Cholecalciferol (vitamin D3) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes

Teixeira, Maraiza Alves; Feudis, Marilisa De; Reano, Simone; Raiteri, Tommaso; Scircoli, Andrea; Zaggia, Ivan; Ruga, Sara; Salvadori, Laura; Prodam, Flavia; Marzullo, Paolo; Molinari, Claudio; Corà, Davide; Filigheddu, Nicoletta

doi:10.18632/aging.202669

Cited by 9 publications

(13 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The contrasting conclusions of our work compared with those of previously published studies probably depend, in large part, on differences in the methodologies or cells used. Indeed, the majority of the works reporting positive activity of 1,25VD on mitochondria were performed on undifferentiated myoblasts [ 13 , 16 ], while our data, as well as previously published data demonstrating the atrophic activity of 1,25VD [ 18 ], were obtained on differentiated myotubes, a cellular model which is closer than myoblasts to adult muscle fibers [ 19 ]. Indeed, the content, network shape, and function of mitochondria dramatically change with differentiation from myoblasts to myotubes [ 37 ].…”

Section: Discussionsupporting

confidence: 81%

“…As the effects of 1,25VD on mitochondria and myotube diameters are divergent from those of VD3 and 25VD ( Figure 1 , Figure 2 and Figure 3 and [ 18 , 19 ]), we assessed the effect of these metabolites on ROS production in C2C12 myotubes. We observed that 1,25VD caused a significant increase of fluorescence in CellROX-loaded cells, while both VD3 and 25VD lowered the basal levels ( Figure 6 a,b), suggesting that 1,25VD might induce oxidative stress in C2C12 myotubes, whereas VD3 and 25VD might act as antioxidants.…”

Section: Resultsmentioning

confidence: 99%

“…Accordingly, when analyzing the OCR in myoblasts treated with 1,25VD, we found a moderate increase in the maximal mitochondrial respiration (data not shown), in accordance with previously reported findings [ 13 ]. In addition to the basal different content and activity of mitochondria in myoblasts vs. myotubes, we reported, upon 1,25VD treatment, an apparent lack of VDR-RXR nuclear translocation in myotubes compared to myoblasts [ 19 ]. Since proper VDR function is required for 1,25VD effects on myoblasts mitochondrial activity [ 15 ], this could be a further mechanism underlying the differences in the effects of 1,25VD on myotubes compared to myoblasts.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the effects of 1,25VD upstream metabolites VD3 and 25VD on mitochondria are less straightforward. As both VD3 and 25VD own a protective activity on C2C12 myotubes in the presence of atrophic stimuli [ 18 , 19 ], it is possible to envision that more striking effects on mitochondrial metabolism could be detected in an atrophic context. The differences between VD3 and 25VD in some assays ( Figure 1 b and Figure 2 b,c) may point to the fact that VD3 is not converted to 25VD in C2C12 myotubes, and that it probably acts through different mechanisms [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, despite the evidence correlating vitamin D deficiency with muscular impairment and the undisputed importance of the VD/VDR system for skeletal muscle health, treatment of C2C12 myotubes with 1,25VD negatively impinges on myotube size [ 11 , 18 ]. In contrast, the upstream metabolites of 1,25VD, namely VD3 and 25VD, have an anti-atrophic activity on the same in vitro cellular model [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

The Atrophic Effect of 1,25(OH)2 Vitamin D3 (Calcitriol) on C2C12 Myotubes Depends on Oxidative Stress

