Robert Cousins

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New insights into mammalian zinc metabolism have been acquired through the identification and characterization of zinc transporters. These proteins all have transmembrane domains, and are encoded by two solute-linked carrier (SLC) gene families: ZnT (SLC30) and Zip (SLC39). There are at least 9 ZnT and 15 Zip transporters in human cells. They appear to have(More)
Structural, catalytic, and regulatory functions of zinc in biology continue to be defined. The number of genes coding for proteins with zinc-binding domains is conservatively estimated at 3% of the human genome but possibly is asmuch as 10% (1, 2). Zinc utilization in abundant, yet diverse, applications illustrateswhy organisms have evolved specific(More)
Research advances defining how zinc is transported into and out of cells and organelles have increased exponentially within the past five years. Research has progressed through application of molecular techniques including genomic analysis, cell transfection, RNA interference, kinetic analysis of ion transport, and application of cell and animal models(More)
The zinc transporter ZIP8 is highly expressed in T cells derived from human subjects. T cell ZIP8 expression was markedly up-regulated upon in vitro activation. T cells collected from human subjects who had received oral zinc supplementation (15 mg/day) had higher expression of the activation marker IFN-gamma upon in vitro activation, indicating a(More)
Infection and inflammation produce systemic responses that include hypozincemia and hypoferremia. The latter involves regulation of the iron transporter ferroportin 1 by hepcidin. The mechanism of reduced plasma zinc is not known. Transcripts of the two zinc transporter gene families (ZnT and Zip) were screened for regulation in mouse liver after(More)
Zip14 is a member of the SLC39A zinc transporter family, which is involved in zinc uptake by cells. Up-regulation of Zip14 by IL-6 appears to contribute to the hepatic zinc accumulation and hypozincemia of inflammation. At least three members of the SLC39A family transport other trace elements, such as iron and manganese, in addition to zinc. We analyzed(More)
The regulation of cellular zinc uptake is a key process in the overall mechanism governing mammalian zinc homeostasis and how zinc participates in cellular functions. We analyzed the zinc transporters of the Zip family in both the brain and liver of zinc-deficient animals and found a large, significant increase in Zip10 expression. Additionally, Zip10(More)
In view of evidence that Zn(2+) neurotoxicity contributes to some forms of pathological neuronal death, we developed a model of Zn(2+) neurotoxicity in a cell line amenable to genetic manipulations. Exposure to 500 microM ZnCl(2) for 15 min under depolarizing conditions resulted in modest levels of PC12 cell death, that was reduced by the L-type Ca(2+)(More)
An effective measure to assess zinc status of humans has remained elusive, in contrast to iron, where a number of indicators of metabolism/function are available. Using monocytes, T lymphocytes, and granulocytes isolated by magnetic sorting and dried blood spots (DBS) derived from 50 mul of peripheral blood, we evaluated the response of metallothionein(More)