Relative contribution of CTR1 and DMT1 in copper transport by the blood-CSF barrier: implication in manganese-induced neurotoxicity.

ABSTRACT: The homeostasis of copper (Cu) in the cerebrospinal fluid (CSF) is partially regulated by the Cu transporter-1 (CTR1) and divalent metal transporter-1 (DMT1) at the blood-CSF barrier (BCB) in the choroid plexus. Data from human and animal studies suggest an increased Cu concentration in blood, CSF, and brains following in vivo manganese (Mn) exposure. This study was designed to investigate the relative role of CTR1 and DMT1 in Cu transport under normal or Mn-exposed conditions using an immortalized choroidal Z310 cell line. Mn exposure in vitro resulted in an increased cellular 64Cu uptake and the up-regulation of both CTR1 and DMT1. Knocking down CTR1 by siRNA counteracted the Mn-induced increase of 64Cu uptake, while knocking down DMT1 siRNA resulted in an increased cellular 64Cu uptake

SUBMITTER: Zheng G 

PROVIDER: S-EPMC3336026 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature