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

He, Yonghan; Li, Ying; Zhang, Shuocheng; Perry, Ben; Zhao, Tiantian; Wang, Yanwen; Sun, Changhao

doi:10.1016/J.BBRC.2013.05.068

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

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Abstract

Highlights: •Radicicol suppressed intracellular fat accumulation in 3T3-L1 adipocytes. •Radicicol inhibited the expression of FAS and FABP4. •Radicicol blocked cell cycle at the G1-S phase during cell differentiation. •Radicicol inhibited the PDK1/Akt pathway in adipocyte differentiation. -- 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 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 (PPAR{sub γ}) and CCAAT element binding protein α (C/EBP{sub α}), 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 throughmore »« less

Authors:

He, Yonghan ^[1]; Li, Ying ^[1]; Zhang, Shuocheng ^[2]; Perry, Ben ^[2]; Zhao, Tiantian ^[2]; Wang, Yanwen ^[2]; Sun, Changhao ^[1]

Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Harbin 150081 (China)
Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 (Canada)

Publication Date:: Fri Jun 28 00:00:00 EDT 2013

OSTI Identifier:: 22239640

Resource Type:: Journal Article

Journal Name:: Biochemical and Biophysical Research Communications

Additional Journal Information:: Journal Volume: 436; Journal Issue: 2; Other Information: Copyright (c) 2013 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; APOPTOSIS; CALVES; CARBOXYLIC ACIDS; CELL CYCLE; CELL DIFFERENTIATION; CELL PROLIFERATION; CONCENTRATION RATIO; ELECTROPHORESIS; FATS; FLUORESCENCE; GELS; HEAT-SHOCK PROTEINS; INHIBITION; METABOLIC DISEASES; PHOSPHORYLATION; RECEPTORS; RNA-ASE

Citation Formats


                    He, Yonghan, Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Li, Ying, Zhang, Shuocheng, Perry, Ben, Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3, Zhao, Tiantian, Department of Psychology, University of Toronto, 1265 Military Trail, Toronto, ON, Canada M1C 1A4, Wang, Yanwen, Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3, and Sun, Changhao. Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes.  United States: N. p., 2013. 
        Web.  doi:10.1016/J.BBRC.2013.05.068.

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                    He, Yonghan, Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Li, Ying, Zhang, Shuocheng, Perry, Ben, Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3, Zhao, Tiantian, Department of Psychology, University of Toronto, 1265 Military Trail, Toronto, ON, Canada M1C 1A4, Wang, Yanwen, Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3, & Sun, Changhao. Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes.  United States.  https://doi.org/10.1016/J.BBRC.2013.05.068

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                    He, Yonghan, Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3, State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Li, Ying, Zhang, Shuocheng, Perry, Ben, Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3, Zhao, Tiantian, Department of Psychology, University of Toronto, 1265 Military Trail, Toronto, ON, Canada M1C 1A4, Wang, Yanwen, Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3, and Sun, Changhao. 2013.  
        "Radicicol, a heat shock protein 90 inhibitor, inhibits differentiation and adipogenesis in 3T3-L1 preadipocytes".  United States.  https://doi.org/10.1016/J.BBRC.2013.05.068.

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@article{osti_22239640,

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

  author       = {He, Yonghan and Aquatic and Crop Resource Development, Life Sciences Branch, National Research Council Canada, Charlottetown, PE, Canada C1A 4P3 and State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 and Li, Ying and Zhang, Shuocheng and Perry, Ben and Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3 and Zhao, Tiantian and Department of Psychology, University of Toronto, 1265 Military Trail, Toronto, ON, Canada M1C 1A4 and Wang, Yanwen and Department of Biomedical Sciences, University of Prince Edward Island, 550 University Avenue, Charlottetown, PE, Canada C1A 4P3 and Sun, Changhao},

  abstractNote = {Highlights: •Radicicol suppressed intracellular fat accumulation in 3T3-L1 adipocytes. •Radicicol inhibited the expression of FAS and FABP4. •Radicicol blocked cell cycle at the G1-S phase during cell differentiation. •Radicicol inhibited the PDK1/Akt pathway in adipocyte differentiation. -- 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 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 (PPAR{sub γ}) and CCAAT element binding protein α (C/EBP{sub α}), 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.},

  doi          = {10.1016/J.BBRC.2013.05.068},

  url          = {https://www.osti.gov/biblio/22239640},
  journal      = {Biochemical and Biophysical Research Communications},

  issn         = {0006-291X},

  number       = 2,

  volume       = 436,

  place        = {United States},

  year         = {Fri Jun 28 00:00:00 EDT 2013},

  month        = {Fri Jun 28 00:00:00 EDT 2013}

}

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