RGD Reference Report - Glucosamine improves cardiac function following trauma-hemorrhage by increased protein O-GlcNAcylation and attenuation of NF-{kappa}B signaling. - Rat Genome Database

RGD Reference Report - Glucosamine improves cardiac function following trauma-hemorrhage by increased protein O-GlcNAcylation and attenuation of NF-{kappa}B signaling. - Rat Genome Database

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Glucosamine improves cardiac function following trauma-hemorrhage by increased protein O-GlcNAcylation and attenuation of NF-{kappa}B signaling.
Authors:	Zou, L Yang, S Champattanachai, V Hu, S Chaudry, IH Marchase, RB Chatham, JC
Citation:	Zou L, etal., Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H515-23. doi: 10.1152/ajpheart.01025.2008. Epub 2008 Dec 19.
RGD ID:	9590190
Pubmed:	PMID:19098112 (View Abstract at PubMed)
PMCID:	PMC2643896 (View Article at PubMed Central)
DOI:	DOI:10.1152/ajpheart.01025.2008 (Journal Full-text)
We have previously demonstrated that in a rat model of trauma-hemorrhage (T-H), glucosamine administration during resuscitation improved cardiac function, reduced circulating levels of inflammatory cytokines, and increased tissue levels of O-linked N-acetylglucosamine (O-GlcNAc) on proteins. The mechanism(s) by which glucosamine mediated its protective effect were not determined; therefore, the goal of this study was to test the hypothesis that glucosamine treatment attenuated the activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway in the heart via an increase in protein O-GlcNAc levels. Fasted male rats were subjected to T-H by bleeding to a mean arterial blood pressure of 40 mmHg for 90 min followed by resuscitation. Glucosamine treatment during resuscitation significantly attenuated the T-H-induced increase in cardiac levels of TNF-alpha and IL-6 mRNA, IkappaB-alpha phosphorylation, NF-kappaB, NF-kappaB DNA binding activity, ICAM-1, and MPO activity. LPS (2 microg/ml) increased the levels of IkappaB-alpha phosphorylation, TNF-alpha, ICAM-1, and NF-kappaB in primary cultured cardiomyocytes, which was significantly attenuated by glucosamine treatment and overexpression of O-GlcNAc transferase; both interventions also significantly increased O-GlcNAc levels. In contrast, the transfection of neonatal rat ventricular myocytes with OGT small-interfering RNA decreased O-GlcNAc transferase and O-GlcNAc levels and enhanced the LPS-induced increase in IkappaB-alpha phosphorylation. Glucosamine treatment of macrophage cell line RAW 264.7 also increased O-GlcNAc levels and attenuated the LPS-induced activation of NF-kappaB. These results demonstrate that the modulation of O-GlcNAc levels alters the response of cardiomyocytes to the activation of the NF-kappaB pathway, which may contribute to the glucosamine-mediated improvement in cardiac function following hemorrhagic shock.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
cellular response to lipopolysaccharide		IMP		9590190		RGD

Objects Annotated

Genes (Rattus norvegicus)

Ogt (O-linked N-acetylglucosamine (GlcNAc) transferase)

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