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CHARACTERIZATION OF THE 8-TRANSMEMBRANE ZIP8 TRANSPORTER: EVIDENCE OF INTRACELLULAR TRAFFICKING IN RESPONSE TO EXTRACELLULAR METAL CONCENTRATIONS

REED, JODIE MICHELLE
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187007206

Abstract Details

2007, MS, University of Cincinnati, Medicine : Toxicology (Environmental Health).
Cadmium (Cd 2+, Cd) is a non-essential toxic metal, ubiquitous in the environment. The two most common sources in humans include cigarette smoke and Cd- contaminated foods such as shellfish. Cd uptake occurs principally via the intestine and lung, after which the metal accumulates in the liver, reproductive organs and kidney; kidney is ultimately the main target organ. The primary target of Cd in the kidney is the proximal convoluted tubule. The mechanism(s) of Cd toxicity and carcinogenicity are not well understood, although it is recognized that Cd exerts its effects inside the cell. Previous studies in our lab have shown that the mouse Slc39a8gene encodes ZIP8, a ubiquitous transporter responsible for Cd-induced testicular necrosis and renal failure. Using mouse fetal fibroblasts (MFFs) engineered to express ZIP8, our lab has found that essential metal substrates appear to include Mn 2+and Zn 2+; movement into the cell requires HCO 3 –ion, indicating that ZIP8 is a divalent metal ion/bicarbonate symporter. Cd is a rogue hitchhiker able to displace Mn or Zn and gain cell entry. My studies extended this work to Madin-Darby canine kidney (MDCK) cells, a polarized epithelial cell line. Using stable retrovirally infected MDCK cells, ZIP8 was shown to localize to the apical rather than basolateral surface; some ZIP8 was also seen inside the cell but outside the nucleus. We found that ZIP8 trafficking is regulated by metal ion availability: ZIP8 is predominantly on the cell surface under conditions of Zn depletion and predominantly within intracellular membranes under conditions of Zn homeostasis. Metal ion regulation of ZIP8 could be critically important in controlling the uptake of Mn 2+and Zn 2+, as well as Cd and perhaps other non-essential metals––from the environment into the animal by way of this symporter on the apical surface of cells.
Dr. Timothy Dalton (Advisor)
39 p.
Health Sciences, Toxicology
Transporter; cadmium; metal toxicity

Recommended Citations

Citations

  • REED, J. M. (2007). CHARACTERIZATION OF THE 8-TRANSMEMBRANE ZIP8 TRANSPORTER: EVIDENCE OF INTRACELLULAR TRAFFICKING IN RESPONSE TO EXTRACELLULAR METAL CONCENTRATIONS [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187007206

    APA Style (7th edition)

  • REED, JODIE. CHARACTERIZATION OF THE 8-TRANSMEMBRANE ZIP8 TRANSPORTER: EVIDENCE OF INTRACELLULAR TRAFFICKING IN RESPONSE TO EXTRACELLULAR METAL CONCENTRATIONS. 2007. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187007206.

    MLA Style (8th edition)

  • REED, JODIE. "CHARACTERIZATION OF THE 8-TRANSMEMBRANE ZIP8 TRANSPORTER: EVIDENCE OF INTRACELLULAR TRAFFICKING IN RESPONSE TO EXTRACELLULAR METAL CONCENTRATIONS." Master's thesis, University of Cincinnati, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1187007206

    Chicago Manual of Style (17th edition)

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© 2007, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.