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 Citations (Scopus)

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

Fingerprint

Glycosylation
Acetylglucosamine
Interleukin-10
Blood Vessels
Phosphorylation
Interleukin-10 Receptors
Cytokines
Proteins
Post Translational Protein Processing
Inbred C57BL Mouse
Knockout Mice
Medical problems
Aorta
Arteries
Western Blotting

Keywords

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

ASJC Scopus subject areas

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

Cite this

Miguez, J. S. G., Dela Justina, V., Bressan, A. F. M., Marchi, P. G. F., Honorio-França, A. C., Carneiro, F. S., ... 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

O-Glycosylation with O-linked β-N-acetylglucosamine increases vascular contraction : Possible modulatory role on Interleukin-10 signaling pathway. / Miguez, Jéssica S.G.; Dela Justina, Vanessa; Bressan, Alecsander F.M.; Marchi, Patrícia G.F.; Honorio-França, Adenilda C.; Carneiro, Fernando S.; Webb, R Clinton; Tostes, Rita C.; Giachini, Fernanda R.; Lima, Victor V.

In: Life sciences, Vol. 209, 15.09.2018, p. 78-84.

Research output: Contribution to journalReview article

Miguez, JSG, Dela Justina, V, Bressan, AFM, Marchi, PGF, Honorio-França, AC, Carneiro, FS, Webb, RC, Tostes, RC, Giachini, FR & Lima, VV 2018, 'O-Glycosylation with O-linked β-N-acetylglucosamine increases vascular contraction: Possible modulatory role on Interleukin-10 signaling pathway', Life sciences, vol. 209, pp. 78-84. https://doi.org/10.1016/j.lfs.2018.07.058
Miguez, Jéssica S.G. ; Dela Justina, Vanessa ; Bressan, Alecsander F.M. ; Marchi, Patrícia G.F. ; Honorio-França, Adenilda C. ; Carneiro, Fernando S. ; Webb, R Clinton ; Tostes, Rita C. ; Giachini, Fernanda R. ; Lima, Victor V. / O-Glycosylation with O-linked β-N-acetylglucosamine increases vascular contraction : Possible modulatory role on Interleukin-10 signaling pathway. In: Life sciences. 2018 ; Vol. 209. pp. 78-84.
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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.",
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T2 - Possible modulatory role on Interleukin-10 signaling pathway

AU - Miguez, Jéssica S.G.

AU - Dela Justina, Vanessa

AU - Bressan, Alecsander F.M.

AU - Marchi, Patrícia G.F.

AU - Honorio-França, Adenilda C.

AU - Carneiro, Fernando S.

AU - Webb, R Clinton

AU - Tostes, Rita C.

AU - Giachini, Fernanda R.

AU - Lima, Victor V.

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AB - 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.

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KW - O-GlcNAc

KW - Vascular dysfunction

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