Notch signaling is involved in the antiapoptotic effects of liraglutide on rat H9c2 cardiomyocytes exposed to hypoxia followed by reoxygenation

Abstract

Objective: Liraglutide (Lir) protects cardiomyocytes against high glucose-induced myocardial damage. This study investigated whether Notch signaling participated in the antiapoptotic effects of Lir on rat H9c2 cardiomyocytes subjected to hypoxia followed by reoxygenation (H/R). Methods: We used H9c2 rat cardiomyocytes as a model of H/R and measured viability, apoptosis, and expression of the apoptotic genes Bax and Bcl-2 and Notch signaling genes Notch1 and Jagged1. Notch1 was depleted by siRNA to test the effect of Notch1 deficiency on the antiapoptotic effects of Lir on H/R-treated H9c2 cardiomyocytes. Results: After H/R treatment, viability was significantly decreased, and the apoptosis rate was greater in the H/R group than in the control (CT). Lir at 50, 100, and 200 nM significantly increased viability and decreased apoptosis in H/R-treated H9c2 cells. Treatment with 50 nM Lir for 2 hours before H/R significantly increased the expression levels of Notch1, Jagged1, and Bcl-2 compared with the CT levels. Bax was downregulated, which indicated that Lir activated Notch signaling and inhibited apoptosis. Notch1 depletion partially abolished the antiapoptotic effect of Lir on H/R-treated H9c2 cells by altering apoptotic gene expression. Conclusion: Lir activated Notch signaling, which was responsible for the antiapoptotic effect of Lir on H9c2 cardiomyocytes.