Apoptotic Protease Activating Factor-1 Inhibitor Mitigates Myocardial Ischemia Injury via Disturbing Procaspase-9 Recruitment by Apaf-1
Joint Authors
Zhang, Qiuyan
Liu, Xinhua
Wang, Ying
Zhong, Liangjie
Lin, Mingshen
Luo, Xiaoling
Liu, Siyu
Xu, Peng
Zhu, Yi Zhun
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-11-27
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
(2S,3S,4S,5R,6R)-6-(4-((4-guanidinobutoxy)carbonyl)-2,6-dihydroxyphenoxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid (ZYZ-488) was discovered as a novel inhibitor of apoptotic protease activating factor-1 (Apaf-1).
In present work, a surface plasmon resonance (SPR) assay confirms the direct binding between ZYZ-488 and Apaf-1 and this interaction was found to be able to block the recruitment of procaspase-9 by Apaf-1.
This study also shows that the treatment of MI (myocardial infarction) mice with this novel Apaf-1 inhibitor remarkably reduces the infarct size, improves cardiac functions, and attenuates the histopathology changes caused by MI.
Meanwhile, here it is shown that ZYZ-488 decreases myocardial enzyme release, inhibits cardiomyocyte apoptosis, and suppresses the activation of the downstream cascade of caspases.
Moreover, in silico prediction validated the drug-like properties of ZYZ-488.
In conclusion, our findings present the first piece of evidence indicating the interaction between Apaf-1 and procaspase-9 as a novel therapeutic target in myocardial infarction and suggesting ZYZ-488 as a promising therapeutic option for myocardial infarction disease.
American Psychological Association (APA)
Wang, Ying& Zhang, Qiuyan& Zhong, Liangjie& Lin, Mingshen& Luo, Xiaoling& Liu, Siyu…[et al.]. 2017. Apoptotic Protease Activating Factor-1 Inhibitor Mitigates Myocardial Ischemia Injury via Disturbing Procaspase-9 Recruitment by Apaf-1. Oxidative Medicine and Cellular Longevity،Vol. 2017, no. 2017, pp.1-9.
https://search.emarefa.net/detail/BIM-1196715
Modern Language Association (MLA)
Wang, Ying…[et al.]. Apoptotic Protease Activating Factor-1 Inhibitor Mitigates Myocardial Ischemia Injury via Disturbing Procaspase-9 Recruitment by Apaf-1. Oxidative Medicine and Cellular Longevity No. 2017 (2017), pp.1-9.
https://search.emarefa.net/detail/BIM-1196715
American Medical Association (AMA)
Wang, Ying& Zhang, Qiuyan& Zhong, Liangjie& Lin, Mingshen& Luo, Xiaoling& Liu, Siyu…[et al.]. Apoptotic Protease Activating Factor-1 Inhibitor Mitigates Myocardial Ischemia Injury via Disturbing Procaspase-9 Recruitment by Apaf-1. Oxidative Medicine and Cellular Longevity. 2017. Vol. 2017, no. 2017, pp.1-9.
https://search.emarefa.net/detail/BIM-1196715
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1196715