TY - JOUR
T1 - Stoichiometries of transferrin receptors 1 and 2 in human liver
AU - Chloupková, Maja
AU - Zhang, An Sheng
AU - Enns, Caroline A.
N1 - Funding Information:
We thank to Kristin Diez-Sauter, Tul-Dim Cing, and Dara Partovi for technical assistance. We are also grateful to Katarina Luciakova, Juxing Chen, Junwei Gao, Julia Maxson and Kristina Nicholson for critical reading of the manuscript. This work was supported by National Institutes of Health Grants DK072166 and DK54488 (to C.A.E.) and in part by Medical Research Foundation of Oregon ACEBD0082 (to M.C.).
PY - 2010/1
Y1 - 2010/1
N2 - Mutations in either the hereditary hemochromatosis protein, HFE, or transferrin receptor 2, TfR2, result in a similarly severe form of the most common type of iron overload disease called hereditary hemochromatosis. Models of the interactions between HFE, TfR1, and TfR2 imply that these proteins are present in different molar concentrations in the liver, where they control expression of the iron regulatory hormone, hepcidin, in response to body iron loading. The aim of this study was to determine in vivo levels of mRNA by quantitative RT-PCR and concentrations of these proteins by quantitative immunoblotting in human liver tissues. The level of TfR2 mRNA was 21- and 63-fold higher than that of TfR1 and HFE, respectively. Molar concentration of TfR2 protein was the highest and determined to be 1.95 nmol/g protein in whole cell lysates and 10.89 nmol/g protein in microsomal membranes. Molar concentration of TfR1 protein was 4.5- and 6.1-fold lower than that of TfR2 in whole cell lysates and membranes, respectively. The level of HFE protein was below 0.53 nmol/g of total protein. HFE is thus present in substoichiometric concentrations with respect to both TfR1 and TfR2 in human liver tissue. This finding supports a model, in which availability of HFE is limiting for formation of complexes with TfR1 or TfR2.
AB - Mutations in either the hereditary hemochromatosis protein, HFE, or transferrin receptor 2, TfR2, result in a similarly severe form of the most common type of iron overload disease called hereditary hemochromatosis. Models of the interactions between HFE, TfR1, and TfR2 imply that these proteins are present in different molar concentrations in the liver, where they control expression of the iron regulatory hormone, hepcidin, in response to body iron loading. The aim of this study was to determine in vivo levels of mRNA by quantitative RT-PCR and concentrations of these proteins by quantitative immunoblotting in human liver tissues. The level of TfR2 mRNA was 21- and 63-fold higher than that of TfR1 and HFE, respectively. Molar concentration of TfR2 protein was the highest and determined to be 1.95 nmol/g protein in whole cell lysates and 10.89 nmol/g protein in microsomal membranes. Molar concentration of TfR1 protein was 4.5- and 6.1-fold lower than that of TfR2 in whole cell lysates and membranes, respectively. The level of HFE protein was below 0.53 nmol/g of total protein. HFE is thus present in substoichiometric concentrations with respect to both TfR1 and TfR2 in human liver tissue. This finding supports a model, in which availability of HFE is limiting for formation of complexes with TfR1 or TfR2.
KW - HFE
KW - Hereditary hemochromatosis
KW - Human liver
KW - TfR1
KW - TfR2
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U2 - 10.1016/j.bcmd.2009.09.004
DO - 10.1016/j.bcmd.2009.09.004
M3 - Article
C2 - 19819738
AN - SCOPUS:72649093389
SN - 1079-9796
VL - 44
SP - 28
EP - 33
JO - Blood Cells, Molecules, and Diseases
JF - Blood Cells, Molecules, and Diseases
IS - 1
ER -