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; Ganggang Shi

doi:10.18632/oncotarget.5077

Oncotarget

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial, Introducing Oncotarget.

As of January 1, 2022, Oncotarget has shifted to a continuous publishing model. Papers will now be published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Subscribe to receive alerts once a paper has been published by Oncotarget.

Impact Journals, LLC is the publisher of Oncotarget: www.impactjournals.com.

Impact Journals is a member of the Wellcome Trust List of Compliant Publishers.

Impact Journals is a member of the Society for Scholarly Publishing.

On December 23, 2022, Oncotarget server experienced a DDoS attack. As a result, Oncotarget site was inaccessible for a few hours. Oncotarget team swiftly dealt with the situation and took it under control. This malicious action will be reported to the FBI.

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

PDF | HTML | Supplementary Files | How to cite

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

Metrics: PDF 2614 views | HTML 2295 views | ?

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.

All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 5077

Publication Alerts

Research Papers: Pathology:

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

Abstract