OCT4B-190 protects against ischemic stroke by modulating GSK-3β/HDAC6
OCT4B-190 protects against ischemic stroke by modulating GSK-3β/HDAC6
复制标题
OCT4B-190 通过调节 GSK-3 beta/HDAC6 预防缺血性中风
DOI：
10.1016/j.expneurol.2019.04.005
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发表时间：
2019-06-01
影响因子：
5.3
通讯作者：
Xu, Yun
中科院分区：
文献类型：
--
作者：
Chen, Yanting;Wu, Zhengzheng;Xu, Yun
OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B and OCT4B1. The 190-amino-acid protein isoform (OCT4B-190) is one of the major products of OCT4B mRNA, the biological function of which is still not well defined. Recent evidence suggests that OCT4B-190 may function in the cellular stress response. The glycogen synthase kinase-3 beta (GSK-3 beta) and histone deacetylase 6 (HDAC6) are also key stress modulators that play critical roles in the ischemic cascades of stroke. Hence, we here further investigated the effects of OCT4B-190 in the experimental stroke, and explored the underlying roles of GSK-3 beta and HDAC6. We found that OCT4B-190 overexpression enhanced neuronal viability at 24 h after oxygen-glucose deprivation (OGD) treatment. Moreover, in male C57BL/6 mice subjected to transit middle cerebral artery occlusion (MCAO), OCT4B-190 overexpression reduced infarct volume and improved neurological function after stroke. Notably, we found spatio-temporal alterations of GSK-3 beta and HDAC6 in the ischemic cortex and striatum, which were affected by adenovirus-mediated OCT4B-190 overexpression. OCT4B-190 demonstrated similar impacts on neuronal cultures in vitro, downregulating OGD-induced GSK-3 beta activity and HDAC6 expression. In addition, we found that GSK-3 beta and HDAC6 were co-expressed in the cytoplasm of neurons, and OCT4B-190 had an effect on interactions between GSK-3 beta and HDAC6 in neuronal cultures subjected to OGD treatment. These findings suggest that OCT4B-190 exerts neuroprotection in the experimental stroke potentially by regulating actions of GSK-3 beta and HDAC6 simultaneously, which may be an attractive therapeutic strategy for ischemic stroke.
