Remote ischemic postconditioning protects the heart by upregulating ALDH2 expression levels through the PI3K/Akt signaling pathway.
Mol Med Rep
; 10(1): 536-42, 2014 Jul.
Article
em En
| MEDLINE
| ID: mdl-24736969
ABSTRACT
Remote ischemic postconditioning (RIPostC) has been demonstrated to protect the myocardium against ischemia/reperfusion (I/R) injury; however, the mediator and underlying mechanisms remain to be elucidated. It has been confirmed that aldehyde dehydrogenase 2 (ALDH2) is involved in the remote ischemic preconditioning pathway, but whether it is involved in RIPostC remains unknown. The aim of the present study was to determine whether increased ALDH2 expression levels were involved in the cardioprotective effect evoked by RIPostC via the phosphatidylinositol3kinase (PI3K)/Akt signaling pathway. Male Sprague Dawley rats (n=48) were randomly allocated into the following four groups Sham group, I/R group, RIPostC group, and RIPostC plus wortmannin group (RIPostC+Wort). With the exception of the Sham group, the anesthetized rats underwent 45 min of coronary artery occlusion followed by 180 min of reperfusion to mimic an I/R injury model. Hemodynamic parameters, including the mean arterial pressure and heart rate, were recorded, the infarct size was determined and the plasma lactate dehydrogenase (LDH) content and creatine kinase (CK) activity levels were measured. The expression levels of Bcl2 and Bax at the mRNA level and ALDH2, Akt, phosphoAkt (pAkt), caspase3 and cleaved caspase3 at the protein level in the left anterior myocardium were assessed. In the RIPostC group, the infarct size was reduced versus that of the I/R group. The plasma LDH content and CK activity levels were also reduced. The expression levels of ALDH2 protein were elevated, accompanied with increases in the levels of Bcl2/Bax and pAkt/Akt and a reduction in the levels of cleaved caspase3. When the PI3K inhibitor wortmannin was administered at reperfusion, the pAkt/Akt ratio was markedly reduced and associated with a reduction in the ALDH2 and Bcl2/Bax levels, and the cleaved caspase3 expression levels were elevated. In conclusion, ALDH2 may be an important mediator in the cardioprotection of RIPostC through the PI3K/Aktdependent signaling pathway.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article