Molecular mechanism of environmental stress-induced apoptosis in fish

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The neutral sphingomyelinase １ (nSMase1) is involved in environmental stress-i duced apoptosis infish. To reveal the molecular mechanism, we examined the invo vement of the stress-activated protein kinase/c-jun N-terminal kinase (SAPK/JNK) system. Upon heat shock treatment, the protein kinase initiated a signal transduction pathway leading to cell death (apoptosis). Using recombinant JNK1 protein, we found that phosphorylation of nSMase1 occurred at serine-270. Treatment with heat shock rapidly enhanced the nSMase1-directed kinase activity of endogenous JNK. On the other hand, the mutant of JNK1 dominant negative was much less sensitve to heat shock. Our results strongly suggest that phosphorylation of nSMase1 in heat-shock-induced apoptosis is executed by JNK.