Brief Article
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World J Hepatol. Apr 27, 2013; 5(4): 220-225
Published online Apr 27, 2013. doi: 10.4254/wjh.v5.i4.220
PPARγ agonist-induced alterations in Δ6-desaturase and stearoyl-CoA desaturase 1: Role of MEK/ERK1/2 pathway
Negar Saliani, Masoud Darabi, Bahman Yousefi, Behzad Baradaran, Mahmoud Shekari Khaniani, Maryam Darabi, Maghsod Shaaker, Amir Mehdizadeh, Tahereh Naji, Mehrdad Hashemi
Negar Saliani, Masoud Darabi, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 5165665811, Iran
Masoud Darabi, Bahman Yousefi, Maghsod Shaaker, Amir Mehdizadeh, Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Tabriz 5166615731, Iran
Behzad Baradaran, Immunology Research Center, Tabriz University of Medical Sciences, Tabriz 5166615731, Iran
Mahmoud Shekari Khaniani, Department of Medical Genetics, School of Medicine, Tabriz University of Medical Sciences, Tabriz 5166615731, Iran
Maryam Darabi, Maragheh School of Medical Sciences, Tabriz University of Medical Sciences, Tabriz 5516773111, Iran
Tahereh Naji, Department of Biology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran 1941933111, Iran
Mehrdad Hashemi, Department of Genetics, Tehran Medical Branch, Islamic Azad University, Tehran 1916893813, Iran
Author contributions: Darabi M researched literature, conceived the study and wrote manuscript; Saliani N, Yousefi B, Baradaran B, Khaniani MS, Darabi M, Shaaker M, Mehdizadeh A, Naji T and Hashemi M were involved in protocol development and data analysis; all authors reviewed and approved the manuscript.
Supported by A Grant from the Drug Applied Research Center of Tabriz University of Medical Sciences, to Darabi M, Research Projects numbers 89/102 and 90/73
Correspondence to: Masoud Darabi, PhD, Department of Biochemistry and Clinical Laboratories, School of Medicine, Tabriz University of Medical Sciences, Golgasht Avenue, Tabriz 5166615731, Iran. darabim@tbzmed.ac.ir
Telephone: +98-411-3364666 Fax: +98-411-3364666
Received: January 5, 2012
Revised: October 21, 2012
Accepted: October 26, 2012
Published online: April 27, 2013
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Pioglitazone, PD98059, ∆6-desaturase, Stearoyl-CoA desaturase, HepG2 cells