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

Authors
  • Moriyama, Mitsuaki1
  • Fujitsuka, Shunsuke2
  • Kawabe, Kenji2, 3
  • Takano, Katsura2
  • Nakamura, Yoichi2
  • 1 Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai Kita, Izumisano, Osaka, 598-8531, Japan. [email protected] , (Japan)
  • 2 Laboratory of Integrative Physiology in Veterinary Sciences, Osaka Prefecture University, 1-58 Rinku-Ourai Kita, Izumisano, Osaka, 598-8531, Japan. , (Japan)
  • 3 Department of Regenerative Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. , (Japan)
Type
Published Article
Journal
Neurochemical Research
Publisher
Springer-Verlag
Publication Date
Feb 01, 2018
Volume
43
Issue
2
Pages
363–374
Identifiers
DOI: 10.1007/s11064-017-2431-5
PMID: 29124566
Source
Medline
Keywords
License
Unknown

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.

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