Tumor necrosis factor-α and phorbol 12-myristate 13-acetate differentially modulate cytotoxic effect of nitric oxide generated by serum deprivation in neuronal PC12 cells

Kwang Chul Chung, Jae Hyun Park, Chul Hoon Kim, Young Soo Ahn

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Nitric oxide (NO) is a signaling molecule that mediates several physiological processes in a range of cell and tissue types. Here we investigated the effect of serum deprivation in the absence or presence of phorbol 12-myristate 13-acetate (PMA) or tumor necrosis factor-α (TNFα) on cell viability, NO formation, inducible NO synthase (iNOS) induction, and activation of mitogen-activated protein kinase in neuronal PC12 cells. Within 24 h of serum deprivation, apoptosis occurred in up to 65-70% of the cells, and significant levels of NO were generated. When PMA was added in serum- free medium, NO formation and cell death were decreased. In contrast, addition of TNFα in serum-free medium increased the levels of NO formation and apoptosis compared with those in serum-deprived cells. We have demonstrated that differential generation of NO levels by PMA or TNFα under conditions of serum deprivation is mediated by the same pattern of iNOS induction. NO formation via iNOS induction resulted in the activation of c- Jun N-terminal kinase (JNK) but not extracellular signal-regulated kinase. From this study it is suggested that the differential formation of cytotoxic NO by serum deprivation plus PMA or TNFα is primarily mediated by the induction of iNOS enzymes in neuronal PC12 cells and that its action is mediated by the activation of JNK.

Original languageEnglish
Pages (from-to)1482-1488
Number of pages7
JournalJournal of Neurochemistry
Volume72
Issue number4
DOIs
Publication statusPublished - 1999 Mar 31

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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