title: Distribution of the zinc transporter ZnT-1 in comparison with chelatable zinc in the mouse brain.
abstract: 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 Zn(2+) 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 Zn(2+) 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 Zn(2+), 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 Zn(2+). 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 Zn(2+) homeostasis is required. This finding suggests a protective role for neuronal ZnT-1 in the context of both normal and pathophysiological activity.
authors: Department of Physiology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, 84 105 Israel.
authors: Israel
authors: I
authors: Sekler
authors: Arie
authors: A
authors: Moran
authors: Michal
authors: M
authors: Hershfinkel
authors: Amir
authors: A
authors: Dori
authors: Ariel
authors: A
authors: Margulis
authors: Nurit
authors: N
authors: Birenzweig
authors: Yuval
authors: Y
authors: Nitzan
authors: William F
authors: WF
authors: Silverman
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D027682:Cation Transport Proteins; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains / Q000033:anatomy & histology / Q000378:metabolism*; D019579:Neocortex / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D002614:Chelating Agents; D008565:Membrane Proteins; C485803:Slc30a1 protein, mouse; D015032:Zinc