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Involvement of p38 Mitogen-Activated Protein Kinase and Apoptosis Signal-Regulating Kinase-1 in Nitric Oxide-Induced Cell Death in PC12 Cells

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Abstract

Although nitric oxide (NO) plays key signaling roles in the nervous systems, excess NO leads to cell death. In this study, the involvement of p38 mitogen-activated protein kinase (p38 MAPK) and apoptosis signal-regulating kinase-1 (ASK1) in NO-induced cell death was investigated in PC12 cells. NO donor transiently activated p38 MAPK in the wild type parental PC12 cells, whereas the p38 MAPK activation was abolished in NO-resistant PC12 cells (PC12-NO-R). p38 MAPK inhibitors protected the cells against NO-induced death, whereas the inhibitors were not significantly protective against the cytotoxicity of reactive oxygen species. Stable transfection with dominant negative p38 MAPK mutant reduced NO-induced cell death. Stable transfection with dominant negative mutant of ASK1 attenuated NO-stimulated activation of p38 MAPK and decreased NO-induced cell death. These results suggest that p38 MAPK and its upstream regulator ASK1 are involved in NO-induced PC12 cell death.

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  1. Department of Biochemistry, College of Medicine, Chung-Ang University, Seoul, Korea

    Ok-Jin Han, Keun Ho Joe, Seong Won Kim, Hee Sung Lee, Nyoun Soo Kwon, Kwang Jin Baek & Hye-Young Yun

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  1. Ok-Jin Han
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Han, OJ., Joe, K.H., Kim, S.W. et al. Involvement of p38 Mitogen-Activated Protein Kinase and Apoptosis Signal-Regulating Kinase-1 in Nitric Oxide-Induced Cell Death in PC12 Cells. Neurochem Res 26, 525–532 (2001). https://doi.org/10.1023/A:1010917129951

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