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Neurochem Res ; 43(2): 363-374, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29124566

RESUMO

Zn2+ plays a crucial role in the CNS where it accumulates in synaptic vesicles and is released during neurotransmission. Synaptically released Zn2+ is taken up by neurons and astrocytes. The majority of previous work has focused on neuronal damage caused by excess Zn2+. However, its effect on astrocyte function is not well understood. We examined the effect of extracellularly applied Zn2+ on nitric oxide (NO) production in primary cultured rat astrocytes, which were experimentally activated by lipopolysaccharide (LPS). Zn2+, at a concentration up to 125 µM, augmented LPS-induced NO production without affecting cell viability. LPS induced expression of both mRNA and protein of inducible NO synthase; this expression was enhanced by 125 µM Zn2+. Zn2+ also increased LPS-induced production of intracellular reactive oxygen species. Zn2+ enhanced the phosphorylation of p38-mitogen-activated protein kinase (MAPK) at 1-6 h after LPS treatment. The LPS-induced nuclear factor-kappaB (NFκB) activation was sustained for 6 h by Zn2+. Intracellular Zn2+ chelation with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) or inhibition of p38-MAPK diminished the Zn2+ enhancement of LPS-induced NO production. These findings suggest that activation of MAPK and NFκB is important for mediating Zn2+enhancement of LPS-induced NO production in astrocytes. Such changes may exacerbate glial and neuronal damage during neuroinflammation.


Assuntos
Astrócitos/metabolismo , Lipopolissacarídeos/farmacologia , Neurônios/metabolismo , Óxido Nítrico/metabolismo , Zinco/metabolismo , Animais , Células Cultivadas , Microglia/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neuroglia/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
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