The effect of transforming growth factor beta-1 activation on the expression of NR1 subunit of NMDA receptor in a murine model of acute liver failure. Role of thrombospondin(s)

• Autorzy: Popek M. , Zielinska M.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: We have previously shown altered expression and/or intracellular distribution of selected synaptic proteins that may contribute to neurological dysfunction observed during acute liver failure (ALF) in mice. During ALF an increased level of TGF‑β1 in the serum and brain was also observed. Moreover, neutralization of TGF‑β1 appears to improve the neurological score of ALF mice. AIM(S): We test the hypothesis that thrombospondin(s) – related activation of TGF‑β1 may affect the expression of NR1, a major NMDA receptor subunit. METHOD(S): We measured total and active TGF‑β1 level in the brain and blood of C57Bl6 mice with ALF induced by single i.p. injection of azoxymethan (AOM; 100 mg/kg of b.w.) and after neutralization of TGF‑β1 induced by single i.p. injection of ab‑TGF‑ β1 (1 mg/kg) 2 h before AOM injection. In addition we analyzed the expression of thrombospondin-4 (Thrb4) and NR1 subunit in AOM brain homogenates and membrane/cytosolic fractions. RESULTS: In ALF mice, active form to total TGF‑β1 ratio was increased by ~35%,and ~30% in serum and rain cortex, respectively. Expression of Thrb4 was increased by ~30% in homogenates and by ~35% in cytosolic fraction. Both, AOM injection and TGF‑β1 neutralization induced the increase of NR1 subunit in membrane fraction, by ~40%, and ~60% respectively. CONCLUSIONS: The results indicate that in ALF mouse, neutralization of cytokine TGF‑β1 may cause an increase in NR1 expression, the effect not potentiated by AOM. The increase in the expression of Thrb4 play a potential role in the activation of TGF‑β1, as may be assumed from the increase in TGF‑β1 ratio in the serum and the brain homogenates. The particular mechanism requires an additional research. FINANCIAL SUPPORT: Supported by the grant Prelludium10 2015/19/N/NZ5/02249 and the Leading National Research Centre (KNOW).

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.97

Twórcy

autor

Popek M.

• Mossakowski Medical Resarch Centre, Department of Neurotoxicology, Warsaw, Poland

autor

Zielinska M.

• Mossakowski Medical Resarch Centre, Department of Neurotoxicology, Warsaw, Poland