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

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DOIResolve DOI: http://doi.org/10.1016/j.bbrc.2013.05.068
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TypeArticle
Journal titleBiochemical and Biophysical Research Communications
ISSN0006291X
Volume436
Issue2
Pages169174; # of pages: 6
SubjectRadicicol; Heat shock protein; Differentiation; Adipocytes
AbstractHeat 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 8 days 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.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationNational Research Council Canada; Aquatic and Crop Resource Development
Peer reviewedYes
NRC number55483
NPARC number21268615
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Record identifiere63e9088-3f5e-46ba-91ad-50c882abe7fe
Record created2013-10-28
Record modified2016-05-09
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