Down-modulation of endoplasmic reticulum stressinitiated apoptosis by huperzine A in isoproterenolprovoked myocardial infarction rat model: Role of Nrf2/HO- 1 signaling axis

Abstract

Purpose: To investigate the myocardial protective effect of huperzine A (HPA), a sesquiterpene alkaloid, in a rat model of isoproterenol (ISP)- provoked MI and ER stress.Methods: Three groups of rats were used: control, ISP and ISP+HPA groups. The following indices were assayed using standard protocols: oxidative stress parameters, including NADPH oxidase 4 (NOX4), reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1); indices of calcium homeostasis, namely, sarcoplasmic and endoplasmic reticulum calcium ATPase isoform 2a (SERCA2a); ER stress parameters, viz, protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), glucose-regulated protein 78 (GRP78), and C/EBP homologous protein (CHOP); and indices of apoptosis, i.e., B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-12].Results: Oxidative/ER stress and cardiomyocyte apoptosis were up-modulated (p < 0.05), while SERCA2a, a key calcium handling channel, was downmodulated in the ISP group (p < 0.05). In contrast, HPA treatment ameliorated these ISP-induced myocardial aberrations. (p < 0.05).Conclusion: These results indicate that HPA might be a potential therapeutic candidate for MI and associated cardiac problems. Keywords: Caspase-12, ER stress, Huperzine A, Myocardial infarction, SERCA2a