5′-Cytimidine Monophosphate Ameliorates H<sub>2</sub>O<sub>2</sub>-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway
Age-related muscle atrophy (sarcopenia), characterized by reduced skeletal muscle mass and muscle strength, is becoming increasingly prevalent worldwide, which is especially true for older people, and can seriously damage health and quality of life in older adults. This study aims to investigate the...
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MDPI AG
2024-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/13/2/249 |
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| author | Xin Wu Na Zhu Lixia He Meihong Xu Yong Li |
| author_facet | Xin Wu Na Zhu Lixia He Meihong Xu Yong Li |
| author_sort | Xin Wu |
| collection | DOAJ |
| description | Age-related muscle atrophy (sarcopenia), characterized by reduced skeletal muscle mass and muscle strength, is becoming increasingly prevalent worldwide, which is especially true for older people, and can seriously damage health and quality of life in older adults. This study aims to investigate the beneficial effects of 5′-cytimidine monophosphate (CMP) on H<sub>2</sub>O<sub>2</sub>-induced muscular atrophy in C2C12 myotubes. C2C12 myotubes were treated with H<sub>2</sub>O<sub>2</sub> in the presence and absence of CMP and the changes in the anti-oxidation, mitochondrial functions, and expression of sarcopenia-related proteins were observed. Immunofluorescence analysis showed that CMP significantly increased the diameter of myotubes. We found that CMP could increase the activity of antioxidant enzymes and improve mitochondrial dysfunction, as well as reduce inflammatory cytokine levels associated with sarcopenia. RNA-seq analysis showed that CMP could relieve insulin resistance and promote protein digestion and absorption. Western blot analysis further confirmed that CMP could promote the activation of the IRS-1/Akt/S6K signaling pathway and decrease the expression of MuRF1 and Atrogin-1, which are important markers of muscle atrophy. The above results suggest that CMP protects myotubes from H<sub>2</sub>O<sub>2</sub>-induced atrophy and that its potential mechanism is associated with activating the IRS-1/Akt/S6K pathway to promote protein synthesis by improving mitochondrial dysfunction and insulin resistance. These results indicate that CMP can improve aging-related sarcopenia. |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-07T22:44:29Z |
| publishDate | 2024-02-01 |
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| series | Antioxidants |
| spelling | doaj.art-56b9d9647ec84216ae5bfeccde7412662024-02-23T15:05:37ZengMDPI AGAntioxidants2076-39212024-02-0113224910.3390/antiox130202495′-Cytimidine Monophosphate Ameliorates H<sub>2</sub>O<sub>2</sub>-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K PathwayXin Wu0Na Zhu1Lixia He2Meihong Xu3Yong Li4Department of Nutrition and Food Hygiene, School of Public Health, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Nutrition and Food Hygiene, College of Public Health, Inner Mongolia Medical University, Hohhot 010059, ChinaDivision of Molecular and Cellular Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USADepartment of Nutrition and Food Hygiene, School of Public Health, Peking University Health Science Center, Beijing 100191, ChinaDepartment of Nutrition and Food Hygiene, School of Public Health, Peking University Health Science Center, Beijing 100191, ChinaAge-related muscle atrophy (sarcopenia), characterized by reduced skeletal muscle mass and muscle strength, is becoming increasingly prevalent worldwide, which is especially true for older people, and can seriously damage health and quality of life in older adults. This study aims to investigate the beneficial effects of 5′-cytimidine monophosphate (CMP) on H<sub>2</sub>O<sub>2</sub>-induced muscular atrophy in C2C12 myotubes. C2C12 myotubes were treated with H<sub>2</sub>O<sub>2</sub> in the presence and absence of CMP and the changes in the anti-oxidation, mitochondrial functions, and expression of sarcopenia-related proteins were observed. Immunofluorescence analysis showed that CMP significantly increased the diameter of myotubes. We found that CMP could increase the activity of antioxidant enzymes and improve mitochondrial dysfunction, as well as reduce inflammatory cytokine levels associated with sarcopenia. RNA-seq analysis showed that CMP could relieve insulin resistance and promote protein digestion and absorption. Western blot analysis further confirmed that CMP could promote the activation of the IRS-1/Akt/S6K signaling pathway and decrease the expression of MuRF1 and Atrogin-1, which are important markers of muscle atrophy. The above results suggest that CMP protects myotubes from H<sub>2</sub>O<sub>2</sub>-induced atrophy and that its potential mechanism is associated with activating the IRS-1/Akt/S6K pathway to promote protein synthesis by improving mitochondrial dysfunction and insulin resistance. These results indicate that CMP can improve aging-related sarcopenia.https://www.mdpi.com/2076-3921/13/2/2495′-cytimidine monophosphatesarcopeniamuscular atrophyaging |
| spellingShingle | Xin Wu Na Zhu Lixia He Meihong Xu Yong Li 5′-Cytimidine Monophosphate Ameliorates H<sub>2</sub>O<sub>2</sub>-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway Antioxidants 5′-cytimidine monophosphate sarcopenia muscular atrophy aging |
| title | 5′-Cytimidine Monophosphate Ameliorates H<sub>2</sub>O<sub>2</sub>-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway |
| title_full | 5′-Cytimidine Monophosphate Ameliorates H<sub>2</sub>O<sub>2</sub>-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway |
| title_fullStr | 5′-Cytimidine Monophosphate Ameliorates H<sub>2</sub>O<sub>2</sub>-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway |
| title_full_unstemmed | 5′-Cytimidine Monophosphate Ameliorates H<sub>2</sub>O<sub>2</sub>-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway |
| title_short | 5′-Cytimidine Monophosphate Ameliorates H<sub>2</sub>O<sub>2</sub>-Induced Muscular Atrophy in C2C12 Myotubes by Activating IRS-1/Akt/S6K Pathway |
| title_sort | 5 cytimidine monophosphate ameliorates h sub 2 sub o sub 2 sub induced muscular atrophy in c2c12 myotubes by activating irs 1 akt s6k pathway |
| topic | 5′-cytimidine monophosphate sarcopenia muscular atrophy aging |
| url | https://www.mdpi.com/2076-3921/13/2/249 |
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