Upregulation and phosphorylation of HspB1/Hsp25 and HspB5/αB-crystallin after transient middle cerebral artery occlusion in rats
Upregulation and phosphorylation of HspB1/Hsp25 and HspB5/αB-crystallin after transient middle cerebral artery occlusion in rats
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DOI：
10.1007/s12192-017-0794-9
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发表时间：
2017-07-01
影响因子：
3.8
通讯作者：
Golenhofen, Nikola
中科院分区：
文献类型：
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作者：
Bartelt-Kirbach, Britta;Slowik, Alexander;Golenhofen, Nikola
缺血性中风导致细胞功能障碍、细胞死亡和毁灭性的临床结果。脑细胞通过应激反应对这种细胞应激作出反应，其中热休克蛋白的上调导致内源性神经保护能力的激活。小热休克蛋白（HspB）家族的几个成员已被证明具有神经保护作用。然而，尚未有系统的研究，检查所有的热休克蛋白在脑缺血。在这里，我们进行了一项全面的比较研究，包括中风动物模型中的所有HspB，即，短暂性大脑中动脉闭塞1小时，随后再灌注23小时。在mRNA水平上，研究的11种HspBs中，HspB 1/Hsp 25、HspB 3、HspB 4/α A-晶体蛋白、HspB 5/α B-晶体蛋白、HspB 7/cvHsp和HspB 8/Hsp 22在梗死半球大脑皮层的梗死周围区域中显著上调。HspB 1和HspB 5达到最高的mRNA水平，并且在蛋白水平上也上调，这表明这些HspB可能在功能上最相关。有趣的是，在梗死皮质，HspB 1和HspB 5主要分配给神经元和神经胶质细胞在较小程度上。此外，发现这两种蛋白质在缺血时被磷酸化。我们的数据表明，在所有的热休克蛋白B，热休克蛋白B1和热休克蛋白B5可能是最重要的神经元的应激反应，缺血/再灌注损伤的脑，可能参与神经保护。
Ischemic stroke leads to cellular dysfunction, cell death, and devastating clinical outcomes. The cells of the brain react to such a cellular stress by a stress response with an upregulation of heat shock proteins resulting in activation of endogenous neuroprotective capacities. Several members of the family of small heat shock proteins (HspBs) have been shown to be neuroprotective. However, yet no systematic study examined all HspBs during cerebral ischemia. Here, we performed a comprehensive comparative study comprising all HspBs in an animal model of stroke, i.e., 1 h transient middle cerebral artery occlusion followed by 23 h of reperfusion. On the mRNA level out of the 11 HspBs investigated, HspB1/Hsp25, HspB3, HspB4/alpha A-crystallin, HspB5/alpha B-crystallin, HspB7/cvHsp, and HspB8/Hsp22 were significantly upregulated in the peri-infarct region of the cerebral cortex of infarcted hemispheres. HspB1 and HspB5 reached the highest mRNA levels and were also upregulated at the protein level, suggesting that these HspBs might be functionally most relevant. Interestingly, in the infarcted cortex, both HspB1 and HspB5 were mainly allocated to neurons and to a lesser extent to glial cells. Additionally, both proteins were found to be phosphorylated in response to ischemia. Our data suggest that among all HspBs, HspB1 and HspB5 might be most important in the neuronal stress response to ischemia/reperfusion injury in the brain and might be involved in neuroprotection.