ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Inflammation Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1607606
Protective Effects of Salubrinal Against H2O2-Induced Muscle Wasting via eIF2α/ATF4 Signaling Pathway
Provisionally accepted
- Fujian Medical University, Fuzhou, China
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Background: Endoplasmic reticulum stress (ERS) plays a critical role in skeletal muscle physiology and pathology, though the precise mechanisms remain unclear.Salubrinal, a selective inhibitor of eIF2α dephosphorylation, has been shown as a potential therapeutic agent for various conditions, but its effects on sarcopenia are not well understood. This study investigated the protective effects of salubrinal against H2O2-induced muscle cell injury and its impact on the eIF2α/ATF4 signaling pathway.Methods: Gastrocnemius muscle samples from aged mice were used and cultured C2C12 myotubes were also used to explore the effects of Salubrinal through Western blotting, immunofluorescence, and apoptosis assays.Results: Our results demonstrated that H2O2 treatment induced significant muscle cell damage, evidenced by reduced MHC1 expression and increased apoptosis. Salubrinal, in a concentration-dependent manner, mitigated these effects, preserving MHC1 expression and reducing apoptosis. Furthermore, salubrinal enhanced the expression of p-eIF2α and ATF4, suggesting that its protective effects are mediated through the eIF2α/ATF4 pathway.Conclusions: These findings highlight salubrinal's potential as a therapeutic agent for muscle wasting conditions, particularly those related to oxidative stress and ERS.
Keywords: Sarcopenia, Aging, skeletal muscle atrophy, Endoplasmic Reticulum Stress, salubrinal Sarcopenia, Salubrinal
Received: 07 Apr 2025; Accepted: 19 Jun 2025.
Copyright: © 2025 Lin, Wu, Lian, Wu, Chen, Chen, Luo and Xie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Siming Lin, Fujian Medical University, Fuzhou, China
Liangdi Xie, Fujian Medical University, Fuzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.