title: PPARγ agonist-induced alterations in Δ6-desaturase and stearoyl-CoA desaturase 1: Role of MEK/ERK1/2 pathway.
abstract: OBJECTIVE
  To investigate the effect of MEK/ERK1/2 pathway on peroxisome proliferator-activated receptors (PPARγ) agonist-induced alterations in Δ6-desaturase (Δ6D) 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 PPARγ agonist, pioglitazone. Total RNA was isolated and reverse transcribed from treated cells. Changes in gene expression and metabolites ratio, as activity index for Δ6D and SCD1, were then determined using reverse transcription-polymerase chain reaction and gas liquid chromatography, respectively.
  
  
  RESULTS
  The expression of both Δ6D (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 Δ6D, 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 Δ6D expression and activity index to pioglitazone was unaffected by incubation with PD98059.
  
  
  CONCLUSIONS
  PPARγ and ERK1/2 signaling pathway affect differentially and may have inhibitory crosstalk effects on the genes expression of ∆6D and SCD1, and subsequently on their enzymatic activities.
authors.affiliation: Negar Saliani, Masoud Darabi, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran.
authors.forename: Negar
authors.initials: N
authors.lastname: Saliani
authors.forename: Masoud
authors.initials: M
authors.lastname: Darabi
authors.forename: Bahman
authors.initials: B
authors.lastname: Yousefi
authors.forename: Behzad
authors.initials: B
authors.lastname: Baradaran
authors.forename: Mahmoud Shekari
authors.initials: MS
authors.lastname: Khaniani
authors.forename: Maryam
authors.initials: M
authors.lastname: Darabi
authors.forename: Maghsod
authors.initials: M
authors.lastname: Shaaker
authors.forename: Amir
authors.initials: A
authors.lastname: Mehdizadeh
authors.forename: Tahereh
authors.initials: T
authors.lastname: Naji
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hashemi
keywords: HepG2 cells; PD98059; Pioglitazone; Stearoyl-CoA desaturase; ∆6-desaturase