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Regulation of c-Jun N-terminal kinase activation in hydrogen peroxide induced neurotoxicity

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Journal of Neurocytology

Abstract

C-Jun N-terminal kinase 1 and 2 (JNK1/2) have been shown to be transiently activated and involved in neurotoxicity. We searched for possible upstream molecules, which are responsible for the regulation of hydrogen peroxide-(H2O2) induced JNK1/2 activation and JNK1/2-mediated apoptotic-like cell death in cultured rat cortical neurons. The results showed that JNK1/2 activation (monitored by anti-diphosphorylated JNK1/2 antibody) was largely prevented by elimination of extracellular Ca2+ or blockage of NMDA-receptors (NMDA-R), and was weakly but significantly decreased by blockage of L-type voltage-gated calcium channel (L-VGCC); furthermore, JNK1/2 activation was largely prevented by inhibition of Ca2+/calmodulin-dependent protein kinase-II (CaMKII) and protein-tyrosine kinases (PTK). We also found that H2O2-induced apoptotic-like cell death was partially prevented by elimination of extracellular Ca2+, or by inhibition of NMDA-R, L-VGCC, PTK and CaMKII, respectively. The above results suggest that in H2O2-induced neurotoxicity, JNK1/2 activation is mainly mediated by NMDA-R and L-VGCC. Consequently, PTK and CaMKII are critical intermediaries in JNK1/2 activation and are mainly responsible for JNK1/2-mediated apoptotic-like cell death.

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Authors and Affiliations

  1. Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, Jinagsu, 221002, People's Republic of China

    Wei Wang, Xiao-Yu Hou, Can Gao, Yong Liu, Yan-Yan Zong & Guang-Yi Zhang

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  1. Wei Wang
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  2. Xiao-Yu Hou
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  4. Yong Liu
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Wang, W., Hou, XY., Gao, C. et al. Regulation of c-Jun N-terminal kinase activation in hydrogen peroxide induced neurotoxicity. J Neurocytol 32, 143–151 (2003). https://doi.org/10.1023/B:NEUR.0000005599.10952.33

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