Activation of PPARγ negatively regulates O-GlcNAcylation of Sp1

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-G...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2008-08, Vol.372 (4), p.713-718
Main Authors: Chung, Sung Soo, Kim, Ji Hyun, Park, Ho Seon, Choi, Hye Hun, Lee, Kyeong Won, Cho, Young Min, Lee, Hong Kyu, Park, Kyong Soo
Format: Article
Language:English
Subjects:
O-GlcNAcylation
PPARγ
Sp1
Thiazolidinediones
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Summary: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 γ (PPARγ) activation and probably by synthesis of a specific protein induced by PPARγ 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:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.05.096