Methylsulfonylmethane relieves cobalt chloride-induced hypoxic toxicity in C2C12 myoblasts.

Aims: In biology and medicine, hypoxia refers to reduced oxygen tension or oxygen starvation resulting from various environmental or pathological conditions. Prolonged hypoxia may lead to an imbalance in protein production and a loss of muscle mass in animals. The physiological response to hypoxia includes oxidative stress-induced activation of complex cell-signaling networks such as hypoxia-inducible factor (HIF), phosphoinositide 3-kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK-STAT). Methylsulfonylmethane (MSM) is a natural sulfur compound that regulates HIF-1α expression and provides cytoprotection from oxidative stress. In this study, we explored the anti-hypoxic activity and cytoprotective effect of MSM in cobalt chloride (CoCl)-induced hypoxic C2C12 mouse myoblast culture.

Materials And Methods: We used western blotting, real time PCR, flow cytometry for molecular signaling studies and we also used MTT assay and ChIP assay along with comet assay for cellular processes.

Key Findings: MSM prevented the CoCl induced cytotoxicity. Molecular markers of hypoxia, induced by CoCl, were normalized or reduced by MSM, which also inhibited the effect of CoCl-induced JAK2/STAT5b/Cyclin D1 and PI3K/AKT signaling. CoCl-induced oxidative stress results in activation of the NRF2/HO-1-mediated cell survival pathway and inhibition of DNA repair, both of which were prevented by MSM.

Significance: We suggest MSM can be considered as a candidate drug for reducing the effects of hypoxia in both animals and humans.