title: Upregulation of zinc transporter 2 in the blood-CSF barrier following lead exposure.
abstract: Zinc (Zn) is an essential element for normal brain function; an abnormal Zn homeostasis in brain and the cerebrospinal fluid (CSF) has been implied in the etiology of Alzheimer's disease (AD). However, the mechanisms that regulate Zn transport in the blood-brain interface remain unknown. This study was designed to investigate Zn transport by the blood-CSF barrier (BCB) in the choroid plexus, with a particular focus on Zn transporter-2 (ZnT2), and to understand if lead (Pb) accumulation in the choroid plexus disturbed the Zn regulatory function in the BCB. Confocal microscopy, quantitative PCR and western blot demonstrated the presence of ZnT2 in the choroidal epithelia; ZnT2 was primarily in cytosol in freshly isolated plexus tissues but more toward the peripheral membrane in established choroidal Z310 cells. Exposure of rats to Pb (single ip injection of 50 mg Pb acetate/kg) for 24 h increased ZnT2 fluorescent signals in plexus tissues by confocal imaging and protein expression by western blot. Similar results were obtained by in vitro experiments using Z310 cells. Further studies using cultured cells and a two-chamber Transwell device showed that Pb treatment significantly reduced the cellular Zn concentration and led to an increased transport of Zn across the BCB, the effect that may be due to the increased ZnT2 by Pb exposure. Taken together, these results indicate that ZnT2 is present in the BCB; Pb exposure increases the ZnT2 expression in choroidal epithelial cells by a yet unknown mechanism and as a result, more Zn ions may be deposited into the intracellular Zn pool, leading to a relative Zn deficiency state in the cytoplasm at the BCB.
authors: School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors: Xue
authors: X
authors: Fu
authors: Andrew
authors: A
authors: Zeng
authors: Wei
authors: W
authors: Zheng
authors: Yansheng
authors: Y
authors: Du
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism; D006706:Homeostasis; D007854:Lead / Q000494:pharmacology*; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects*; D015032:Zinc / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; C099189:Slc30a2 protein, rat; D007854:Lead; D015032:Zinc
keywords: Z310 cells; Zinc (Zn); blood–CSF barrier; lead (Pb); zinc transporter 2 (ZnT2)