Transcriptional activation of peroxisome proliferator-activated receptor-gamma requires activation of both protein kinase A and Akt during adipocyte differentiation.
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.
Kim
Sang-pil
SP
Department of Thoracic & Cardiovascular Surgery, Pusan National University School of Medicine, Republic of Korea.
Ha
Jung Min
JM
Yun
Sung Ji
SJ
Kim
Eun Kyoung
EK
Chung
Sung Woon
SW
Hong
Ki Whan
KW
Kim
Chi Dae
CD
Bae
Sun Sik
SS
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism / Q000502:physiology*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D017868:Cyclic AMP-Dependent Protein Kinases