Ginkgolide B Protects Neurons from Ischemic Injury by Inhibiting the Expression of RTP801
Ginkgolide B Protects Neurons from Ischemic Injury by Inhibiting the Expression of RTP801
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DOI：
10.1007/s10571-015-0189-3
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发表时间：
2015-10-01
影响因子：
4
通讯作者：
Zhu, Li
中科院分区：
文献类型：
--
作者：
Wu, Xiaomei;Su, Jianyou;Zhu, Li
RTP 801（也称为REDD 1）是一种应激相关蛋白，由几种环境应激如缺血和香烟烟雾诱导。虽然缺血可以显著上调RTP 801在脑缺血中的表达，但到目前为止，对RTP 801与缺血中神经元死亡的确切关系知之甚少。本研究以原代培养的皮质神经元为体外缺血模型，发现RTP 801的表达随着缺血时间的延长而进行性增加，其中RTP 801的表达与神经元中乳酸脱氢酶（LDH）的释放呈正相关，RTP 801的敲低促进了缺血再灌注神经元的存活。银杏内酯B（GB）可显著提高缺血再灌注后神经元细胞活力，减少LDH释放，同时降低缺血再灌注后神经元RTP 801 mRNA和蛋白水平。此外，通过应用磷脂酰肌醇3-激酶（PI 3 K）的特异性抑制剂LY 294002，GB诱导的RTP 801表达减少被阻断。以上结果表明，RTP 801对缺血神经元有损伤作用，GB可能通过PI 3 K途径抑制RTP 801的表达，从而保护神经元免受缺血损伤。
RTP801 (also known as REDD1), a stress-related protein, is induced by several environmental stresses such as ischemia and cigarette smoke. Although ischemia can dramatically up-regulate RTP801 expression in brain ischemia, up to now, the exact relation between RTP801 and neuronal death in ischemia is poorly understood. In the current study, using oxygen and glucose deprivation as an in vitro ischemic model in primary cultured cortical neurons, we found that the expression of RTP801 increased progressively with prolongation of ischemic duration, in which the expression of RTP801 is positively correlated with the release of lactate dehydrogenase (LDH) in neurons, and knockdown of RTP801 promoted neuronal survival in ischemia-reperfusion. It was further found that ginkgolide B (GB) could significantly increase cell viability and decrease LDH release, and at the same time reduce the levels of RTP801 mRNA and protein in neurons after ischemia and reperfusion. Moreover, GB-induced reduction in expression of RTP801 was blocked by application of LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K). These results demonstrate that RTP801 could play a detrimental role on neurons in ischemia, and GB might protect neurons against ischemic injury by inhibiting RTP801 expression via PI3K pathway.