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Activation of PPARgamma negatively regulates O-GlcNAcylation of Sp1

Cited 17 time in Web of Science Cited 19 time in Scopus
Issue Date
2008-06-03
Publisher
Elsevier
Citation
Biochem Biophys Res Commun. 372 (2008) 713–718
Keywords
Acetylglucosamine/biosynthesis/*metabolismAcylation/drug effectsAnimalsCell LineHumansHyperglycemia/metabolismHypoglycemic Agents/*pharmacologyInsulin ResistanceMaleMiceMice, Inbred C57BLPPAR gamma/*agonistsProtein Processing, Post-Translational/*drug effectsSp1 Transcription Factor/*metabolismThiazolidinediones/*pharmacologyTranscription, GeneticZinc Fingers
Abstract
O-GlcNAcylation is a kind of post-translational modification and many nuclear and cytoplasmic proteins are O-GlcNAcylated. In this study, we demonstrated that thiazolidinediones (TZDs), which are used as insulin sensitizer, specifically inhibited the O-GlcNAcylation of Sp1 but did not affect the O-GlcNAcylation of the total proteins in cell culture systems and mouse models. This effect was mediated by peroxisome proliferator activated receptor gamma (PPARgamma) activation and probably by synthesis of a specific protein induced by PPARgamma activation. In addition, we demonstrated that the O-GlcNAcylation sites in the zinc-finger domain were involved in the transcriptional activation of Sp1 and that rosiglitazone, a member of TZDs, affected Sp1 transcriptional activity partially by regulating the O-GlcNAcylation level of these sites. Considering the role of hexosamine biosynthesis pathway in hyperglycemia-induced insulin resistance and Sp1 in the hyperglycemia-induced gene expression, the regulation of Sp1 O-GlcNAcylation by TZDs may help to explain the function of TZDs as a treatment for insulin resistance and diabetes.
ISSN
1090-2104 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18513490

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WBK-4SM6R6T-1-9&_cdi=6713&_user=168665&_orig=search&_coverDate=08%2F08%2F2008&_sk=996279995&view=c&wchp=dGLzVtb-zSkWb&md5=5c07d07cb563206772d0313dd3c41a0f&ie=/sdarticle.pdf

https://hdl.handle.net/10371/68184
DOI
https://doi.org/10.1016/j.bbrc.2008.05.096
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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