Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells

PPAR Research
Rehana ParvinA Sugawara

Abstract

Although therapeutic effects of the peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists rosiglitazone and pioglitazone against Cushing's disease have been reported, their effects are still controversial and inconsistent. We therefore examined the effects of a novel PPAR-γ agonist, MEKT1, on Pomc expression/ACTH secretion using murine corticotroph-derived AtT20 cells and compared its effects with those of rosiglitazone and pioglitazone. AtT20 cells were treated with either 1 nM~10 μM MEKT1, rosiglitazone, or pioglitazone for 24 hours. Thereafter, their effects on proopiomelanocortin gene (Pomc) mRNA expression were studied by qPCR and the Pomc promoter (-703/+58) activity was demonstrated by luciferase assay. Pomc mRNA expression and promoter activity were significantly inhibited by MEKT1 at 10 μM compared to rosiglitazone and pioglitazone. SiRNA-mediated PPAR-γ knockdown significantly abrogated MEKT1-mediated Pomc mRNA suppression. ACTH secretion from AtT20 cells was also significantly inhibited by MEKT1. Deletion/point mutant analyses of Pomc promoter indicated that the MEKT1-mediated suppression was mediated via NurRE, TpitRE, and NBRE at -404/-383, -316/-309, and -69/-63, respectively. Moreover, MEKT1 signific...Continue Reading

References

Nov 1, 1987·Molecular and Cellular Biology·L JeannotteJ Drouin
Oct 7, 1997·Molecular and Cellular Biology·A PhilipsJ Drouin
Oct 29, 1997·Molecular and Cellular Biology·G PoulinJ Drouin
Jan 9, 2004·The Journal of Biological Chemistry·Katia P KaralisChristina Chandras
Apr 2, 2004·Nature Medicine·Ronald M EvansYong-Xu Wang
Aug 7, 2004·European Journal of Endocrinology·Bruno AmbrosiPaolo Beck-Peccoz
Dec 9, 2004·The Journal of Clinical Endocrinology and Metabolism·Daesman Suri, Roy E Weiss
Jan 18, 2006·Pituitary·Anthony P Heaney
Jan 20, 2006·Journal of Endocrinological Investigation·F BogazziE Martino
Jan 25, 2006·Clinical Endocrinology·Francesca Pecori GiraldiFrancesco Cavagnini
Jul 11, 2006·FEBS Letters·Akihiro YamashitaRyuzo Torii
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Ramya KapadiaRaghu Vemuganti
Jul 8, 2008·Journal of Neuroendocrinology·A B Bicknell
Sep 21, 2010·Neuroendocrinology·Massimo MannelliMichaela Luconi
Nov 30, 2011·Current Molecular Pharmacology·Akira SugawaraSadayoshi Ito
Jan 17, 2012·Journal of Advanced Pharmaceutical Technology & Research·Sandeep TyagiSaurabh Sharma
Jun 8, 2012·Pituitary·Maria Fleseriu, Stephan Petersenn
Feb 5, 2016·Current Medicinal Chemistry·Silvia Martina FerrariPoupak Fallahi
Oct 5, 2017·Cellular and Molecular Neurobiology·Sonia Villapol
Nov 23, 2017·Diabetology & Metabolic Syndrome·Elena FilipovaToni Vekov

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Citations

Oct 28, 2019·Reviews in Endocrine & Metabolic Disorders·Syeda Momna IshtiaqJunaid Ali Khan

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Methods Mentioned

BETA
PCR
Assay
Immunoprecipitation
DNA Extraction
ChIP

Software Mentioned

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