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Issue 5, 2013
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D-Histidine and L-histidine attenuate zinc-induced neuronal death in GT1-7 cells

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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 Zn2+. 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.

Graphical abstract: d-Histidine and l-histidine attenuate zinc-induced neuronal death in GT1-7 cells

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Publication details

The article was received on 25 Dec 2012, accepted on 19 Feb 2013 and first published on 20 Feb 2013


Article type: Paper
DOI: 10.1039/C3MT20264J
Metallomics, 2013,5, 453-460

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

    M. Kawahara, Y. Sadakane, H. Koyama, K. Konoha and S. Ohkawara, Metallomics, 2013, 5, 453
    DOI: 10.1039/C3MT20264J

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