| 3T3-L1 adipocyte apoptosis induced by thiazolidinediones is peroxisome proliferator-activated receptor-gamma-dependent and mediated by the caspase-3-dependent apoptotic pathway. | |
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MedLine Citation:
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PMID: 20050918 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although thiazolidinediones (TZDs) are potent promoters of adipogenesis in the preadipocyte, they induce apoptosis in several other cell types, such as cancer cells, endothelial cells and T-lymphocytes. In this study, we investigated the proapoptotic effect of TZDs in mature 3T3-L1 adipocytes, which express high levels of the peroxisome proliferator-activated receptor-gamma (PPARgamma) protein. Apoptosis was induced in mature 3T3-L1 adipocytes by treatment with troglitazone, pioglitazone or prostaglandin J2, and could be blocked by the PPARgamma antagonist GW9662. Treatment with PPARgamma agonists also decreased Akt-1 protein and phosphorylation levels without affecting phosphoinositide 3-kinase and PTEN. Further analysis indicated that in troglitazone-treated 3T3-L1 adipocytes, Bad phosphorylation and Bcl-2 protein levels were reduced, and Bax translocation to the mitochondria was increased. Subsequently, cytochrome c release and caspase-3 cleavage were observed. TZD-induced adipocyte apoptosis could be blocked by the caspase-3 inhibitor Ac-DEVD-CHO or by overexpression of Bcl2. In cultured rat primary adipocytes, similar apoptosis-inducing effects of troglitazone were also observed. Thus, TZDs promote apoptosis in adipocytes through a PPARgamma-dependent pathway. This apoptosis is mediated by the inhibition of Akt-1, which decreases Bad phosphorylation and activates the mitochondrial apoptotic pathway. |
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Authors:
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Yuanyuan Xiao; Taichang Yuan; Wenqi Yao; Kan Liao |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-29 |
Journal Detail:
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Title: The FEBS journal Volume: 277 ISSN: 1742-4658 ISO Abbreviation: FEBS J. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-09 Completed Date: 2010-03-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101229646 Medline TA: FEBS J Country: England |
Other Details:
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Languages: eng Pagination: 687-96 Citation Subset: IM |
Affiliation:
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State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Adipocytes / pathology, physiology* Animals Apoptosis / drug effects* Caspase 3 / metabolism* Chromans / pharmacology* Male Mice PPAR gamma / agonists, antagonists & inhibitors, physiology* Prostaglandin D2 / analogs & derivatives, pharmacology Proto-Oncogene Proteins c-akt / antagonists & inhibitors Proto-Oncogene Proteins c-bcl-2 / physiology Rats Rats, Zucker Thiazolidinediones / pharmacology* bcl-Associated Death Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Chromans; 0/PPAR gamma; 0/Proto-Oncogene Proteins c-bcl-2; 0/Thiazolidinediones; 0/bcl-Associated Death Protein; 111025-46-8/pioglitazone; 41598-07-6/Prostaglandin D2; 60203-57-8/9-deoxy-delta-9-prostaglandin D2; 97322-87-7/troglitazone; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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