Longitudinal changes in zinc transport kinetics, metallothionein and zinc transporter expression in a blood–brain barrier model in response to a moderately excessive zinc environment

• Published in: The Journal of nutritional biochemistry Vol. 19; no. 2; pp. 129 - 137
• Main Authors: Bobilya, Dennis J., Gauthier, Nicole A., Karki, Shakun, Olley, Bryony J., Thomas, W. Kelly
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-02-2008; New York, NY: Elsevier Science; Elsevier Science
• Subjects: Amino Acid Sequence; animal models; Animals; Base Sequence; Biological and medical sciences; Biological Transport; Blood-Brain Barrier; brain; brain zinc homeostasis; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; cell culture; Cells, Cultured; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; cytotoxicity; diet-related diseases; dietary mineral supplements; dietary minerals; DNA Primers; endothelial cells; Fundamental and applied biological sciences. Psychology; Homeostasis; Kinetics; long term effects; longitudinal studies; megadose; Metallothionein; Metallothionein - metabolism; Molecular Sequence Data; neuroglia; neurological development; neurological function; neurons; neurophysiology; nutrient deficiencies; nutrient excess; nutrient transport; nutrition-genotype interaction; oxidative stress; RNA, Messenger - genetics; Swine; Swine, Miniature; toxicity testing; Vertebrates: nervous system and sense organs; zinc; Zinc - metabolism; Zinc homeostasis; Zinc toxicity; zinc transport rates; Zinc transporters; Zinc transporters; Zinc toxicity; Zinc homeostasis; Metallothionein; Blood–brain barrier; Toxicity; Biological transport; Central nervous system; Homeostasis; Gene expression; Blood brain barrier; Zinc; Encephalon; Pig; Vertebrata; Mammalia; Blood-brain barrier; Models; Artiodactyla; Kinetics; Ungulata; Carrier protein
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2007.06.014

A blood–brain barrier (BBB) model composed of porcine brain capillary endothelial cells (BCEC) was exposed to a moderately excessive zinc environment (50 μmol/L Zn) in cell culture, and longitudinal measurements were made of zinc transport kinetics, ZnT-1 (
SLC30A1) expression and changes in the protein concentration of metallothionein (MT), ZnT-1, ZnT-2 (SLC30A2) and Zip1 (SLC39A1). Zinc release by cells of the BBB model significantly increased after 12–24 h of exposure, but decreased back to control levels after 48–96 h, as indicated by transport across the BBB from both the ablumenal (brain) and the lumenal (blood) directions. Expression of ZnT-1, the zinc export protein, increased by 169% within 12 h, but was no longer different from controls after 24 h. Likewise, ZnT-1 protein content increased transiently after 12 h of exposure, but returned to control levels by 24 h. Capacity for zinc uptake and retention increased from both the lumenal and the ablumenal directions within 12–24 h of exposure and remained elevated. MT and ZnT-2 were elevated within 12 h and remained elevated throughout the study. Zip1 was unchanged by the treatment. The BBB's response to a moderately high zinc environment was dynamic and involved multiple mechanisms. The initial response was to increase the cells' capacity to sequester zinc with additional MT and to increase zinc export with the ZnT-1 protein. But the longer-term strategy involved increasing ZnT-2 transporters, presumably to sequester zinc into intracellular vesicles as a mechanism to protect the brain and to maintain brain zinc homeostasis.