Metal transporters in intestine and brain: Their involvement in metal-associated neurotoxicities

Joseph P. Bressler, Luisa Olivi, Hoon Cheong Jae, Yongbae Kim, Alex Maerten, Desmond Bannon

Research output: Contribution to journalArticlepeer-review

Abstract

The transport of essential metals and other nutrients across tight membrane barriers such as the gastrointestinal tract and blood-brain barrier is mediated by specific transport mechanisms. Specific transporters take up metals at the apical surface and export them at the basolateral surface, and are involved in their intracellular distribution. Transporters for each of the major essential metals, calcium, iron and zinc, have been identified. These transporters also mediate the transport of non-essential metals across tight membrane barriers. For example, the intestinal iron transporter divalent metal transporter 1 mediates the uptake of lead and cadmium. The levels of essential metals are strictly regulated by transporters. When dietary levels of essential metals are low, levels of the corresponding transporters increase in the intestine, after which there is a greater potential for increased transport of toxic metals. In the brain, the strict regulation of metals prevents injury that potentially would result from oxidative damage induced by the essential metals iron, copper and zinc. Indeed, the oxidative damage found in neurodegenerative diseases is likely to be due to higher levels of these metals. Involvement of intracellular transporters for copper and zinc has been shown in animal models of Alzheimer's disease, raising the possibility that higher levels of iron, zinc and copper might be due to a disruption in the activity of transporters. Accordingly, exposure to toxicants that affect the activity of transporters potentially could contribute to the aetiology/progression of neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalHuman and Experimental Toxicology
Volume26
Issue number3
DOIs
StatePublished - Mar 2007

Keywords

  • Brain
  • Disease
  • Intestine
  • Metals
  • Transporters

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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