi
M
Omori
Masako
M
Okada
Shigeru
S
Matsukawa
Akihiro
A
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002700:Chloramines / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019169:Jurkat Cells; D018384:Oxidative Stress; D010766:Phosphorylation
D002700:Chloramines; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; C030816:chloramine; D002118:Calcium