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OCT4B-190 protects against ischemic stroke by modulating GSK-3β/HDAC6
- Source :
- Experimental Neurology. 316:52-62
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- 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-3β (GSK-3β) 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-3β 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-3β 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-3β activity and HDAC6 expression. In addition, we found that GSK-3β and HDAC6 were co-expressed in the cytoplasm of neurons, and OCT4B-190 had an effect on interactions between GSK-3β 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-3β and HDAC6 simultaneously, which may be an attractive therapeutic strategy for ischemic stroke.
- Subjects :
- Male
0301 basic medicine
Cytoplasm
Programmed cell death
Regulator
Striatum
Biology
Histone Deacetylase 6
Neuroprotection
Brain Ischemia
Mice
03 medical and health sciences
0302 clinical medicine
Developmental Neuroscience
Cellular stress response
medicine
Animals
Hypoxia, Brain
Glycogen synthase
Stroke
Cells, Cultured
Cerebral Cortex
Neurons
Glycogen Synthase Kinase 3 beta
Infarction, Middle Cerebral Artery
HDAC6
medicine.disease
Cell biology
Mice, Inbred C57BL
Neostriatum
030104 developmental biology
Neurology
biology.protein
Nervous System Diseases
Octamer Transcription Factor-3
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00144886
- Volume :
- 316
- Database :
- OpenAIRE
- Journal :
- Experimental Neurology
- Accession number :
- edsair.doi.dedup.....9e3656694bc2e62f5ad6e3772593a289