The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways
Previous research has demonstrated that melatonin protects against muscle damage while also improving the performance of injured muscle. However, its impact on healthy skeletal muscle remains largely unexplored. We exposed differentiated C2C12 myotubes to two melatonin concentrations (10 nM or 50 nM...
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Elsevier
2025-06-01
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| Series: | Experimental and Molecular Pathology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0014480025000152 |
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| author | Garth Wentley Russel J. Reiter Yong-Xiao Wang Gerald Maarman |
| author_facet | Garth Wentley Russel J. Reiter Yong-Xiao Wang Gerald Maarman |
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| description | Previous research has demonstrated that melatonin protects against muscle damage while also improving the performance of injured muscle. However, its impact on healthy skeletal muscle remains largely unexplored. We exposed differentiated C2C12 myotubes to two melatonin concentrations (10 nM or 50 nM). The 10 nM concentration did not affect any of the mitochondrial respiration parameters. Whereas 50 nM concentration reduced mitochondrial complex II-linked oxidative phosphorylation (OXPHOS), electron transfer system (ETS) capacity, the contribution of complex II to ETS, and residual oxygen consumption (ROX). Neither concentration influenced the mitochondrial coupling control ratios, nor the coupling control efficiency ratios. Furthermore, neither concentration affected ATP production but reduced superoxide dismutase activity. The 50 nM increased catalase activity without affecting autophagy or citrate synthase activity. Moreover, 50 nM reduced activated JAK2 and STAT3 protein expression, while 10 nM reduced JAK2 without affecting STAT3. Th 50 nM increased activated AKT and ERK1/2 expression with no effect on p38 or PGC1-α expression. Our data suggests that melatonin (50 nM) triggers an oxygen-sparing effect on mitochondrial respiration, which is mediated via its antioxidant actions and its ability to enhance pro-survival pathways. Therefore, melatonin intake may have ergogenic effects on healthy muscles, in the absence of pathology, e.g., consumption before sporting events or physical exercise may aid in the reduction of oxidative stress often associated with such activities. However, this is an in vitro study, and therefore, the clinical relevance of the data should be considered with caution. |
| format | Article |
| id | doaj-art-b8615fcd0c72427299a9f7fc4d4d53a5 |
| institution | OA Journals |
| issn | 1096-0945 |
| language | English |
| publishDate | 2025-06-01 |
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| series | Experimental and Molecular Pathology |
| spelling | doaj-art-b8615fcd0c72427299a9f7fc4d4d53a52025-08-20T02:05:43ZengElsevierExperimental and Molecular Pathology1096-09452025-06-0114210496610.1016/j.yexmp.2025.104966The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathwaysGarth Wentley0Russel J. Reiter1Yong-Xiao Wang2Gerald Maarman3CARMA: Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South AfricaDepartment of Cellular and Structural Biology, UT Health San Antonio, San Antonio, TX, United StatesDepartment of Molecular & Cellular Physiology, Albany Medical College, Albany, NY, United StatesCARMA: Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Stellenbosch University, Cape Town 8000, South Africa; Corresponding author at: CARMA: Centre for Cardio-Metabolic Research in Africa, University of Stellenbosch, 3rd floor BMRI Building, Tygerberg Medical School, Francie van Zijl Avenue, Cape Town 8000, South Africa.Previous research has demonstrated that melatonin protects against muscle damage while also improving the performance of injured muscle. However, its impact on healthy skeletal muscle remains largely unexplored. We exposed differentiated C2C12 myotubes to two melatonin concentrations (10 nM or 50 nM). The 10 nM concentration did not affect any of the mitochondrial respiration parameters. Whereas 50 nM concentration reduced mitochondrial complex II-linked oxidative phosphorylation (OXPHOS), electron transfer system (ETS) capacity, the contribution of complex II to ETS, and residual oxygen consumption (ROX). Neither concentration influenced the mitochondrial coupling control ratios, nor the coupling control efficiency ratios. Furthermore, neither concentration affected ATP production but reduced superoxide dismutase activity. The 50 nM increased catalase activity without affecting autophagy or citrate synthase activity. Moreover, 50 nM reduced activated JAK2 and STAT3 protein expression, while 10 nM reduced JAK2 without affecting STAT3. Th 50 nM increased activated AKT and ERK1/2 expression with no effect on p38 or PGC1-α expression. Our data suggests that melatonin (50 nM) triggers an oxygen-sparing effect on mitochondrial respiration, which is mediated via its antioxidant actions and its ability to enhance pro-survival pathways. Therefore, melatonin intake may have ergogenic effects on healthy muscles, in the absence of pathology, e.g., consumption before sporting events or physical exercise may aid in the reduction of oxidative stress often associated with such activities. However, this is an in vitro study, and therefore, the clinical relevance of the data should be considered with caution.http://www.sciencedirect.com/science/article/pii/S0014480025000152MelatoninC2C12 myotubesSkeletal muscleMitochondrial function |
| spellingShingle | Garth Wentley Russel J. Reiter Yong-Xiao Wang Gerald Maarman The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways Experimental and Molecular Pathology Melatonin C2C12 myotubes Skeletal muscle Mitochondrial function |
| title | The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways |
| title_full | The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways |
| title_fullStr | The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways |
| title_full_unstemmed | The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways |
| title_short | The effects of melatonin on differentiated C2C12 myotubes in the absence of pathology: An oxygen-sparing action and enhancement of pro-survival signalling pathways |
| title_sort | effects of melatonin on differentiated c2c12 myotubes in the absence of pathology an oxygen sparing action and enhancement of pro survival signalling pathways |
| topic | Melatonin C2C12 myotubes Skeletal muscle Mitochondrial function |
| url | http://www.sciencedirect.com/science/article/pii/S0014480025000152 |
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