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

Mitsuaki Moriyama, Shunsuke Fujitsuka, Kenji Kawabe, Katsura Takano, Yoichi Nakamura

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)363-374
Number of pages12
JournalNeurochemical Research
Volume43
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

Keywords

  • Mitogen-activated protein kinase
  • NFκB
  • Neuroinflammation
  • Oxidative stress
  • Zn

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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