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CIIA negatively regulates neuronal cell death induced by oxygen–glucose deprivation and reoxygenation

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Abstract

Brain ischemia causes neuronal injury leading to stroke and other related brain diseases. However, the precise mechanism of the ischemia-induced neuronal death remains unclear yet. In this study, we showed that CIIA suppressed neuronal cell death induced by oxygen and glucose deprivation followed by reoxygenation (OGD/R), which mimics ischemia and reperfusion in vivo, in neuroblastoma cell lines as well as primary cortical neurons. Furthermore, CIIA inhibited the OGD/R-induced stimulation of apoptosis signal-regulating kinase 1 (ASK1) and its downstream kinases including c-Jun amino-terminal kinase and p38 kinase, concomitantly blocking ASK1 homo-oligomerization and the binding between ASK1 and TRAF2. CIIA also repressed the OGD/R-induced activation of caspase-3 in neuronal cells. Taken together, our results suggest that CIIA attenuates neurotoxicity caused by OGD/R through inhibiting ASK1-dependent signaling events.

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Acknowledgments

We thank Drs. H. Ichijo for ASK1 cDNA, J. Han for MKK6 cDNA. This work was supported by the National Research Foundation Grant (2006-0093855) and a NRF Grant (2011-0030141) through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (MEST) of the Korea, and by a Korea University Grant (E.-J.C.).

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Authors and Affiliations

  1. Lab of Cell Death & Human Diseases, Department of Life Sciences, School of Life Sciences and Biotechnology, Korea University, Seoul, 136-701, Korea

    Sang Gil Hwang & Eui-Ju Choi

  2. Department of Molecular Biology, Sejong University, Seoul, 143-747, Korea

    Jaekyung Shim

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  1. Sang Gil Hwang
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Correspondence to Eui-Ju Choi.

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Hwang, S.G., Shim, J. & Choi, EJ. CIIA negatively regulates neuronal cell death induced by oxygen–glucose deprivation and reoxygenation. Mol Cell Biochem 397, 139–146 (2014). https://doi.org/10.1007/s11010-014-2181-5

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  • DOI: https://doi.org/10.1007/s11010-014-2181-5

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