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 (CoCl2)-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 CoCl2 induced cytotoxicity. Molecular markers of hypoxia, induced by CoCl2, were normalized or reduced by MSM, which also inhibited the effect of CoCl2-induced JAK2/STAT5b/Cyclin D1 and PI3K/AKT signaling. CoCl2-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.
Keywords: CoCl(2); Hypoxia; JAK2/STAT5b/Cyclin D1; MSM; NRF2/HO-1; PI3K/AKT.
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