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Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor

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Abstract
Background: Despite clinical evidence indicating poor muscle health in subjects with primary aldosteronism (PA), it is still unclear whether the role of aldosterone in muscle metabolism is direct or mediated indirectly via factors, such as electrolyte imbalance or impaired glucose uptake. As one approach to clarify this issue, we investigated the effect of aldosterone on in vitro myogenesis and the potential mechanism explaining it. Methods: Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Immunofluorescence, quantitative reverse transcription polymerase chain reaction, Western blot, viability, and migration analyses were performed for experimental research. Results: Recombinant aldosterone treatment suppressed muscle differentiation from mouse C2C12 myoblasts in a dose-dependent manner, and consistently reduced the expression of myogenic differentiation markers. Furthermore, aldosterone significantly increased intracellular reactive oxygen species (ROS) levels in myotubes, and treatment with N-acetyl cysteine, a potent biological thiol antioxidant, reversed the decrease of myotube area, myotube area per myotube, nucleus number per myotube, and fusion index due to aldosterone through decreasing oxidative stress. A binding enzyme-linked immunosorbent assay confirmed that mineralocorticoid receptor (MR) interacted with aldosterone in C2C12 myoblasts, while eplerenone, an MR inhibitor, blocked aldosterone-stimulated intracellular ROS generation during myogenesis and markedly attenuated the suppression of in vitro myogenesis by aldosterone. Conclusion: These findings support the hypothesis that hypersecretion of aldosterone, like PA, directly contributes to muscular deterioration and suggest that antioxidants and/or MR antagonists could be effective therapeutic options to reduce the risk of sarcopenia in these patients.
Author(s)
이진영김다애최은아이윤선박소정김범준
Issued Date
2021
Type
Article
Keyword
AldosteroneSarcopeniaMuscle developmentReceptorsmineralocorticoidOxidative stress
DOI
10.3803/EnM.2021.1108
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8092
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_kiss_primary_3900117&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Aldosterone%20Inhibits%20In%20Vitro%20Myogenesis%20by%20Increasing%20Intracellular%20Oxidative%20Stress%20via%20Mineralocorticoid%20Receptor&offset=0&pcAvailability=true
Publisher
ENDOCRINOLOGY AND METABOLISM
Location
대한민국
Language
영어
ISSN
2093-596X
Citation Volume
36
Citation Number
4
Citation Start Page
865
Citation End Page
874
Appears in Collections:
Medicine > Medicine
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