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The Protective Effects of Inosine Against Chemical Hypoxia on Cultured Rat Oligodendrocytes

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Abstract

Inosine is a purine nucleoside and is considered protective to neural cells including neurons and astrocytes against hypoxic injury. However, whether oligodendrocytes (OLs) could also be protected from hypoxia by inosine is not known. Here we investigated the effects of inosine on primarily cultured rat OLs injured by rotenone-mediated chemical hypoxia, and the mechanisms of the effects using ATP assay, MTT assay, PI-Hoechst staining, TUNEL, and immunocytochemistry. Results showed that rotenone exposure for 24 h caused cell death and impaired viability in both immature and mature OLs, while pretreatment of 10 mM inosine 30 min before rotenone administration significantly reduced cell death and improved the viability of OLs. The same concentration of inosine given 120 min after rotenone exposure also improved viability of injured mature OLs. Immunocytochemistry for nitrotyrosine and cellular ATP content examination indicated that inosine may protect OLs by providing ATP and scavenging peroxynitrite for cells. In addition, immature OLs were more susceptible to hypoxia than mature OLs; and at the similar degree of injury, inosine protected immature and mature OLs differently. Quantitative real-time PCR revealed that expression of adenosine receptors was different between these two stages of OLs. These data suggest that inosine protect OLs from hypoxic injury as an antioxidant and ATP provider, and the protective effects of inosine on OLs vary with cell differentiation, possibly due to the adenosine receptors expression profile. As OLs form myelin in the central nervous system, inosine could be used as a promising drug to treat demyelination-involved disorders.

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Acknowledgments

The present study was supported by Grant 2009ZX09301-009-PT02, Grant 08Z028, and NSFC 30800325 in China.

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  1. Institute of Neurosciences, The Fourth Military Medical University, 17 West Changle Road, Xi’an, 710032, China

    Quan-Rui Ma, Hao Yang, Xiang-Hui Zhao, Yu-Kai Zhang, An-Hui Yao, Peng Cheng, Ya-Bin Xie, Hai-Kang Zhao, Gong Ju & Fang Kuang

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  1. Quan-Rui Ma
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  2. Hao Yang
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Correspondence to Gong Ju or Fang Kuang.

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Ma, QR., Yang, H., Zhao, XH. et al. The Protective Effects of Inosine Against Chemical Hypoxia on Cultured Rat Oligodendrocytes. Cell Mol Neurobiol 31, 1171–1186 (2011). https://doi.org/10.1007/s10571-011-9719-9

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