Effects of 5-aminoimidazole-4-carboxamide ribonucleotide on the palmitic acid-induced expression of mitochondrial function-related proteins in C2 C12 skeletal muscle cells

Abstract

Objective To investigate the effects of activated protein kinase(AMPK)agonists on the expression of peroxisome proliferator-activated receptor γ coactivator 1α(PGC1α), 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. Key words: Adenylate kinase; Mitochondria; Muscle, skeletal