Year-end Sale % OFF 
Abstract
Mitochondrial dysfunction and endoplasmic reticulum (ER) stress contribute to postischemic myocardial damage, but the upstream regulatory mechanisms have not been identified. In this study, we analyzed the role of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) in the regulation of mitochondrial function and ER stress in hypoxic cardiomyocytes. Our results show that MKP-1 overexpression sustains viability and reduces hypoxia-induced apoptosis among H9C2 cardiomyocytes. MKP-1 overexpression attenuates ER stress and expression of ER stress genes and improves mitochondrial function in hypoxia-treated H9C2 cells. MKP-1 overexpression also increases ATP production and mitochondrial respiration and attenuates mitochondrial oxidative damage in hypoxic cardiomyocytes. Moreover, our results demonstrate that ERK and JNK are the downstream signaling targets of MKP-1 and that MKP-1 overexpression activates ERK, while it inhibits JNK. Inhibition of ERK reduces the ability of MKP-1 to preserve mitochondrial function and ER homeostasis in hypoxic cardiomyocytes. These results show that MKP-1 plays an essential role in the regulation of mitochondrial function and ER stress in hypoxic H9C2 cardiomyocytes through normalization of the ERK pathway and suggest that MKP-1 may serve as a novel target for the treatment of postischemic myocardial injury.
Highlights
Myocardial ischemia and/or hypoxia are common clinical diseases, which cause serious harm to the body, tissues, and organs [1, 2]
To investigate the possible cardioprotective function of MKP-1 in postischemic myocardial damage, we first analyzed cell viability in hypoxia-treated cardiomyocytes transfected with MKP-1 adenovirus
The number of apoptotic cardiomyocytes rapidly increased after exposure to hypoxia (Figures 1(c) and 1(d)), but MKP-1 overexpression decreased the ratio of apoptotic cardiomyocytes (Figures 1(c) and 1(d))
Summary
Myocardial ischemia and/or hypoxia are common clinical diseases, which cause serious harm to the body, tissues, and organs [1, 2]. Myocardial damage, necrosis, and arrhythmia caused by myocardial ischemia and hypoxia rank first in the incidence of heart disease, which is one of the main problems facing the world today [3, 4]. Hypoxia is the main factor of myocardial ischemia and plays a vital role in causing ischemic heart disease damage [5, 6]. After the blood supply is restored, the ischemic myocardium regains normal perfusion, but additional damage occurs to the postischemic myocardium tissues [9, 10]. A series of pathological changes occur during the ischemic period including changes in myocardial ultrastructure, energy metabolism, malignant arrhythmia, mitochondria damage, and endoplasmic reticulum (ER) stress [11,12,13,14,15]. The mechanisms underlying the pathogenesis of myocardial postischemia damage are not fully understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
