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Changes in AMPK alpha and Ubiquitin Ligases in Myocyte Reverse Remodeling after Surgical Ventricular Reconstruction in rats with ischemic cardiomyopathy

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Title: Changes in AMPK alpha and Ubiquitin Ligases in Myocyte Reverse Remodeling after Surgical Ventricular Reconstruction in rats with ischemic cardiomyopathy
Authors: Shingu, Yasushige Browse this author →KAKEN DB
Hieda, Tetsuya Browse this author
Sugimoto, Satoshi Browse this author
Asai, Hidetsugu Browse this author
Yamakawa, Tomoji Browse this author
Wakasa, Satoru Browse this author →KAKEN DB
Keywords: Atrogin-1
Murf-1
AMPK alpha
Myocyte reverse remodeling
Surgical ventricular reconstruction
Issue Date: 1-Jun-2022
Publisher: Springer
Journal Title: Molecular Biology Reports
Volume: 49
Issue: 6
Start Page: 4885
End Page: 4892
Publisher DOI: 10.1007/s11033-022-07347-8
Abstract: Background The change in myocardial protein degradation systems after ventricular unloading has been unknown. We aimed to evaluate the anti-hypertrophic protein adenosine monophosphate-activated protein kinase (AMPK) and two major protein degradation systems (ubiquitin proteasome system and autophagy) in a model of surgical ventricular reconstruction (SVR) in rats with ischemic cardiomyopathy. Methods and Results Rats were randomized into the following groups: sham/sham (control group), myocardial infarction (MI)/sham (sham group) and MI/SVR (SVR group), with an interval of 4 weeks. Two (early, n = 5 for each) and 28 days (late, n=5 for each) after SVR, ventricular size, and wall stress were assessed. Myocyte area, protein expression of AMPK alpha and autophagy markers, and gene expression of ubiquitin ligases (Atrogin-1 and Murf-1) were evaluated in the late phase. In the early phase, left ventricular dimensions and wall stress were smaller in the SVR group than in the sham group, whereas they were comparable in the late period. Myocyte area in the SVR group was reduced to the value in the control group, while it was larger in the sham group than in the control group. Total-AMPK alpha, p-AMPK alpha, and AMPK alpha phosphorylation rates were higher, and Atrogin-1 and Murf-1 were lower in the SVR group than in the sham group, while the autophagy markers were not different between the groups. p-AMPK alpha had strong negative correlations with myocyte area, Atrogin-1, and Murf-1. Conclusions In myocyte reverse remodeling after SVR, AMPK alpha phosphorylation increased in association with reduced gene expression of ubiquitin ligases.
Rights: This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s11033-022-07347-8
Type: article (author version)
URI: http://hdl.handle.net/2115/89789
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 新宮 康栄

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