In:
Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2020 ( 2020-01-07), p. 1-13
Abstract:
H19, a long noncoding RNA (lncRNA), reportedly protects myocardial cells (H9c2 cell line) against hypoxia-reoxygenation- (H/R-) induced injury. Dexmedetomidine (Dex) has an important myocardial protective effect, although its function and mechanism in cardiac ischemia/reperfusion (I/R) injury, especially for senile patients, requires further study. RNA N6-methyladenosine (m 6 A) is the most abundant endogenous RNA modification. However, the effect of Dex postconditioning on RNA m 6 A modification has rarely been reported. The aim of this study was to evaluate roles of H19 and m 6 A modification in Dex postconditioning of aged cardiomyocytes. Hydrogen peroxide (H 2 O 2 ) was used to induce senescence of H9c2 cells. After 6 h of hypoxia, H9c2 cells were exposed to different concentrations of dexmedetomidine (0, 500 nM, 1 μ M, and 2 μ M) for 6 h. After knockdown or overexpression of H19 and its downstream gene miR-29b-3p and cellular inhibitor of apoptosis protein 1 (cIAP1), Dex postconditioning experiments were performed to examine effects on myocardial cell injury. Global m 6 A levels after H/R with or without Dex postconditioning were measured with a colorimetric m 6 A RNA Methylation Quantification Kit. The mechanism by which RNA m 6 A methylation regulated genes mediating H19 expression was verified by m 6 A RNA immunoprecipitation (MeRIP), and the function of Dex postconditioning of aged cardiomyocytes was investigated. Dex postconditioning protected against H/R-induced injury of aged myocardial cells through H19/miR-29b-3p/cIAP1, increased methylation of RNA m 6 A elicited by H/R, and attenuated H/R-induced injury by suppressing expression of the RNA m 6 A demethylase gene alkB homolog 5 (ALKBH5). In addition, AKLBH5 regulated the expression of H19, and Dex postconditioning attenuated H/R-induced injury via ALKBH5 in aged cardiomyocytes.
Type of Medium:
Online Resource
ISSN:
1942-0900
,
1942-0994
DOI:
10.1155/2020/9250512
Language:
English
Publisher:
Hindawi Limited
Publication Date:
2020
detail.hit.zdb_id:
2455981-7
