PPARγ agonist-induced alterations in Δ6-desaturase and stearoyl-CoA desaturase 1: Role of MEK/ERK1/2 pathway

AIM: To investigate the effect of MEK/ERK1/2 pathway on peroxisome proliferator-activated receptors (PPAR gamma) agonist-induced alterations in Delta 6-desaturase (Delta 6D) and stearoyl-CoA desaturase 1 (SCD1) in hepatocellular carcinoma cell line HepG2. METHODS: HepG2 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPAR gamma agonist, pioglitazone. Total RNA was isolated and reverse transcribed from treated cells. Changes in gene expression and metabolites ratio, as activity index for Delta 6D and SCD1, were then determined using reverse transcriptionpolymerase chain reaction and gas liquid chromatography, respectively. RESULTS: The expression of both Delta 6D (P = 0.03) and SCD1 (P = 0.01) increased following PD98059 treatment, with a higher impact on SCD1 (24.5% vs 62.5%). Although pioglitazone increased the mRNA level (1.47 +/- 0.10 vs 0.88 +/- 0.02, P = 0.006) and activity index (1.40 +/- 0.07 vs 0.79 +/- 0.11, P < 0.001) of Delta 6D, no such changes have been observed for SCD1 activity index in pioglitazone-treated cells. SCD1 gene expression (+26.4%, P = 0.041) and activity index (+52.8%, P = 0.035) were significantly increased by MEK inhibition in the presence of pioglitazone, as compared with pioglitazone alone and control cells. However, the response of Delta 6D expression and activity index to pioglitazone was unaffected by incubation with PD98059. CONCLUSION: PPAR gamma and ERK1/2 signaling pathway affect differentially and may have inhibitory crosstalk effects on the genes expression of Delta 6D and SCD1, and subsequently on their enzymatic activities. (C) 2013 Baishideng. All rights reserved.