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Title: Transcriptional activation of peroxisome proliferator-activated receptor-{gamma} requires activation of both protein kinase A and Akt during adipocyte differentiation

Abstract

Research highlights: {yields} Elevated cAMP activates both PKA and Epac. {yields} PKA activates CREB transcriptional factor and Epac activates PI3K/Akt pathway via Rap1. {yields} Akt modulates PPAR-{gamma} transcriptional activity in concert with CREB. -- Abstract: Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) is required for the conversion of pre-adipocytes. However, the mechanism underlying activation of PPAR-{gamma} is unclear. Here we showed that cAMP-induced activation of protein kinase A (PKA) and Akt is essential for the transcriptional activation of PPAR-{gamma}. Hormonal induction of adipogenesis was blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), by a protein kinase A (PKA) inhibitor (H89), and by a Rap1 inhibitor (GGTI-298). Transcriptional activity of PPAR-{gamma} was markedly enhanced by 3-isobutyl-1-methylxanthine (IBMX), but not insulin and dexamethasone. In addition, IBMX-induced PPAR-{gamma} transcriptional activity was blocked by PI3K/Akt, PKA, or Rap1 inhibitors. 8-(4-Chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT-2'-O-Me-cAMP) which is a specific agonist for exchanger protein directly activated by cAMP (Epac) significantly induced the activation of Akt. Furthermore, knock-down of Akt1 markedly attenuated PPAR-{gamma} transcriptional activity. These results indicate that both PKA and Akt signaling pathways are required for transcriptional activation of PPAR-{gamma}, suggesting post-translational activation of PPAR-{gamma} might be critical step for adipogenic gene expression.

Authors:
 [1]; ; ;  [2];  [1]; ;  [2]
  1. Department of Thoracic and Cardiovascular Surgery, Pusan National University School of Medicine (Korea, Republic of)
  2. MRC for Ischemic Tissue Regeneration, Medical Research Institute, and Department of Pharmacology, Pusan National University School of Medicine (Korea, Republic of)
Publication Date:
OSTI Identifier:
22202733
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 399; Journal Issue: 1; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMP; DEXAMETHASONE; GENES; INDUCTION; INSULIN; RECEPTORS

Citation Formats

Kim, Sang-pil, Ha, Jung Min, Yun, Sung Ji, Kim, Eun Kyoung, Chung, Sung Woon, Hong, Ki Whan, Kim, Chi Dae, and Bae, Sun Sik, E-mail: sunsik@pusan.ac.kr. Transcriptional activation of peroxisome proliferator-activated receptor-{gamma} requires activation of both protein kinase A and Akt during adipocyte differentiation. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.07.038.
Kim, Sang-pil, Ha, Jung Min, Yun, Sung Ji, Kim, Eun Kyoung, Chung, Sung Woon, Hong, Ki Whan, Kim, Chi Dae, & Bae, Sun Sik, E-mail: sunsik@pusan.ac.kr. Transcriptional activation of peroxisome proliferator-activated receptor-{gamma} requires activation of both protein kinase A and Akt during adipocyte differentiation. United States. https://doi.org/10.1016/J.BBRC.2010.07.038
Kim, Sang-pil, Ha, Jung Min, Yun, Sung Ji, Kim, Eun Kyoung, Chung, Sung Woon, Hong, Ki Whan, Kim, Chi Dae, and Bae, Sun Sik, E-mail: sunsik@pusan.ac.kr. 2010. "Transcriptional activation of peroxisome proliferator-activated receptor-{gamma} requires activation of both protein kinase A and Akt during adipocyte differentiation". United States. https://doi.org/10.1016/J.BBRC.2010.07.038.
@article{osti_22202733,
title = {Transcriptional activation of peroxisome proliferator-activated receptor-{gamma} requires activation of both protein kinase A and Akt during adipocyte differentiation},
author = {Kim, Sang-pil and Ha, Jung Min and Yun, Sung Ji and Kim, Eun Kyoung and Chung, Sung Woon and Hong, Ki Whan and Kim, Chi Dae and Bae, Sun Sik, E-mail: sunsik@pusan.ac.kr},
abstractNote = {Research highlights: {yields} Elevated cAMP activates both PKA and Epac. {yields} PKA activates CREB transcriptional factor and Epac activates PI3K/Akt pathway via Rap1. {yields} Akt modulates PPAR-{gamma} transcriptional activity in concert with CREB. -- Abstract: Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) is required for the conversion of pre-adipocytes. However, the mechanism underlying activation of PPAR-{gamma} is unclear. Here we showed that cAMP-induced activation of protein kinase A (PKA) and Akt is essential for the transcriptional activation of PPAR-{gamma}. Hormonal induction of adipogenesis was blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002), by a protein kinase A (PKA) inhibitor (H89), and by a Rap1 inhibitor (GGTI-298). Transcriptional activity of PPAR-{gamma} was markedly enhanced by 3-isobutyl-1-methylxanthine (IBMX), but not insulin and dexamethasone. In addition, IBMX-induced PPAR-{gamma} transcriptional activity was blocked by PI3K/Akt, PKA, or Rap1 inhibitors. 8-(4-Chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT-2'-O-Me-cAMP) which is a specific agonist for exchanger protein directly activated by cAMP (Epac) significantly induced the activation of Akt. Furthermore, knock-down of Akt1 markedly attenuated PPAR-{gamma} transcriptional activity. These results indicate that both PKA and Akt signaling pathways are required for transcriptional activation of PPAR-{gamma}, suggesting post-translational activation of PPAR-{gamma} might be critical step for adipogenic gene expression.},
doi = {10.1016/J.BBRC.2010.07.038},
url = {https://www.osti.gov/biblio/22202733}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 399,
place = {United States},
year = {Fri Aug 13 00:00:00 EDT 2010},
month = {Fri Aug 13 00:00:00 EDT 2010}
}