Vitamin D treatment protects against and reverses oxidative stress induced muscle proteolysis

• In vivo vitamin D deficiency leads to mild oxidative and nitrosative stress in muscle.
• Absence of vitamin D leads to decreased SOD activity both in vivo and in vitro.
• Pre-treatment with vitamin D has a protective effect on oxidative stress induced muscle proteolysis in C2C12 cells.
• Vitamin D treatment reverses the adverse effects of oxidative stress on muscle proteolysis in C2C12 cells.

Vitamin D is known to have a biological role in many extra skeletal tissues in the body including muscle. Vitamin D deficiency has been associated with preferential atrophy of type II fibres in human muscle. Vitamin D at physiological concentrations is known to protect cells against oxidative damage. In this study we examined whether vitamin D deficiency induces muscle oxidative stress in a rat model and further if pre or post treatment of C2C12 muscle cells with vitamin D offers protection against oxidative stress induced muscle proteolysis. Protein carbonylation as a marker of protein oxidation was increased in both the deficient muscle and vehicle-treated C2C12 cells. Vitamin D deficiency led to an increase in activities of the glutathione-dependent enzymes and decrease in SOD and catalase enzymes in the rat muscle. Higher nitrate levels indicative of nitrosative stress were observed in the deficient muscle compared to control muscle. Rehabilitation with vitamin D could reverse the alterations in oxidative and nitrosative stress parameters. Increase in total protein degradation, 20S proteasomal enzyme activity, muscle atrophy gene markers and expression of proteasome subunit genes induced by oxidative stress were corrected both by pre/post treatment of C2C12 muscle cells with vitamin D. Increase in SOD activity in the presence of vitamin D indicates antioxidant potential of vitamin D in the muscle. The data presented indicates that vitamin D deficiency leads to mild oxidative stress in the muscle which may act as a trigger for increased proteolysis in the vitamin D deficient muscle.