PCMT1 Ameliorates Neuronal Apoptosis by Inhibiting the Activation of MST1 after Subarachnoid Hemorrhage in Rats

Mammalian sterile 20-like kinase 1 (MST1) is found to promote neuronal apoptosis. Protein- l -isoaspartate ( d -aspartate) O -methyltransferase (PCMT1), an anti-apoptosis factor, was recently identified as an MST1-interacting protein. This study aims to explore the potential role of PCMT1 in reducin...

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Published in:Translational stroke research 2017-10, Vol.8 (5), p.474-483
Main Authors: Shi, Ligen, Al-Baadani, Ammar, Zhou, Keren, Shao, Anwen, Xu, Shenbin, Chen, Sheng, Zhang, Jianmin
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Biomedical and Life Sciences
Biomedicine
Biotechnology
Cardiology
Carotid arteries
Experiments
Kinases
Laboratory animals
Neurology
Neurosciences
Neurosurgery
Original Article
Proteins
Traumatic brain injury
Vascular Surgery
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Summary:Mammalian sterile 20-like kinase 1 (MST1) is found to promote neuronal apoptosis. Protein- l -isoaspartate ( d -aspartate) O -methyltransferase (PCMT1), an anti-apoptosis factor, was recently identified as an MST1-interacting protein. This study aims to explore the potential role of PCMT1 in reducing MST1-induced neuronal apoptosis after subarachnoid hemorrhage (SAH) in rats. One hundred ninety-eight male Sprague-Dawley rats were used. An exogenous PCMT1 agonist, CGP 3466B, was injected subcutaneously 1 h after the SAH induced by endovascular perforation. Chelerythrine or calyculin A was given immediately via intracerebroventricular administration after SAH. The SAH grade, Garcia score, and brain water content were measured at 24 and 72 h after the SAH. Neuronal apoptosis was detected by an immunofluorescent assay. The expression levels of endogenous PCMT1, MST1, phospho-MST1 (p-MST1), cleaved MST1 (cl-MST1), and apoptosis-related proteins were studied by western blotting. The expression of PCMT1 and MST1 decreased, while the level of active caspase 3 increased in rats after SAH. CGP 3466B treatment improved neurobehavioral function, reduced brain water content, inhibited the activity of MST1, and relieved neuronal apoptosis. These neuroprotective effects were significantly weakened either through accelerating MST1 phosphorylation by calyculin A or increasing cl-MST1 by chelerythrine. PCMT1 inhibited neuronal apoptosis by reducing MST1 phosphorylation and the level of cl-MST1. PCMT1/MST1 pathway might be an alternative therapeutic target for alleviating early brain injury after SAH.
ISSN:1868-4483
1868-601X
DOI:10.1007/s12975-017-0540-8