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.
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.
Authors: Yun Wang; Daniela Botolin; Jinghua Xu; Barbara Christian; Ernestine Mitchell; Bolleddula Jayaprakasam; Muraleedharan G Nair; Muraleedharan Nair; Jeffrey M Peters; Jeffery M Peters; Julia V Busik; Julia Busik; L Karl Olson; Donald B Jump Journal: J Lipid Res Date: 2006-06-21 Impact factor: 5.922
Authors: Barbara D Pachikian; Ahmed Essaghir; Jean-Baptiste Demoulin; Audrey M Neyrinck; Emilie Catry; Fabienne C De Backer; Nicolas Dejeans; Evelyne M Dewulf; Florence M Sohet; Laurence Portois; Louise Deldicque; Olivier Molendi-Coste; Isabelle A Leclercq; Marc Francaux; Yvon A Carpentier; Fabienne Foufelle; Giulio G Muccioli; Patrice D Cani; Nathalie M Delzenne Journal: PLoS One Date: 2011-08-10 Impact factor: 3.240
Authors: Renée Deehan; Pia Maerz-Weiss; Natalie L Catlett; Guido Steiner; Ben Wong; Matthew B Wright; Gil Blander; Keith O Elliston; William Ladd; Maria Bobadilla; Jacques Mizrahi; Carolina Haefliger; Alan Edgar Journal: PLoS One Date: 2012-04-13 Impact factor: 3.240