Distribution of the zinc transporter ZnT-1 in comparison with chelatable zinc in the mouse brain

被引:78
作者
Sekler, I
Moran, A
Hershfinkel, M
Dori, A
Margulis, A
Birenzweig, N
Nitzan, Y
Silverman, WF
机构
[1] Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, Dept Morphol, IL-84105 Beer Sheva, Israel
[2] Ben Gurion Univ Negev, Zlotowski Ctr Neurosci, Dept Physiol, IL-84105 Beer Sheva, Israel
关键词
metallothionein; transition metals; zinc-containing neuron;
D O I
10.1002/cne.10224
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Zinc maintains a diverse array of functions in the mammalian central nervous system as a key component of numerous enzymes, via its role in the activation of transcription factors, and as a neuroregulator, modulating neuronal receptors such as N-methyl-D-aspartate and gamma-aminobutyric acid. Zinc has a dark side, however, with massive influx of Zn2+ to neurons considered to be a key factor in neuronal death secondary to ischemia and seizure. Several different putative zinc transporters, ZnT-1-4, have recently been identified and characterized. Among them, ZnT-1 has been suggested to play a key role in reducing cellular Zn2+ toxicity. In the present study, we describe the regional and cellular distribution of ZnT-1 in the adult mouse brain using an antibody raised against the C-terminal domain of mouse ZnT-1. The distribution of ZnT-1 was compared to that of chelatable Zn2+, visualized by means of neoTimm histochemistry or N-(6-methoxy-8-quinolyl)-p-toluene-sulfonamide (TSQ) histofluorescence. Extracts from various brain regions specifically stained a 60-kDa peptide corresponding to the expected molecular weight of ZnT-1. The expression of ZnT-1 was highest in the cerebral cortex and cerebellum, moderate in the hippocampus, hypothalamus, and olfactory bulb, and lowest in the striatum and septum. In brain sections, ZnT-1-immunoreactive neurons, in particular principle neurons, in the somatosensory cortex, hippocampus, and olfactory bulb, were closely related to synaptic Zn2+. Robust ZnT-1 immunoreactivity was also observed in cerebellar Purkinje cells. Although the function of the protein in these cells is unclear, in the forebrain, ZnT-1 is strikingly present in cells and regions where significant Zn2+ homeostasis is required. This finding suggests a protective role for neuronal ZnT-1 in the context of both normal and pathophysiological activity. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:201 / 209
页数:9
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