Thousand and one kinase 1 protects MCAO-induced cerebral ischemic stroke in rats by decreasing apoptosis and pro-inflammatory factors.

ABSTRACT: BACKGROUND:Birth hypoxia causes neonatal mortality and morbidity. Hypoxia/ischemia can facilitate brain damage, causing various kinds of diseases, such as ischemic stroke. It is necessary to understand the potential underlying mechanisms of ischemic stroke. Previous studies revealed the involvement of thousand and one kinase 1 (TAOK1) in many cellular processes. METHODS:Herein, middle cerebral artery (MCA) occlusion (MCAO) was performed in rats to establish ischemic stroke in the animal model, and cortical neural stem cells from rats were treated with oxygen-glucose deprivation (OGD) to induce ischemic stroke cell model. The animal model of ischemic stroke was validated by Bederson and Zea-Longa neurological deficit scores and rotarod test. TAOK1 expression was examined by quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescent staining both in vivo and in vitro. RESULT:Compared with sham animals, the MCAO rats showed a significant increase in the neurological scores, and obvious motor behavioral deficits. Meanwhile, there was increased apoptosis and inflammatory response in the model group. TAOK1 overexpression reversed the OGD-induced cell injury, while TAOK1 knockdown exhibited the opposing effects. On the mechanism, the OGD-induced suppression of PI3K/AKT, and activation of mitogen-activated protein kinase (MAPK) signaling pathways were abolished by TAOK1 overexpression, and aggravated by TAOK1 knockdown in vitro. Moreover, we proved that the inhibitory effect of TAOK1 on OGD-induced apoptosis was dependent on the intracellular kinase activity. CONCLUSION:TAOK1 protected MCAO-induced cerebral ischemic stroke by decreasing the pro-inflammatory factors and apoptosis via PI3K/AKT and MAPK signaling pathways.

SUBMITTER: Li J 

PROVIDER: S-EPMC6822489 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature