RBE4 cells are highly resistant to paraquat-induced cytotoxicity: studies on uptake and efflux mechanisms

• Tipo: Artigo em Revista Científica Internacional
• Data: 2014

Autores

Vilas Boas, V (Autor) Outra; Silva, R (Autor) Outra; Guedes de Pinho, P (Autor) FFUP; Carvalho, F (Autor) FFUP; Bastos, ML (Autor) FFUP; Remiao, F (Autor) FFUP

Revista

Título: Journal of Applied Toxicology

Vol. 34 Nº 6

Páginas: 1023-1030

ISSN: 0260-437X

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 12 Citações

Scopus - 16 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-008-PJK

DOI: 10.1002/jat.2926

Abstract (EN): Paraquat (PQ) is a widely used, highly toxic and non-selective contact herbicide, which has been associated with central neurotoxic effects, namely the development of Parkinson's disease, but whose effects to the blood-brain barrier (BBB) itself have rarely been studied. This work studied the mechanisms of PQ uptake and efflux in a rat's BBB cell model, the RBE4 cells. PQ is believed to enter cells using the basic or neutral amino acid or polyamine transport systems or through the choline-uptake system. In contrast, PQ efflux from cells is reported to bemediated by P-glycoprotein. Therefore, we evaluated PQ-induced cytotoxicity and the effect of some substrates/blockers of these transporters (such as arginine, L-valine, putrescine, hemicholinium-3 and GF120918) on such cytotoxicity. RBE4 cells were shown to be extremely resistant to PQ after 24 h of exposure; even at concentrations as high as 50 mM approximately 45% of the cells remained viable. Prolonging exposure until 48 h elicited significant cytotoxicity only for PQ concentrations above 5 mM. Although hemicholinium-3, a choline-uptake system inhibitor, significantly protected cells against PQ-induced toxicity, none of the effects were observed for arginine, L-valine or putrescine. Meanwhile, inhibiting the efflux pump P-glycoprotein using GF120918 significantly enhanced PQ-induced cytotoxicity. In conclusion, PQ used the choline-uptake system, instead of the transporters for the basic or neutral amino acids or for the polyamines, to enter RBE4 cells. P-glycoprotein extrudes PQ back to the extracellular medium. However, this efflux mechanism only partially explains the observed RBE4 resistance to PQ. Copyright (C) 2013 John Wiley & Sons, Ltd.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8