1,25-Dihydroxyvitamin D Decreases Tertiary Butyl-Hydrogen Peroxide-Induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle Cells
Enhanced oxidative stress has been associated with muscle mitochondrial changes and metabolic disorders. Thus, it might be a good strategy to decrease oxidative stress and improve mitochondrial changes in skeletal muscle. In the present study, we investigate the role of the most biologically active...
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MDPI AG
2019-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/21/3903 |
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| author | Eugene Chang |
| author_facet | Eugene Chang |
| author_sort | Eugene Chang |
| collection | DOAJ |
| description | Enhanced oxidative stress has been associated with muscle mitochondrial changes and metabolic disorders. Thus, it might be a good strategy to decrease oxidative stress and improve mitochondrial changes in skeletal muscle. In the present study, we investigate the role of the most biologically active metabolite of vitamin D, 1,25-dihyroxyvitamin D (1,25(OH)2D) in oxidative stress and mitochondrial changes in tertiary butyl-hydrogen (tBHP)-treated C2C12 muscle cells. Differentiated C2C12 muscle cells were pretreated with tBHP, followed by 1,25(OH)2D for additional 24 h. An exogenous inducer of oxidative stress, tBHP significantly increased oxidative stress, lipid peroxidation, intracellular damage, and cell death which were reversed by 1,25(OH)2D in C2C12 myotubes. 1.25(OH)2D improves tBHP-induced mitochondrial morphological changes such as swelling, irregular cristae, and smaller size and number, as observed by transmission electron microscope. In addition, 1,25(OH)2D treatment increases mtDNA contents as well as gene expression involved in mitochondrial biogenesis such as PGC1α, NRF1, and Tfam. Significant increments in mRNA levels related to antioxidant enzymes such as Nrf2, HMOX1, and TXNRD1, myogenic differentiation markers including myoglobin, muscle creatine kinase (MCK), and MHCІ and ІІ, and vitamin D metabolism such as CYP24, CYP27, and vitamin D receptor (VDR) were found in 1,25(OH)2D-treated myotubes. Moreover, upon t-BHP-induced oxidative stress, significant incremental changes in nicotinamide adenine dinucleotide (NAD) levels, activities of AMP-activated protein kinase (AMPK)/sirtulin 1 (SIRT1), and SIRT1 expression were noted in 1,25(OH)2D-treated C2C12 muscle cells. Taken together, these results suggest the observed potent inhibitory effect of 1,25(OH)2D on muscle oxidative stress and mitochondrial dynamics might be at least involved in the activation of AMPK and SIRT1 activation in muscle cells. |
| first_indexed | 2024-12-10T21:11:14Z |
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| language | English |
| last_indexed | 2024-12-10T21:11:14Z |
| publishDate | 2019-10-01 |
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| spelling | doaj.art-a1ccff1a58f844818552e2c4530bb5882022-12-22T01:33:29ZengMDPI AGMolecules1420-30492019-10-012421390310.3390/molecules24213903molecules242139031,25-Dihydroxyvitamin D Decreases Tertiary Butyl-Hydrogen Peroxide-Induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle CellsEugene Chang0Department of Nutritional Science and Food Management, Ewha Womans University, Seoul 03760, KoreaEnhanced oxidative stress has been associated with muscle mitochondrial changes and metabolic disorders. Thus, it might be a good strategy to decrease oxidative stress and improve mitochondrial changes in skeletal muscle. In the present study, we investigate the role of the most biologically active metabolite of vitamin D, 1,25-dihyroxyvitamin D (1,25(OH)2D) in oxidative stress and mitochondrial changes in tertiary butyl-hydrogen (tBHP)-treated C2C12 muscle cells. Differentiated C2C12 muscle cells were pretreated with tBHP, followed by 1,25(OH)2D for additional 24 h. An exogenous inducer of oxidative stress, tBHP significantly increased oxidative stress, lipid peroxidation, intracellular damage, and cell death which were reversed by 1,25(OH)2D in C2C12 myotubes. 1.25(OH)2D improves tBHP-induced mitochondrial morphological changes such as swelling, irregular cristae, and smaller size and number, as observed by transmission electron microscope. In addition, 1,25(OH)2D treatment increases mtDNA contents as well as gene expression involved in mitochondrial biogenesis such as PGC1α, NRF1, and Tfam. Significant increments in mRNA levels related to antioxidant enzymes such as Nrf2, HMOX1, and TXNRD1, myogenic differentiation markers including myoglobin, muscle creatine kinase (MCK), and MHCІ and ІІ, and vitamin D metabolism such as CYP24, CYP27, and vitamin D receptor (VDR) were found in 1,25(OH)2D-treated myotubes. Moreover, upon t-BHP-induced oxidative stress, significant incremental changes in nicotinamide adenine dinucleotide (NAD) levels, activities of AMP-activated protein kinase (AMPK)/sirtulin 1 (SIRT1), and SIRT1 expression were noted in 1,25(OH)2D-treated C2C12 muscle cells. Taken together, these results suggest the observed potent inhibitory effect of 1,25(OH)2D on muscle oxidative stress and mitochondrial dynamics might be at least involved in the activation of AMPK and SIRT1 activation in muscle cells.https://www.mdpi.com/1420-3049/24/21/3903adenosine monophosphate-activated protein kinase (ampk)musclemitochondriaoxidative stresssirtuin 1 (sirt1)vitamin d |
| spellingShingle | Eugene Chang 1,25-Dihydroxyvitamin D Decreases Tertiary Butyl-Hydrogen Peroxide-Induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle Cells Molecules adenosine monophosphate-activated protein kinase (ampk) muscle mitochondria oxidative stress sirtuin 1 (sirt1) vitamin d |
| title | 1,25-Dihydroxyvitamin D Decreases Tertiary Butyl-Hydrogen Peroxide-Induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle Cells |
| title_full | 1,25-Dihydroxyvitamin D Decreases Tertiary Butyl-Hydrogen Peroxide-Induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle Cells |
| title_fullStr | 1,25-Dihydroxyvitamin D Decreases Tertiary Butyl-Hydrogen Peroxide-Induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle Cells |
| title_full_unstemmed | 1,25-Dihydroxyvitamin D Decreases Tertiary Butyl-Hydrogen Peroxide-Induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle Cells |
| title_short | 1,25-Dihydroxyvitamin D Decreases Tertiary Butyl-Hydrogen Peroxide-Induced Oxidative Stress and Increases AMPK/SIRT1 Activation in C2C12 Muscle Cells |
| title_sort | 1 25 dihydroxyvitamin d decreases tertiary butyl hydrogen peroxide induced oxidative stress and increases ampk sirt1 activation in c2c12 muscle cells |
| topic | adenosine monophosphate-activated protein kinase (ampk) muscle mitochondria oxidative stress sirtuin 1 (sirt1) vitamin d |
| url | https://www.mdpi.com/1420-3049/24/21/3903 |
| work_keys_str_mv | AT eugenechang 125dihydroxyvitaminddecreasestertiarybutylhydrogenperoxideinducedoxidativestressandincreasesampksirt1activationinc2c12musclecells |