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:
-
- Department of Thoracic and Cardiovascular Surgery, Pusan National University School of Medicine (Korea, Republic of)
- 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}
}