Regulation of VDAC1 contributes to the cardioprotective effects of penehyclidine hydrochloride during myocardial ischemia/reperfusion

Journal Article · Fri Jun 15 04:00:00 EDT 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2018.04.004· OSTI ID:23082354

Lin, Duomao; Cui, Boqun; Ren, Jiayue; Ma, Jun ^[1]

---

1. Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Road, Beijing, 100029 (China)

Penehyclidine hydrochloride (PHC) preconditioning can alleviate myocardial ischemia/reperfusion (I/R) injury and inhibits the upregulation of voltage-dependent anion channel 1 (VDAC1) during I/R. To validate that VDAC1 is a bona fide target of PHC for the protection against myocardial I/R injury, VDAC1 expression construct was delivered by lentiviruses into rat left ventricular myocardium before PHC preconditioning and myocardial I/R. Overexpression of VDAC1 exacerbated cardiac dysfunction and myocardial injury following I/R, and abolished the cardioprotective effect of PHC during I/R injury. Moreover, VDAC1 overexpression with myocardial I/R further increased cytochrome c release from mitochondria to cytoplasm, elevated the levels of cleaved caspase-3 and Bax, and decreased the level of Bcl-2 as compared with I/R alone, and PHC-mediated inhibition of mitochondria-dependent apoptosis during myocardial I/R was abolished by VDAC1 overexpression. In addition, VDAC1 was overexpressed in H9c2 cardiomyocytes undergoing anoxia/reoxygenation (A/R) with or without PHC pretreatment. The in vitro results showed that overexpression of VDAC1 further reduced mitochondrial membrane potential, increased mitochondrial membrane permeability and enhanced mitochondria-dependent apoptosis in H9c2 cells after A/R, and VDAC1 overexpression abrogated the protective effect of PHC on the mitochondrial function and integrity during A/R. In conclusion, exogenous overexpression of VDAC1 during myocardial I/R inhibits the cardioprotective effects of PHC. These effects may be associated with the suppression of VDAC1 expression.

• OSTI ID: 23082354
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 367; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANOXIA
APOPTOSIS
CYTOCHROMES
CYTOPLASM
ISCHEMIA
MEMBRANES
MITOCHONDRIA
MYOCARDIUM
RATS