Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc ExpressionACTH Secretion in AtT20 Cells
Joint Authors
Sugawara, Akira
Yokoyama, Atsushi
Parvin, Rehana
Noro, Erika
Saito-Hakoda, Akiko
Shimada, Hiroki
Suzuki, Susumu
Shimizu, Kyoko
Miyachi, Hiroyuki
Source
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-04-23
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Abstract EN
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 significantly suppressed Nur77, Nurr1, and Tpit mRNA expression.
MEKT1 also was demonstrated to inhibit the protein-DNA interaction of Nur77/Nurr1-NurRE, Tpit-TpitRE, and Nur77-NBRE by ChIP assay.
Taken together, it is suggested that MEKT1 could be a novel therapeutic medication for Cushing’s disease.
American Psychological Association (APA)
Parvin, Rehana& Noro, Erika& Saito-Hakoda, Akiko& Shimada, Hiroki& Suzuki, Susumu& Shimizu, Kyoko…[et al.]. 2018. Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc ExpressionACTH Secretion in AtT20 Cells. PPAR Research،Vol. 2018, no. 2018, pp.1-16.
https://search.emarefa.net/detail/BIM-1212519
Modern Language Association (MLA)
Parvin, Rehana…[et al.]. Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc ExpressionACTH Secretion in AtT20 Cells. PPAR Research No. 2018 (2018), pp.1-16.
https://search.emarefa.net/detail/BIM-1212519
American Medical Association (AMA)
Parvin, Rehana& Noro, Erika& Saito-Hakoda, Akiko& Shimada, Hiroki& Suzuki, Susumu& Shimizu, Kyoko…[et al.]. Inhibitory Effects of a Novel PPAR-γ Agonist MEKT1 on Pomc ExpressionACTH Secretion in AtT20 Cells. PPAR Research. 2018. Vol. 2018, no. 2018, pp.1-16.
https://search.emarefa.net/detail/BIM-1212519
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1212519