Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2α/ATF4 signaling pathway
BackgroundEndoplasmic 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...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1607606/full |
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| author | Siming Lin Siming Lin Siming Lin Jingying Wu Guili Lian Weibin Wu Weixiao Chen Ai Chen Li Luo Li Luo Li Luo Li Luo Li Luo Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie |
| author_facet | Siming Lin Siming Lin Siming Lin Jingying Wu Guili Lian Weibin Wu Weixiao Chen Ai Chen Li Luo Li Luo Li Luo Li Luo Li Luo Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie |
| author_sort | Siming Lin |
| collection | DOAJ |
| description | BackgroundEndoplasmic 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.MethodsGastrocnemius 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.ResultsOur 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.ConclusionThese findings highlight salubrinal’s potential as a therapeutic agent for muscle wasting conditions, particularly those related to oxidative stress and ERS. |
| format | Article |
| id | doaj-art-0141488e3c0f4170b92d1931a2cdda63 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-0141488e3c0f4170b92d1931a2cdda632025-08-20T03:30:20ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.16076061607606Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2α/ATF4 signaling pathwaySiming Lin0Siming Lin1Siming Lin2Jingying Wu3Guili Lian4Weibin Wu5Weixiao Chen6Ai Chen7Li Luo8Li Luo9Li Luo10Li Luo11Li Luo12Liangdi Xie13Liangdi Xie14Liangdi Xie15Liangdi Xie16Liangdi Xie17Department of Emergency, The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaDepartment of Emergency, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affliated Hospital, Fujian Medical University, Fuzhou, ChinaFujian Hypertension Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaClinical Research Center for Geriatric Hypertension Disease of Fujian Province, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Geriatrics, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaBranch of National Clinical Research Center for Aging and Medicine, The First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Geriatrics, National Regional Medical Center, Binhai Campus of the First Affliated Hospital, Fujian Medical University, Fuzhou, ChinaBackgroundEndoplasmic 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.MethodsGastrocnemius 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.ResultsOur 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.ConclusionThese findings highlight salubrinal’s potential as a therapeutic agent for muscle wasting conditions, particularly those related to oxidative stress and ERS.https://www.frontiersin.org/articles/10.3389/fphar.2025.1607606/fullsarcopeniaagingskeletal muscle atrophyendoplasmic reticulum stresssalubrinal |
| spellingShingle | Siming Lin Siming Lin Siming Lin Jingying Wu Guili Lian Weibin Wu Weixiao Chen Ai Chen Li Luo Li Luo Li Luo Li Luo Li Luo Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie Liangdi Xie Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2α/ATF4 signaling pathway Frontiers in Pharmacology sarcopenia aging skeletal muscle atrophy endoplasmic reticulum stress salubrinal |
| title | Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2α/ATF4 signaling pathway |
| title_full | Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2α/ATF4 signaling pathway |
| title_fullStr | Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2α/ATF4 signaling pathway |
| title_full_unstemmed | Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2α/ATF4 signaling pathway |
| title_short | Protective effects of Salubrinal against H2O2-induced muscle wasting via eIF2α/ATF4 signaling pathway |
| title_sort | protective effects of salubrinal against h2o2 induced muscle wasting via eif2α atf4 signaling pathway |
| topic | sarcopenia aging skeletal muscle atrophy endoplasmic reticulum stress salubrinal |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1607606/full |
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