Cox-2 Inhibition Protects against HypoxiaReoxygenation-Induced Cardiomyocyte Apoptosis via Akt-Dependent Enhancement of iNOS Expression
Joint Authors
Irwin, Michael G.
Li, Haobo
Pang, Lei
Cai, Yin
Tang, Eva Hoi Ching
Ma, Haichun
Yan, Dan
Kosuru, Ramoji
Xia, Zhengyuan
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-10-04
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
The present study explored the potential causal link between ischemia-driven cyclooxygenase-2 (COX-2) expression and enhanced apoptosis during myocardial ischemia/reperfusion (I/R) by using H9C2 cardiomyocytes and primary rat cardiomyocytes subjected to hypoxia/reoxygenation (H/R).
The results showed that H/R resulted in higher COX-2 expression than that of controls, which was prevented by pretreatment with Helenalin (NFκB specific inhibitor).
Furthermore, pretreatment with NS398 (COX-2 specific inhibitor) significantly attenuated H/R-induced cell injury [lower lactate dehydrogenase (LDH) leakage and enhanced cell viability] and apoptosis (higher Bcl2 expression and lower level of cleaved caspases-3 and TUNEL-positive cells) in cardiomyocytes.
The amelioration of posthypoxic apoptotic cell death was paralleled by significant attenuation of H/R-induced increases in proinflammatory cytokines [interleukin 6 (IL6) and tumor necrosis factor (TNFα)] and reactive oxygen species (ROS) production and by higher protein expression of phosphorylated Akt and inducible nitric oxide synthase (iNOS) and enhanced nitric oxide production.
Moreover, the application of LY294002 (Akt-specific inhibitor) or 1400W (iNOS-selective inhibitor) cancelled the cellular protective effects of NS398.
Findings from the current study suggest that activation of NFκB during cardiomyocyte H/R induces the expression of COX-2 and that higher COX-2 expression during H/R exacerbates cardiomyocyte H/R injury via mechanisms that involve cross talks among inflammation, ROS, and Akt/iNOS/NO signaling.
American Psychological Association (APA)
Pang, Lei& Cai, Yin& Tang, Eva Hoi Ching& Yan, Dan& Kosuru, Ramoji& Li, Haobo…[et al.]. 2016. Cox-2 Inhibition Protects against HypoxiaReoxygenation-Induced Cardiomyocyte Apoptosis via Akt-Dependent Enhancement of iNOS Expression. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-17.
https://search.emarefa.net/detail/BIM-1113813
Modern Language Association (MLA)
Pang, Lei…[et al.]. Cox-2 Inhibition Protects against HypoxiaReoxygenation-Induced Cardiomyocyte Apoptosis via Akt-Dependent Enhancement of iNOS Expression. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-17.
https://search.emarefa.net/detail/BIM-1113813
American Medical Association (AMA)
Pang, Lei& Cai, Yin& Tang, Eva Hoi Ching& Yan, Dan& Kosuru, Ramoji& Li, Haobo…[et al.]. Cox-2 Inhibition Protects against HypoxiaReoxygenation-Induced Cardiomyocyte Apoptosis via Akt-Dependent Enhancement of iNOS Expression. Oxidative Medicine and Cellular Longevity. 2016. Vol. 2016, no. 2016, pp.1-17.
https://search.emarefa.net/detail/BIM-1113813
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1113813