Zinc Potentiates Lipopolysaccharide-induced Nitric Oxide Production in Cultured Primary Rat Astrocytes.

We examined the effect of extracellularly applied Zn(2+) on nitric oxide (NO) production in primary cultured rat astrocytes, which were experimentally activated by lipopolysaccharide (LPS). Zn(2+), 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 Zn(2+). Zn(2+) also increased LPS-induced production of intracellular reactive oxygen species. Zn(2+) 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 Zn(2+). Intracellular Zn(2+) chelation with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) or inhibition of p38-MAPK diminished the Zn(2+) enhancement of LPS-induced NO production. These findings suggest that activation of MAPK and NFκB is important for mediating Zn(2+)enhancement of LPS-induced NO production in astrocytes. Such changes may exacerbate glial and neuronal damage during neuroinflammation.
PMID: 29124566 [PubMed - as supplied by publisher]

Source: Neurochemical Research - November 9, 2017 Category: Neuroscience Authors: Moriyama M, Fujitsuka S, Kawabe K, Takano K, Nakamura Y Tags: Neurochem Res Source Type: research