Oncotarget

Research Papers: Pathology:

N-n-butyl haloperidol iodide protects cardiomyocytes against hypoxia/reoxygenation injury by inhibiting autophagy

Bin Wang _, Shuping Zhong, Fuchun Zheng, Yanmei Zhang, Fenfei Gao, Yicun Chen, Binger Lu, Han Xu and Ganggang Shi

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Oncotarget. 2015; 6:24709-24721. https://doi.org/10.18632/oncotarget.5077

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Abstract

Bin Wang1, Shuping Zhong2, Fuchun Zheng3, Yanmei Zhang1, Fenfei Gao1, Yicun Chen1, Binger Lu1, Han Xu1, Ganggang Shi1,4

1Department of Pharmacology, Shantou University Medical College, Shantou, 515041 Guangdong, China

2Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA

3Department of Pharmacy, The First Affiliated Hospital, Shantou University Medical College, Shantou, 515041 Guangdong, China

4Department of Cardiovascular Diseases, The First Affiliated Hospital, Shantou University Medical College, Shantou, 515041 Guangdong, China

Correspondence to:

Ganggang Shi, e-mail: [email protected]

Keywords: Pathology Section, autophagy, N-n-butyl haloperidol iodide, hypoxia/reoxygenation, apoptosis, cardiomyocytes

Received: June 05, 2015     Accepted: August 20, 2015     Published: September 02, 2015

ABSTRACT

N-n-butyl haloperidol iodide (F2), a novel compound derived from haloperidol, protects against the damaging effects of ischemia/reperfusion (I/R) injury in vitro and in vivo. In this study, we hypothesized the myocardial protection of F2 on cardiomyocyte hypoxia/reoxygenation (H/R) injury is mediated by inhibiting autophagy in H9c2 cells. The degree of autophagy by treatment with F2 exposed to H/R in H9c2 cell was characterized by monodansylcadaverine, transmission electron microscopy, and expression of autophagy marker protein LC3. Our results indicated that treatment with F2 inhibited autophagy in H9c2 cells exposed to H/R. 3-methyladenine, an inhibitor of autophagy, suppressed H/R-induced autophagy, and decreased apoptosis, whereas rapamycin, a classical autophagy sensitizer, increased autophagy and apoptosis. Mechanistically, macrophage migration inhibitory factor (MIF) was inhibited by F2 treatment after H/R. Accordingly, small interfering RNA (siRNA)-mediated MIF knockdown decreased H/R-induced autophagy. In summary, F2 protects cardiomyocytes during H/R injury through suppressing autophagy activation. Our results provide a new mechanistic insight into a functional role of F2 against H/R-induced cardiomyocyte injury and death.


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