scholarly journals Vitamin D Attenuates FOXO1-Target Atrophy Gene Expression in C2C12 Muscle Cells

2018 ◽  
Vol 64 (3) ◽  
pp. 229-232 ◽  
Author(s):  
Yuma HIROSE ◽  
Takumi ONISHI ◽  
Shinji MIURA ◽  
Yukino HATAZAWA ◽  
Yasutomi KAMEI
Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2806 ◽  
Author(s):  
Eugene Chang ◽  
Yangha Kim

Excessive fat accumulation has been considered as a major contributing factor for muscle mitochondrial dysfunction and its associated metabolic complications. The purpose of present study is to investigate a role of vitamin D in muscle fat accumulation and mitochondrial changes. In differentiated C2C12 muscle cells, palmitic acid (PA) was pretreated, followed by incubation with 1,25-dihyroxyvitamin D (1,25(OH)2D) for 24 h. PA led to a significant increment of triglyceride (TG) levels with increased lipid peroxidation and cellular damage, which were reversed by 1,25(OH)2D. The supplementation of 1,25(OH)2D significantly enhanced PA-decreased mtDNA levels as well as mRNA levels involved in mitochondrial biogenesis such as nuclear respiratory factor 1 (NRF1), peroxisome proliferative activated receptor gamma coactivator-1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in C2C12 myotubes. Additionally, 1,25(OH)2D significantly increased ATP levels and gene expression related to mitochondrial function such as carnitine palmitoyltransferase 1 (CPT1), peroxisome proliferator-activated receptor α (PPARα), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD), medium-chain acyl-CoA dehydrogenase (MCAD), uncoupling protein 2 (UCP2), and UCP3 and the vitamin D pathway including 25-dihydroxyvitamin D3 24-hydroxylase (CYP24) and 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27) in PA-treated C2C12 myotubes. In addition to significant increment of sirtuin 1 (SIRT1) mRNA expression, increased activation of adenosine monophosphate-activated protein kinase (AMPK) and SIRT1 was found in 1,25(OH)2D-treated C2C12 muscle cells. Thus, we suggest that the observed protective effect of vitamin D on muscle fat accumulation and mitochondrial dysfunction in a positive manner via modulating AMPK/SIRT1 activation.


2010 ◽  
Vol 42 ◽  
pp. 94
Author(s):  
Kevin S. O'Fallon ◽  
Priscilla M. Clarkson ◽  
Lawrence M. Schwartz

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3903 ◽  
Author(s):  
Chang

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.


2007 ◽  
Vol 293 (5) ◽  
pp. F1592-F1604 ◽  
Author(s):  
J. Ruth Wu-Wong ◽  
Masaki Nakane ◽  
Junli Ma ◽  
Xiaoan Ruan ◽  
Paul E. Kroeger

Clinical observations show that an increase in serum inorganic phosphorus (Pi) is linked to higher cardiovascular (CV) mortality, while vitamin D receptor (VDR) agonist therapy is associated with survival benefit in stage 5 chronic kidney disease. Smooth muscle cells (SMCs) play an important role in CV pathophysiology, but the interaction between Pi and the VDR signaling pathway in SMCs is not known. Real-time RT-PCR studies revealed that elevated Pi (2.06 mM) modulated VDR-mediated regulation of a panel of genes including thrombomodulin and osteopontin in SMCs. DNA microarray results demonstrated that increasing Pi from 0.9 to 2.06 mM exerted a widespread modulating effect on VDR-mediated gene expression. A total of 325 target genes were affected by paricalcitol at 0.9 mM Pi, with 195 up- and 130 downregulated. The number of target genes affected by paricalcitol at 2.06 mM Pi decreased to 86, with 55 up- and 31 downregulated. VDR-mediated gene expression in As4.1 cells (a juxtaglomerular cell-like cell line derived from kidney tumors in SV40 T-antigen transgenic mice) and peroxisome proliferator-activated receptor (PPAR)γ-mediated gene expression in SMCs were also altered by elevated Pi, suggesting that the observation is not unique to VDR in SMCs. Mechanism analysis showed that elevated Pi had no significant effect on VDR or PPARγ protein level but altered the cytosolic vs. nuclear distribution of NF-κB or nuclear receptor corepressor 1 (NCoR1). Our results demonstrate for the first time that elevated Pi affects VDR-mediated gene expression in human coronary artery SMCs and the effect is not limited to VDR in SMCs.


2020 ◽  
Vol 319 (2) ◽  
pp. G253-G260
Author(s):  
Carmen J. Reynolds ◽  
Nicholas J. Koszewski ◽  
Ronald L. Horst ◽  
Donald C. Beitz ◽  
Jesse P. Goff

We found that 25OHD-Gluc, an endogenously produced metabolite, is delivered to the colon via bile to induce vitamin D-mediated responses in the colon.


Circulation ◽  
2000 ◽  
Vol 102 (15) ◽  
pp. 1828-1833 ◽  
Author(s):  
Georg Nickenig ◽  
Kerstin Strehlow ◽  
Sven Wassmann ◽  
Anselm T. Bäumer ◽  
Katja Albory ◽  
...  

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