NVS‐HD1 preserves the mitochondria function and increase glucose uptake in C2C12 myoblasts exposed to lipopolysaccharide (LPS)‐induced inflammatory response

Histone deacetylase plays a crucial role in modulating cellular survivals and metabolism. Specific HDAC isoform in the regulation of mitochondria function and glucose hemostasis in lipopolysaccharide (LPS)-induced inflammatory response remains to be determined. We examined the effects of a newly synthesized HDAC4 inhibitor, NVS-HD1 on cell survival and mitochondrial function in differentiated C2C12 cells.C2C12 myoblasts were cultured in DMEM medium until 80% confluency before they were subjected to differentiation medium containing 2% horse serum for 3 consecutive days. C2C12 derived myotubes were then exposed to LPS at the concentration of 10 ng/L for 24 hours. NVS-HD1 (10 nmol/L) and vehicle (Dimethylsulfoxide, DMSO) were treated in differentiated C2C12 cells with or without LPS to define the effect of HDAC4 inhibition on mitochondrial function and glucose uptake.Differentiated C2C12 cells decreased viability in response to LPS stress as evident by and lactate dehydrogenase leakage and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide MTT assay. LPS-induced inflammatory attenuated glucose uptake as comparted to vehicle control. Furthermore, differentiated C2C12 cells displayed an impairment in mitochondrial function by decreasing mitochondrial membrane potential assessed by utilizing the red-fluorescent probe TMRM (tetramethylrhodamine, methyl ester). As compared to DMSO treatment, NVS-HD1 resulted in improvement in cell survival rate and increased glucose uptake, in association with the preservation of mitochondria function in LPS-induced inflammatory response.Our finding is the first demonstration that specific HDAC4 plays a pivotal role in preserving cellular survival, glucose uptake and mitochondrial function in LPS induced inflammatory response.