et al. 2021

Self Cite

View full text Add to dashboard Cite

Dysfunctional mitochondrial metabolism has been linked to skeletal muscle loss in several physio-pathological states. Although it has been reported that vitamin D (VD) supports cellular redox homeostasis by maintaining normal mitochondrial functions, and VD deficiency often occurs in conditions associated with skeletal muscle loss, the efficacy of VD supplementation to overcome muscle wasting is debated. Investigations on the direct effects of VD metabolites on skeletal muscle using C2C12 myotubes have revealed an unexpected pro-atrophic activity of calcitriol (1,25VD), while its upstream metabolites cholecalciferol (VD3) and calcidiol (25VD) have anti-atrophic effects. Here, we investigated if the atrophic effects of 1,25VD on myotubes depend on its activity on mitochondrial metabolism. The impact of 1,25VD and its upstream metabolites VD3 and 25VD on mitochondria dynamics and the activity of C2C12 myotubes was evaluated by measuring mitochondrial content, architecture, metabolism, and reactive oxygen species (ROS) production. We found that 1,25VD induces atrophy through protein kinase C (PKC)-mediated ROS production, mainly of extramitochondrial origin. Consistent with this, cotreatment with the antioxidant N-acetylcysteine (NAC), but not with the mitochondria-specific antioxidant mitoTEMPO, was sufficient to blunt the atrophic activity of 1,25VD. In contrast, VD3 and 25VD have antioxidant properties, suggesting that the efficacy of VD supplementation might result from the balance between atrophic pro-oxidant (1,25VD) and protective antioxidant (VD3 and 25VD) metabolites.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The Atrophic Effect of 1,25(OH)2 Vitamin D3 (Calcitriol) on C2C12 Myotubes Depends on Oxidative Stress

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

Maternal vitamin D deficiency affects the morphology and function of glycolytic muscle in adult offspring rats

Reis

Assis

Lautherbach

et al. 2022

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Fetal stage is a critical developmental window for the skeletal muscle, but little information is available about the impact of maternal vitamin D (Vit. D) deficiency (VDD) on offspring lean mass development in the adult life of male and female animals. Methods Female rats (Wistar Hannover) were fed either a control (1000 IU Vit. D3/kg) or a VDD diet (0 IU Vit. D3/kg) for 6 weeks and during gestation and lactation. At weaning, male and female offspring were randomly separated and received a standard diet up to 180 days old. Results Vitamin D deficiency induced muscle atrophy in the male (M-VDD) offspring at the end of weaning, an effect that was reverted along the time. Following 180 days, fast-twitch skeletal muscles [extensor digitorum longus (EDL)] from the M-VDD showed a decrease (20%; P < 0.05) in the number of total fibres but an increase in the cross-sectional area of IIB (17%; P < 0.05), IIA (19%; P < 0.05) and IIAX (21%; P < 0.05) fibres. The fibre hypertrophy was associated with the higher protein levels of MyoD (73%; P < 0.05) and myogenin (55% %; P < 0.05) and in the number of satellite cells (128.8 ± 14 vs. 91 ± 7.6 nuclei Pax7 + in the M-CTRL; P < 0.05). M-VDD increased time to fatigue during ex vivo contractions of EDL muscles and showed an increase in the phosphorylation levels of IGF-1/ insulin receptor and their downstream targets related to anabolic processes and myogenic activation, including Ser 473 Akt and Ser 21/9 GSK-3β. In such muscles, maternal VDD induced a compensatory increase in the content of calcitriol (two-fold; P < 0.05) and CYP27B1 (58%; P < 0.05), a metabolizing enzyme that converts calcidiol to calcitriol. Interestingly, most morphological and biochemical changes found in EDL were not observed in slow-twitch skeletal muscles (soleus) from the M-VDD group as well as in both EDL and soleus muscles from the female offspring. Conclusions These data show that maternal VDD selectively affects the development of type-II muscle fibres in male offspring rats but not in female offspring rats and suggest that the enhancement of their size and fatigue resistance in fast-twitch skeletal muscle (EDL) is probably due to a compensatory increase in the muscle content of Vit. D in the adult age.

show abstract

Vitamin D and skeletal muscle

Girgis

2024

Feldman and Pike' S Vitamin D

View full text Add to dashboard Cite

Cholecalciferol (vitamin D3) has a direct protective activity against interleukin 6-induced atrophy in C2C12 myotubes

Cited by 9 publications

References 47 publications

The Atrophic Effect of 1,25(OH)2 Vitamin D3 (Calcitriol) on C2C12 Myotubes Depends on Oxidative Stress

The Atrophic Effect of 1,25(OH)2 Vitamin D3 (Calcitriol) on C2C12 Myotubes Depends on Oxidative Stress

Maternal vitamin D deficiency affects the morphology and function of glycolytic muscle in adult offspring rats

Vitamin D and skeletal muscle

Contact Info

Product

Resources

About