B-type natriuretic peptide attenuates endoplasmic reticulum stress in H9c2 cardiomyocytes underwent hypoxia/reoxygenation injury under high glucose/high fat conditions.

Exogenously administered B-type natriuretic peptide (BNP) has been shown to provide cardioprotection against various heart diseases. However, the underlying mechanisms remain elusive. This study explores whether BNP exerts its cardioprotection against hypoxia/reoxygenation (H/R) injury under high glucose/high fat (HG/HF) conditions in cardiac H9c2 cells and uncovers the underlying mechanisms. Our data revealed that BNP significantly increased the cell viability and decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK), with a maximal effect at the BNP concentration of 10 mol/L. In addition, by analyzing the activation of cleaved caspase-3 and by Annexin V-FITC/PI staining, we showed that BNP attenuated H/R-induced cell apoptosis in HG/HF conditions. Western blot analysis showed enhanced phosphorylation of protein kinase RNA (PKR)-like endoplastmic reticulum (ER) kinase (PERK) and eukaryotic initiation factor 2α (eIF2α)(one of the three main signaling pathways in endoplastmic reticulum (ER) stress), and increased expression of GRP78 and CHOP proteins (ER stress-related proteins) in H9c2 cells which underwent H/R in HG/HF conditions. Treatment with BNP or 8-Br-cGMP (an analog of cGMP) reversed this activation. However, this effect was significantly weakened by KT-5823, a selective cGMP-dependent protein kinase G (PKG) inhibitor. In addition, similar to BNP, treatment with a specific inhibitor of ER stress tauroursodeoxycholic acid (TUDCA) protected the cells against H/R injury exposed to HG/HF conditions. In conclusion, these findings demonstrated that BNP effectively protected cells against H/R injury under HG/HF conditions by inhibiting the ER stress via activation of the cGMP-PKG signaling pathway.