Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Portugal, CC (Autor) Outra; Socodato, R (Autor) Outra; Canedo, T (Autor) Outra; Silva, CM (Autor) Outra; Martins, T (Autor) Outra; Coreixas, VSM (Autor) Outra; Loiola, EC (Autor) Outra; Gess, B (Autor) Outra; Roehr, D (Autor) Outra; Santiago, AR (Autor) Outra; Young, P (Autor) Outra; Minshall, RD (Autor) Outra; Paes de Carvalho, R (Autor) Outra; Ambrosio, AF (Autor) Outra; Relvas, JB (Autor) ICBAS

Revista

Título: Science Signaling

Vol. 10

ISSN: 1945-0877

Editora: American Association for the Advancement of Science

Indexação

ISI Web of Knowledge - 13 Citações

Scopus - 31 Citações

Outras Informações

ID Authenticus: P-00M-MF5

DOI: 10.1126/scisignal.aal2005

Abstract (EN): Vitamin C is essential for the development and function of the central nervous system (CNS). The plasma membrane sodium-vitamin C cotransporter 2 (SVCT2) is the primary mediator of vitamin C uptake in neurons. SVCT2 specifically transports ascorbate, the reduced form of vitamin C, which acts as a reducing agent. We demonstrated that ascorbate uptake through SVCT2 was critical for the homeostasis of microglia, the resident myeloid cells of the CNS that are essential for proper functioning of the nervous tissue. We found that depletion of SVCT2 from the plasma membrane triggered a proinflammatory phenotype in microglia and resulted in microglia activation. Src-mediated phosphorylation of caveolin-1 on Tyr(14) in microglia induced the internalization of SVCT2. Ascorbate treatment, SVCT2 overexpression, or blocking SVCT2 internalization prevented the activation of microglia. Overall, our work demonstrates the importance of the ascorbate transport system for microglial homeostasis and hints that dysregulation of ascorbate transport might play a role in neurological disorders.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 20