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Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells

Title
Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells
Authors
Hwang, Ji-SunKwon, Mi-YounKim, Kyung-HongLee, YunkyoungLyoo, In KyoonKim, Jieun E.Oh, Eok-SooHan, Inn-Oc
Ewha Authors
오억수한인옥김지은류인균이윤경
SCOPUS Author ID
오억수scopus; 김지은scopus; 류인균scopus
Issue Date
2017
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
0021-9258JCR Link1083-351XJCR Link
Citation
vol. 292, no. 5, pp. 1724 - 1736
Keywords
glucoseinflammationNF-BO-GlcNAcylationO-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT)
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. However, GlcN suppressed NO/iNOS production under high glucose culture conditions. Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF- mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. Glucose itself dose dependently increased LPS-induced iNOS expression. LPS-induced MAPK and IB- phosphorylation did not significantly differ at normal and high glucose conditions. The activity of LPS-induced nuclear factor-B (NF-B) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. The NF-B inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. In addition, pyrrolidine dithiocarbamate inhibited NF-B DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess.
DOI
10.1074/jbc.M116.737940
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자연과학대학 > 생명과학전공 > Journal papers
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