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Brain Res ; 1624: 175-187, 2015 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-26236024

RESUMO

Methamphetamine (Meth) abuse can lead to the breakdown of the blood-brain barrier (BBB) integrity leading to compromised CNS function. The role of Galectins in the angiogenesis process in tumor-associated endothelial cells (EC) is well established; however no data are available on the expression of Galectins in normal human brain microvascular endothelial cells and their potential role in maintaining BBB integrity. We evaluated the basal gene/protein expression levels of Galectin-1, -3 and -9 in normal primary human brain microvascular endothelial cells (BMVEC) that constitute the BBB and examined whether Meth altered Galectin expression in these cells, and if Galectin-1 treatment impacted the integrity of an in-vitro BBB. Our results showed that BMVEC expressed significantly higher levels of Galectin-1 as compared to Galectin-3 and -9. Meth treatment increased Galectin-1 expression in BMVEC. Meth induced decrease in TJ proteins ZO-1, Claudin-3 and adhesion molecule ICAM-1 was reversed by Galectin-1. Our data suggests that Galectin-1 is involved in BBB remodeling and can increase levels of TJ proteins ZO-1 and Claudin-3 and adhesion molecule ICAM-1 which helps maintain BBB tightness thus playing a neuroprotective role. Galectin-1 is thus an important regulator of immune balance from neurodegeneration to neuroprotection, which makes it an important therapeutic agent/target in the treatment of drug addiction and other neurological conditions.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Células Endoteliais/efeitos dos fármacos , Galectina 1/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Metanfetamina/farmacologia , Fármacos Neuroprotetores/farmacologia , Encéfalo/citologia , Proteína de Ligação a CREB/metabolismo , Permeabilidade Capilar/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Claudina-5/genética , Claudina-5/metabolismo , Citocinas/genética , Citocinas/metabolismo , Interações Medicamentosas , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
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