Glucose-induced regulation of novel iron transporters in vascular endothelial cell dysfunction

Increased iron indices have been associated with the development of diabetes and its complications. In the present study, we have investigated the glucose-induced alteration of iron transporters, divalent metal transporter-1 (DMT-1), iron regulated transporter protein-1 (IREG-1), and transferrin rec...

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Bibliographic Details
Published in:Free radical research 2005-11, Vol.39 (11), p.1203-1210
Main Authors: Khan, Zia A., Farhangkhoee, Hana, Barbin, Yousef P., Adams, Paul C., Chakrabarti, Subrata
Format: Article
Language:English
Subjects:
Biological Transport
Blotting, Western
Cation Transport Proteins - metabolism
Cells, Cultured
diabetes
DNA, Complementary - metabolism
Endothelium, Vascular - cytology
Endothelium, Vascular - pathology
Gene Expression Regulation
Glucose - metabolism
Humans
Immunoblotting
Immunohistochemistry
Iron
Iron - metabolism
Iron-Binding Proteins - metabolism
Models, Biological
Oxidative Stress
Receptors, Transferrin - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA - metabolism
RNA, Messenger - metabolism
Up-Regulation
vasculopathy
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Summary:Increased iron indices have been associated with the development of diabetes and its complications. In the present study, we have investigated the glucose-induced alteration of iron transporters, divalent metal transporter-1 (DMT-1), iron regulated transporter protein-1 (IREG-1), and transferrin receptor (TfR), in endothelial cell iron accumulation and oxidative stress. Cells were exposed to high glucose levels and subjected to gene expression, protein expression, iron measurement and assessment of oxidative stress. Our results show, for the first time, expression of DMT-1 and IREG-1 in vascular endothelial cells. Our data further indicates upregulation of DMT-1 and IREG-1 mRNA and protein in response to high levels of glucose. TfR, however, exhibited a modest decrease in response to high levels of glucose. Increased expression of DMT-1 and IREG-1 was associated with iron accumulation and oxidative stress. Furthermore, our results show differential expression of iron transporters with treatment of high glucose-exposed cells with two different iron chelators. In conclusion, our study suggests that glucose-induced alteration of iron transporters may arbitrate iron accumulation and oxidative stress in endothelial cells.
ISSN:1071-5762
1029-2470
DOI:10.1080/10715760500143254