Remote ischemic postconditioning alleviates myocardial ischemia/reperfusion injury by up-regulating ALDH2.
Eur Rev Med Pharmacol Sci
; 22(19): 6475-6484, 2018 10.
Article
em En
| MEDLINE
| ID: mdl-30338817
ABSTRACT
OBJECTIVE:
The myocardial ischemia/reperfusion (I/R) injury is a significant challenge, and the clinical significance of remote ischemic postconditioning (RIPostC) in cardioprotection has been confirmed. However, the molecular mechanism remains unclear. We aimed to explore the regulatory mechanism of RIPostC in myocardial I/R. MATERIALS ANDMETHODS:
A mouse model of myocardial I/R injury and cell model of oxygen-glucose deprivation (OGD)/re-oxygenation (OGD/R) injury were constructed. Infarct size was measured by Evans blue dye staining and TTC staining. mRNA and protein expression levels of aldehyde dehydrogenase 2 (ALDH2) were determined by RT-qPCR and Western blot analysis, respectively. Cell viability, p53 expression, apoptotic cells, expression of proteins related to apoptosis, and reactive oxygen species (ROS) generation were evaluated by CCK-8 assay, Western blot analysis, flow cytometry assay, Western blot analysis, and DCFH-DA staining, respectively. ALDH2 in H9c2 cells was knocked down, and its effects on cells treated with OGD/R and RIPostC were tested. How RIPostC affected ALDH2 expression was finally studied.RESULTS:
RIPostC reduced infarct size in mice and attenuated OGD/R-induced H9c2 cell injury. Myocardial I/R-induced down-regulation of ALDH2 was abrogated by RIPostC. Moreover, the effects of RIPostC on OGD/R-treated H9c2 cells were significantly reversed by ALDH2 silence. Finally, we found RIPostC-induced up-regulation of ALDH2 in OGD/R-treated cells could be bated by activation of PI3K and/or mTOR.CONCLUSIONS:
RIPostC exerted cardioprotective role against myocardial I/R both in vivo and in vitro. Up-regulation of ALDH2 might be a reason for the cardioprotection, and RIPostC might regulate ALDH2 expression via the PI3K/mTOR pathway.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão Miocárdica
/
Apoptose
/
Miócitos Cardíacos
/
Artéria Femoral
/
Pós-Condicionamento Isquêmico
/
Aldeído-Desidrogenase Mitocondrial
/
Infarto do Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur Rev Med Pharmacol Sci
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China