O-GlcNAc transferase inhibits LPS-mediated expression of inducible nitric oxide synthase through an increased interaction with mSin3A in RAW264.7 cells.

Title
O-GlcNAc transferase inhibits LPS-mediated expression of inducible nitric oxide synthase through an increased interaction with mSin3A in RAW264.7 cells.
Authors
한인옥
Keywords
OGT; O-GlcNAc; c-Rel; mSin3A
Issue Date
2013
Publisher
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Series/Report no.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY ; Vol.305 no.6 Startpage C601 Endpage C608
Abstract
O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT), which catalyzes the addition of a single β-N-GlcNAc unit to target proteins, has been shown to act as a transcriptional regulator. In the current study, we discovered that OGT exerted inhibitory effects on the LPS-driven activation of NF-κB and inducible nitric oxide synthase (iNOS). In response to LPS, OGT exhibited an increased interaction with the transcriptional corepressor mammalian Sin3A (mSin3A). Furthermore, mSin3A, histone deacetylase (HDAC)1, and HDAC2 displayed increased binding to the iNOS promoter in response to LPS. Treatment with GlcN, in contrast, inhibits LPS-induced inflammation and decreased LPS-mediated recruitment of OGT, mSin3A, and HDACs. LPS treatment also resulted in the hypo-O-GlcNAcylation of mSin3A, which was reversed by GlcN. When the effect of the HDAC inhibitor trichostatin A (TSA) on LPS- and/or GlcN-mediated iNOS protein/mRNA induction was investigated, the results revealed that TSA dose dependently enhanced iNOS expression in response to LPS and/or GlcN. In addition, histone acetyltransferases, p300, and cAMP response element-binding protein-binding protein (CBP) enhanced LPS- and/or GlcN-induced iNOS protein expression. These results collectively suggest that OGT inhibits LPS-driven NF-κB activation and subsequent iNOS transcription by modulating histone acetylation either directly or indirectly.
URI
http://dspace.inha.ac.kr/handle/10505/31187
ISSN
0363-6143
Appears in Collections:
Medical School/College of Medicine (의학전문대학원/의과대학) > Medical Science (의학) > Journal Papers, Reports(의학 논문, 보고서)

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