Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes.

Abstract

Heat shock protein 90 (Hsp90) is involved in various cellular processes, such as cell proliferation, differentiation and apoptosis. As adipocyte differentiation plays a critical role in obesity development, the present study investigated the effect of an Hsp90 inhibitor radicicol on the differentiation of 3T3-L1 preadipocytes and potential mechanisms. The cells were treated with different concentrations of radicicol during the first 8days of cell differentiation. Adipogenesis, the expression of adipogenic transcriptional factors, differentiation makers and cell cycle were determined. It was found that radicicol dose-dependently decreased intracellular fat accumulation through down-regulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT element binding protein α (C/EBPα), fatty acid synthase (FAS) and fatty acid-binding protein 4 (FABP4). Flow cytometry analysis revealed that radicicol blocked cell cycle at G1-S phase. Radicicol redcued the phosphorylation of Akt while showing no effect on β-catenin expression. Radicicol decreased the phosphorylation of phosphoinositide-dependent kinase 1 (PDK1). The results suggest that radicicol inhibited 3T3-L1 preadipocyte differentiation through affecting the PDK1/Akt pathway and subsequent inhibition of mitotic clonal expansion and the expression/activity of adipogenic transcriptional factors and their downstream adipogenic proteins.

• Authors: Yonghan He, Ying Li, Shuocheng Zhang, Ben Perry, Tiantian Zhao, Yanwen Wang, Changhao Sun
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 436 Issue 2 Pg. 169-74 (Jun 28 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23727383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• CCAAT-Enhancer-Binding Proteins
• CEBPA protein, mouse
• Fabp4 protein, mouse
• Fats
• Fatty Acid-Binding Proteins
• HSP90 Heat-Shock Proteins
• Macrolides
• PPAR gamma
• Pdk1 protein, mouse
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• Fatty Acid Synthases
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• monorden

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, drug effects, metabolism)
• Adipogenesis (drug effects)
• Animals
• Blotting, Western
• CCAAT-Enhancer-Binding Proteins (metabolism)
• Cell Differentiation (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Fats (metabolism)
• Fatty Acid Synthases (metabolism)
• Fatty Acid-Binding Proteins (metabolism)
• Flow Cytometry
• G1 Phase Cell Cycle Checkpoints (drug effects)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors, metabolism)
• Macrolides (pharmacology)
• Mice
• PPAR gamma (metabolism)
• Phosphorylation (drug effects)
• Protein Serine-Threonine Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyruvate Dehydrogenase Acetyl-Transferring Kinase
• Signal Transduction (drug effects)