JNK and p38 were involved in hypoxia and reoxygenation-induced apoptosis of cultured rat cerebellar granule neurons
JNK and p38 were involved in hypoxia and reoxygenation-induced apoptosis of cultured rat cerebellar granule neurons
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DOI：
10.1016/j.etp.2008.06.004
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发表时间：
2009-03-01
影响因子：
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通讯作者：
Yan, Guang-Mei
中科院分区：
文献类型：
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作者：
Liu, Al-Ling;Wang, Xin-Wei;Yan, Guang-Mei
作为中风中发现的再灌注损伤的模型，我们用缺氧接着复氧处理小脑颗粒神经元（CGNs）。缺氧3 h再复氧24 h（H/R）可诱导CGN典型的凋亡。暴露于H/R的CGN通过激活JNK，增加p38的表达，并最终导致CGN死亡。SB 203580和SP 600125预处理均能抑制H/R诱导的CGN凋亡，且SB 203580的抑制作用大于SP 600125。此外，我们还发现，H/R暂时激活Akt和失活糖原合成激酶-3 β（GSK-3 β），这两种蛋白的功能在细胞存活和能量代谢中很重要。这些结果表明，H/R通过增强JNK和p38活性诱导CGN凋亡，这至少部分地促进了H/R诱导的CGN凋亡。(C)2008年Elsevier GmbH。All rights reserved.
As a model of the reperfusion injury found in stroke, we treated cerebellar granule neurons (CGNs) with hypoxia followed by reoxygenation. Hypoxia for 3 h followed by 24 h reoxygenation (H/R) induced a typical apoptosis of CGNs. CGNs exposed to H/R responded by activating JNK, increasing the expression of p38 and ultimately caused CGNs dying. Furthermore, apoptosis of CGNs induced by H/R was inhibited by pre-treatment with SB203580 or SP600125, and the inhibitory effect of SB203580 was greater than that of SP600125. Additionally, we also found that H/R temporally activated Akt and inactivated glycogen synthesis kinase-3 beta (GSK-3 beta), two proteins the functions of which were important in cell survival and energy metabolism. These findings demonstrated that H/R-induced apoptosis in CGNs by enhancing JNK and p38 activity, which contributed at least in part to H/R-induced apoptosis of CGNs. (C) 2008 Elsevier GmbH. All rights reserved.