O-Glycosylation with O-linked ß-N-acetylglucosamine increases vascular contraction: Possible modulatory role on Interleukin-10 signaling pathway.
Life Sci
; 209: 78-84, 2018 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-30075176
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 ß-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. MAINMETHODS:
Mice (C57BL/6) aortic segments were incubated with vehicle or Thiamet G (0.1â¯mM, for 24â¯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. KEYFINDINGS:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetilglucosamina
/
Vasoconstrição
/
Processamento de Proteína Pós-Traducional
/
Interleucina-10
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article