Papel da O-Glicosilação com N-Acetil-Glucosamina nas alterações vasculares modulada pela ERK 1/2 via Interleucina-10

Detalhes bibliográficos
Ano de defesa: 2017
Autor(a) principal: Miguez, Jéssica Silva Gonçalves
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Mato Grosso
Brasil
Instituto de Ciências Biológicas e da Saúde (ICBS) – Araguaia
UFMT CUA - Araguaia
Programa de Pós-Graduação em Imunologia e Parasitologia Básicas e Aplicadas
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://ri.ufmt.br/handle/1/4173
Resumo: O-Glycosylation with N-acetyl-glucosamine (O-GlcNAc) is defined as a post-translational modification that acts on several signaling pathways, among which we have proteins with important role in vascular function. On the other hand, several authors have demonstrated that the absence of interleukin-10 (IL-10) may favor vascular dysfunction. The objective of this study was to verify if O-GlcNAc promotes alteration in vasoconstriction by kinase modulators regulated by extracellular signals (ERK 1/2) via IL-10. For this, aorta of male C57BL / 6 mice (12 weeks) were incubated with Thiamet G (1 μM for 24 hours - selective OGA inhibitor capable of increasing overall levels of O-GlcNAc). Knockout mice for IL-10 (IL-10 -/-: B6.129P2- Il10tm1Cgn / J; 12 weeks) were also used. Vascular reactivity (n= 6) and western blot tests were performed to evaluate protein expression. The vessels of IL-10 -/- mice show a greater vasoconstriction for phenylephrine when compared to the control [Emax (% KCl) = 203.6 ± 8.39 vs 163.0 ± 10.64] and the same can be observed (Emax (% KCl) = 167.9 ± 3.46 vs. 126.1 ± 3.23), but incubation with an ERK 1/2 inhibitor prevented these effects (Emax (% KCl) = IL-10 -/- = 120.7 ± 5.40, Thiamet G = 144.2 ± 1.89). Western blot analysis revealed that IL-10 -/- mice showed an increase in ERK 1/2 expression (p = 0.0001), as well as vessels treated with Thiamet G (p = 0.0119), which also expressed more O-Glycosylated proteins (p = 0.0250). The OGT enzyme remained unchanged, whereas OGA expression was elevated (p = 0.0285). Regarding the IL-10 signaling pathway, it was observed that although the JAK1 enzyme is more expressed (p= 0.0287) in the vessels incubated with Thiamet G, STAT3 expression is decreased (p= 0.0048), which resulted in lower IL-10 tissue levels (p= 0.0001). These data suggest that increased OGlcNAc is able to increase ERK 1/2 activity and this effect is mediated by the decrease in the IL10 signaling pathway, which may result in vascular dysfunction.