期刊
LIFE SCIENCES
卷 209, 期 -, 页码 78-84出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.07.058
关键词
Cytokine; Vascular dysfunction; O-GlcNAc; ERK 1/2
资金
- Fundacao de Amparo a Pesquisa do Estado de Mato Grosso [(FAPEMAT) [211917/2015]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [(CNPq)] in Brazil [45777/2014-1]
Aims: The interleukin-10 (IL-10) is an immuno-regulatory cytokine that plays a protective effect in the vasculature. IL-10 binding to its receptor, activating the IL-10/JAK1/STAT3 cascade to exert its effects. Therefore, STAT3 phosphorylation is essential for IL-10 actions. O-Glycosylation with linked beta-N-acetylglucosamine (O-GlcNAc) is a post-translational modification able to regulate many proteins by interfering with protein on a phosphorylation level. Our aim was to determine whether O-GlcNAc promotes the inhibition of IL-10-pathway (JAK1/STAT3/IL-10), inactivationg its action in the vasculature. Main methods: Mice (C57BL/6) aortic segments were incubated with vehicle or Thiamet G (0.1 mM, for 24 h) to increase global O-GlcNAc levels. Aortas from knockout mice for IL-10 were also used. Vascular reactivity and western blot tests were performed to evaluate protein expression. Key findings: High levels of O-GlcNAc, induced by Thiamet G incubation, increased vascular expression of JAK1, but decreased expression and activity of STAT3. In addition, IL-10 levels were diminished in arteries treated with Thiamet G. Absence of IL-10, as well as augmented O-GlcNAcylation, increased vascular reactivity to constrictor stimuli, an effect that was abolished by ERK 1/2 inhibitor. High levels of O-GlcNAc and the absence of IL-10 also leads to increased vascular expression of ERK1/2. Significance: Our data suggest that O-GlcNAc modification seems to (dys) regulate IL-10 signaling pathway and consequently, compromise the protective effect of this cytokine in vasculature. It is possible that there is a promising relationship in pathophysiological conditions where changes in O-GlcNAcylation and IL-10 levels are observed, such as hypertension and diabetes.
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