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Publication : Identification of the target proteins of rosiglitazone in 3T3-L1 adipocytes through proteomic analysis of cytosolic and secreted proteins.

First Author  Hwang HH Year  2011
Journal  Mol Cells Volume  31
Issue  3 Pages  239-46
PubMed ID  21347706 Mgi Jnum  J:317783
Mgi Id  MGI:6857633 Doi  10.1007/s10059-011-0026-6
Citation  Hwang HH, et al. (2011) Identification of the target proteins of rosiglitazone in 3T3-L1 adipocytes through proteomic analysis of cytosolic and secreted proteins. Mol Cells 31(3):239-46
abstractText  Rosiglitazone, one of the thiazolidinedione (TZD), is an oral antidiabetic drug that activates a gamma isoform of peroxisome proliferator-activated receptor (PPARgamma). To identify target proteins induced by rosiglitazone in adipocytes, we first performed simultaneous in-depth proteomic profiling of cytosolic proteins and secreted proteins (secretome) from 3T3-L1 adipocytes using a label-free quantification method with nano-UPLC MS/MS. In total, we identified 646 proteins from 3T3-L1 adipocytes, of which 172 and 162 proteins were upregulated and downregulated >1.5-fold, respectively, in rosiglitazone-treated cells, as compared to controls. Some differentially expressed proteins in particular, including fatty acid translocase (FAT)/CD36, fatty acid binding protein, lipoprotein lipase, acetyl CoA acyltransferase, carnitine O-palmitoyltransferase 2, sterol carrier protein, adiponectin, and phosphoenolpyruvate carboxykinase could explain the current action mechanism of TZDs. Furthermore, this study is the first to report on two potential target proteins of rosiglitazone, such as adenomatosis polyposis coli 2 (APC2), and eukaryotic translation initiation factor 5A-1 (eIF5A) related to apoptosis and cell division. Our data clearly suggest that in-depth proteomic approaches using cytosolic and secreted proteins are important and necessary for identification of drug targets at the protein level.
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