1. Academic Validation
  2. Bisoprolol, a β1 antagonist, protects myocardial cells from ischemia-reperfusion injury via PI3K/AKT/GSK3β pathway

Bisoprolol, a β1 antagonist, protects myocardial cells from ischemia-reperfusion injury via PI3K/AKT/GSK3β pathway

  • Fundam Clin Pharmacol. 2020 Dec;34(6):708-720. doi: 10.1111/fcp.12562.
Jing Wang 1 Jing Liu 1 Liang Xie 1 Xiaomin Cai 1 Xiaohua Ma 1 Jianbin Gong 1
Affiliations

Affiliation

  • 1 Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, 305 East Zhongshan Rd., Nanjing, 210002, Jiangsu, China.
Abstract

The aim of this work was to explore whether bisoprolol plays a protective role in cardiomyocytes against ischemia-reperfusion injury via PI3K/Akt/ GSK3β pathway. We pretreated male Sprague Dawley (SD) rats with bisoprolol by oral administration prior to 0.5 h ischemia/4 h reperfusion. Myocardial infarct size and serum levels of cTnI and CK-MB were measured. In vitro, H9c2 cells were treated with hypoxia and reoxygenation, followed by measurement of cell viability, Apoptosis, ROS production, cytometry, activities of Akt, GSK3β, and p-38 in the presence and absence of GSK3β siRNA. We found that bisoprolol reduced infarct size from 44% in I/R group to 31% in treated group (P < 0.05). The levels of cTnI and CK-MB were decreased from 286 ± 7 pg/mL and 32.2 ± 2 ng/mL in I/R group to 196 ± 2 pg/mL and 19.6 ± 0.9 ng/mL in the treated group, respectively (P < 0.05). Bisoprolol also increased cell viability while decreased Apoptosis and ROS production in the treatment of hypoxia/ reoxygenation. Furthermore, bisoprolol increased Akt and GSK3β phosphorylation, an effect that was immediately eliminated by LY294002. GSK3β-specific siRNA experiment further confirmed that bisoprolol protected the myocardium against hypoxia/reoxygenation-induced injury via suppressing GSK3β activity. In conclusion, bisoprolol protected myocardium against ischemia-reperfusion injury via the PI3K/Akt/ GSK3β pathway.

Keywords

PI3K/AKT/GSK3β; bisoprolol; hypoxia/reoxygenation; ischemia/reperfusion.

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