The Protective Effects of Inosine Against Chemical Hypoxia on Cultured Rat Oligodendrocytes
The Protective Effects of Inosine Against Chemical Hypoxia on Cultured Rat Oligodendrocytes
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DOI：
10.1007/s10571-011-9719-9
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发表时间：
2011-06
影响因子：
4
通讯作者：
Q. Ma;Hao Yang;Xianghui Zhao;Yu-kai Zhang;An-hui Yao;Peng Cheng;Ya-Bin Xie;Haibo Zhao;G. Ju;F. Kuang
中科院分区：
文献类型：
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作者：
Q. Ma;Hao Yang;Xianghui Zhao;Yu-kai Zhang;An-hui Yao;Peng Cheng;Ya-Bin Xie;Haibo Zhao;G. Ju;F. Kuang
肌苷是一种嘌呤核苷，被认为是保护神经细胞，包括神经元和星形胶质细胞免受缺氧损伤。然而，是否少突胶质细胞（OLs）也可以保护缺氧肌苷是未知的。本研究采用ATP法、MTT法、PI-Hoechst染色、TUNEL法和免疫细胞化学等方法，研究肌苷对鱼藤酮介导的化学性缺氧损伤原代培养大鼠OLs的影响，并探讨其作用机制。结果表明，鱼藤酮暴露24小时造成细胞死亡和受损的活力在未成熟和成熟的OL，而预处理的10 mM肌苷30分钟前鱼藤酮管理显着减少细胞死亡，提高OL的活力。鱼藤酮暴露后120分钟给予相同浓度的肌苷也提高了受损成熟OL的活力。硝基酪氨酸免疫细胞化学和细胞内ATP含量的测定表明，肌苷可能通过为细胞提供ATP和清除过氧亚硝基阴离子而保护OLs。此外，未成熟的OLs比成熟的OLs更容易受到缺氧的影响;在相同的损伤程度下，肌苷对未成熟和成熟的OLs的保护作用不同。实时荧光定量PCR显示，腺苷受体的表达在这两个阶段的OLs之间是不同的。这些数据表明，肌苷作为抗氧化剂和ATP提供者保护OL免受缺氧损伤，并且肌苷对OL的保护作用随细胞分化而变化，可能是由于腺苷受体表达谱。由于OL在中枢神经系统中形成髓鞘，肌苷可用作治疗脱髓鞘相关疾病的有前途的药物。
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.