Affiliation:
1. Department of Cardiology The First Affiliated Hospital of Nanchang University Nanchang People's Republic of China
2. Department of Pharmacy The First Affiliated Hospital of Nanchang University Nanchang China
Abstract
AbstractMyocardial ischemia/reperfusion injury (MIRI) is a prevalent condition associated with numerous critical clinical conditions. miR‐322 has been implicated in MIRI through poorly understood mechanisms. Our preliminary analysis indicated potential interaction of CREB‐binding protein (CBP), a transcriptional coactivator and acetyltransferase, with HIF‐1α/β‐catenin, which might regulate miR‐322 expression. We, therefore, hypothesized that CBP/HIF‐1α/β‐catenin/miR‐322 axis might play a role in MIRI. Rat cardiomyocytes subjected to oxygen‐glucose deprivation /reperfusion (OGD/R) and Langendorff perfused heart model were used to model MIRI in vitro and in vivo, respectively. We used various techniques such as CCK‐8 assay, transferase dUTP nick end labeling staining, western blotting, RT‐qPCR, chromatin immunoprecipitation (ChIP), dual‐luciferase assay, co‐immunoprecipitation (Co‐IP), hematoxylin and eosin staining, and TTC staining to assess cell viability, apoptosis, and the levels of CBP, HIF‐1α, β‐catenin, miR‐322, and acetylation. Our results indicate that OGD/R in cardiomyocytes decreased CBP/HIF‐1α/β‐catenin/miR‐322 expression, increased cell apoptosis and cytokines, and reduced cell viability. However, overexpression of CBP or miR‐322 suppressed OGD/R‐induced cell injury, while knockdown of HIF‐1α/β‐catenin further exacerbated the damage. HIF‐1α/β‐catenin bound to miR‐322 promoter to promote its expression, while CBP acetylated HIF‐1α/β‐catenin for stabilization. Overexpression of CBP attenuated MIRI in rats by acetylating HIF‐1α/β‐catenin to stabilize their expression, resulting in stronger binding of HIF‐1α/β‐catenin with the miR‐322 promoter and subsequent increased miR‐322 levels. Therefore, activating CBP/HIF‐1α/β‐catenin/miR‐322 signaling may be a potential approach to treat MIRI.
Funder
National Natural Science Foundation of China
Subject
Genetics,Molecular Biology,Biochemistry,Biotechnology
Cited by
1 articles.
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