Affiliation:
1. Department of Neurology Shaanxi Provincial People's Hospital Xi'an China
Abstract
AbstractBackgroundBRCA1 associated protein (BRAP) participates in the regulation of myocardial infarction and atherosclerosis. But the function of BRAP in cerebral ischemia–reperfusion (CIR) injury has not been elucidated yet.MethodsBRAP expression in PC12 cells in response to oxygen–glucose deprivation/reoxygenation (OGD/R) treatment was examined with Western blot assay. PC12 cells underwent OGD/R‐treatment and were subsequently transfected with pcDNA‐BRAP or sh‐BRAP, followed by determination of viability, lactate dehydrogenase (LDH) production, apoptosis, inflammatory cytokine secretion, and oxidative stress marker protein levels. Paraoxonase 1 (PON1) promoter methylation was evaluated with methylation‐specific PCR assay. the effect of BRAP/PON1 axis on CIR injury was investigated by rescue experiments. Additionally, sh‐BRAP was injected into a middle cerebral artery occlusion (MCAO) rat model, and the changes of neurological damage were evaluated.ResultsBRAP overexpression exacerbated OGD/R‐induced viability reduction, LDH production, apoptosis, inflammatory cytokine secretion and oxidative stress in PC12 neuronal cells. In contrast, BRAP silencing showed the opposite results. Mechanistically, BRAP reduced PON1 expression by promoting DNA methyl transferase1 (DNMT1)‐mediated PON1 promoter methylation. PON1 silencing reversed BRAP‐mediated neuroprotection. Additionally, BRAP silencing alleviated CIR‐induced neurological damage in MCAO rats.ConclusionBRAP silencing suppressed OGD/R‐induced neuronal apoptosis, inflammation, and oxidative stress, and alleviated CIR‐induced neurological damage in MCAO rats through facilitating PON1 expression.
Subject
Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine
Cited by
1 articles.
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