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Metallomics. 2013 May;5(5):453-60. doi: 10.1039/c3mt20264j. Epub 2013 Mar 18.

D-histidine and L-histidine attenuate zinc-induced neuronal death in GT1-7 cells.

Author information

1
Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, 1-1-20 Shinmachi, Nishitokyo-shi, Tokyo 202-8585, Japan. makawa@musashino-u.ac.jp

Abstract

Although zinc (Zn) is an essential trace element, excess Zn causes neuronal death following transient global ischemia and plays a central role in the pathogenesis of vascular-type dementia. In this study, we developed a rapid and convenient screening system for substances that prevent Zn-induced neurotoxicity by using GT1-7 cells (immortalized hypothalamic neurons), with the aim of identifying a treatment for vascular-type dementia. Among tested, we found a protective substance in the extract of round herring (Etrumeus teres), and determined its structure as l-histidine. Analysis of the structure-activity relationship by using histidine analogues revealed that both l-histidine and d-histidine exhibit the same neuroprotective activity. Furthermore, we investigated the molecular mechanisms underlying the protective effect of histidine on Zn-induced neurotoxicity using Zn imaging and gene expression analysis, and found that histidine protects against Zn-induced neurotoxicity not by inhibiting Zn chelation, thereby preventing increases in intracellular Zn(2+). Moreover, it is also suggested that endoplasmic reticulum (ER) stress and activity-regulated cytoskeleton associated protein (Arc) are implicated in Zn-induced degeneration of neurons.

PMID:
23503404
DOI:
10.1039/c3mt20264j
[Indexed for MEDLINE]

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