Effects of 5-aminoimidazole-4-carboxamide ribonucleotide on the palmitic acid-induced expression of mitochondrial function-related proteins in C2 C12 skeletal muscle cells / 中华老年医学杂志

ABSTRACT

Objective To investigate the effects of activated protein kinase(AMPK)agonists on the expression of peroxisome proliferator-activated receptor γ coactivator 1α(PGC1a),mitofusin 2 (Mfn2) and nuclear respiratory factor1 (NRF1)in the process of lipid-induced mitochondrial dysfunction of skeletal muscles.Methods The expression of PGC1α,Mfn2 and NRF1 in C2C12 skeletal muscle cells after intervention with palmitic acid was detected using reverse transcription-polymerase chain reaction(RT-PCR)and Western blotting.The effect of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on Mfn2 and NRF1 and,the expression of Mfn2 and NRF1 in C2C12 cells induced by a PGC1α activator and PGC1α-siRNA were assessed by Western blotting.Results Palmitic acid decreased the mRNA and protein expression of PGC1α,Mfn2 and NRF1 in C2C12 cells (P＜0.05).Additionally,AICAR,rosiglitazone and metformin up-regulated PGC1α expression,regardless of the presence of palmitic acid and,AICAR reversed lipid-induced PGC1α,Mfn2 and NRF1 attenuation in C2C12 cells.Furthermore,Mfn2 and NRF1 protein expression increased with PGC1α over-expression,and decreased with down-regulated PGC1α expression.Conclusions AICAR can relieve the adverse effects of palmitic acid on PGC1α,Mfn2 and NRF1 in skeletal muscle cells.Moreover,it appears that AICAR can up-regulate Mfn2 and NRF1 expression through activating PGC1α.