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Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 2001 Dec 15; Vol. 66 (6), pp. 1198-207. - Publication Year :
- 2001
-
Abstract
- Iron accumulation in the brain occurs in a number of neurodegenerative diseases. Two new iron transport proteins have been identified that may help elucidate the mechanism of abnormal iron accumulation. The Divalent Metal Transporter 1 (DMT1), is responsible for iron uptake from the gut and transport from endosomes. The Metal Transport Protein 1 (MTP1) promotes iron export. In this study we determined the cellular and regional expression of these two transporters in the brains of normal adult and Belgrade rats. Belgrade rats have a defect in DMT1 that is associated with lower levels of iron in the brain. In the normal rat, DMT1 expression is highest in neurons in the striatum, cerebellum, thalamus, ependymal cells lining the third ventricle, and vascular cells throughout the brain. The staining in the ependymal cells and endothelial cells suggests that DMT1 has an important role in iron transport into the brain. In Belgrade rats, there is generalized decrease in immunodetectable DMT1 compared to normal rats except in the ependymal cells. This decrease in immunoreactivity, however, was absent on immunoblots. The immunoblot analysis indicates that this protein did not upregulate to compensate for the chronic defect in iron transport. MTP1 staining is found in most brain regions. MTP1 expression in the brain is robust in pyramidal neurons of the cerebral cortex but is not detected in the vascular endothelial cells and ependymal cells. MTP1 staining in Belgrade rats was decreased compared to normal, but similar to DMT1 this decrease was not corroborated by immunoblotting. These results indicate that DMT1 and MTP1 are involved in brain iron transport and this involvement is regionally and cellularly specific.<br /> (Copyright 2001 Wiley-Liss, Inc.)
- Subjects :
- Animals
Astrocytes cytology
Astrocytes metabolism
Blood Vessels cytology
Blood Vessels metabolism
Blood-Brain Barrier physiology
Brain cytology
Disease Models, Animal
Ependyma cytology
Ependyma metabolism
Heterozygote
Homozygote
Immunohistochemistry
Microcirculation cytology
Microcirculation metabolism
Neurodegenerative Diseases physiopathology
Neurons cytology
Oligodendroglia cytology
Oligodendroglia metabolism
Rats
Rats, Mutant Strains
Reference Values
Brain metabolism
Brain Chemistry genetics
Cation Transport Proteins metabolism
Iron metabolism
Iron-Binding Proteins
Neurodegenerative Diseases metabolism
Neurons metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0360-4012
- Volume :
- 66
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 11746453
- Full Text :
- https://doi.org/10.1002/jnr.1256