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Activation of PPARgamma negatively regulates O-GlcNAcylation of Sp1
Cited 18 time in
Web of Science
Cited 20 time in Scopus
- Authors
- Issue Date
- 2008-06-03
- Publisher
- Elsevier
- Citation
- Biochem Biophys Res Commun. 372 (2008) 713–718
- Keywords
- Acetylglucosamine/biosynthesis/*metabolism ; Acylation/drug effects ; Animals ; Cell Line ; Humans ; Hyperglycemia/metabolism ; Hypoglycemic Agents/*pharmacology ; Insulin Resistance ; Male ; Mice ; Mice, Inbred C57BL ; PPAR gamma/*agonists ; Protein Processing, Post-Translational/*drug effects ; Sp1 Transcription Factor/*metabolism ; Thiazolidinediones/*pharmacology ; Transcription, Genetic ; Zinc 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
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