O-Glycosylation with O-linked β-N-acetylglucosamine increases vascular contraction: Possible modulatory role on Interleukin-10 signaling pathway

Jéssica S.G. Miguez, Vanessa Dela Justina, Alecsander F.M. Bressan, Patrícia G.F. Marchi, Adenilda C. Honorio-França, Fernando S. Carneiro, R Clinton Webb, Rita C. Tostes, Fernanda R. Giachini, Victor V. Lima

Research output: Contribution to journalReview article

2 Scopus citations

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)78-84
Number of pages7
JournalLife sciences
Volume209
DOIs
StatePublished - Sep 15 2018

Keywords

  • Cytokine
  • ERK 1/2
  • O-GlcNAc
  • Vascular dysfunction

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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  • Cite this

    Miguez, J. S. G., Dela Justina, V., Bressan, A. F. M., Marchi, P. G. F., Honorio-França, A. C., Carneiro, F. S., Webb, R. C., Tostes, R. C., Giachini, F. R., & Lima, V. V. (2018). O-Glycosylation with O-linked β-N-acetylglucosamine increases vascular contraction: Possible modulatory role on Interleukin-10 signaling pathway. Life sciences, 209, 78-84. https://doi.org/10.1016/j.lfs.2018.07.058