Bahman Yousefi
1, Masoud Darabi
2,3*, Behzad Baradaran
4, Mahmoud Shekari Khaniani
5, Mohammad Rahbani
2, Maryam Darabi
6, Shabnam Fayezi
1, Amir Mehdizadeh
2, Negar Saliani
2, Maghsod Shaaker
21 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3 Students’ Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
4 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
5 Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
6 Department of Biochemistry and Genetics, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
Abstract
Introduction:
The extracellular signal-regulated kinase (ERK) mitogen-activated
protein kinase pathway, also known as the MEK/ERK1/2 kinase cascade, has
recently been implicated in the regulation of lipid metabolism and
fatty liver disease. However, its functional effect on cellular fatty
acid composition is unknown. Herein, we examined the effect of a
pharmacological inhibitor of MEK, the upstream kinase activator of
ERK1/2, on fatty acid composition of hepatocellular carcinoma cell line
HepG2. Methods: HepG2 cells cultured in
RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor
PD98059 and were investigated with respect to fatty acid composition by
gas-liquid chromatography. Results: Exposure
of cells to the ERK1/2 pathway inhibitor induced an increase in
monounsaturated fatty acids and the fatty acid desaturation index and a
decrease in polyunsaturated fatty acid content. Specifically, we showed a
significant increase of oleic acid (18:1n‑9; +29%, P=0.003) and
arachidonic acid (20:4n‑6)/linoleic acid (18:2n‑6) ratio (3.5-fold;
P<0.001) in HepG2 cells. Conclusion:
Cellular fatty acid composition of HepG2 cells appeared to be
differentially regulated by ERK1/2 pathway, thus suggesting related
metabolic pathways as potential mediators of the effects of ERK1/2
signaling on hepatic fatty acid composition.