Expression and localization of duodenal cytochrome b in the rat hippocampus after kainate-induced excitotoxicity
Autor: | Hwa-Young Kim, Sau Yeen Loke, Abdullah S. Alhomida, Wei-Yi Ong, Nikhat J. Siddiqi |
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Rok vydání: | 2013 |
Předmět: |
Male
Excitotoxicity medicine.disease_cause Hippocampus Ferrous Duodenal cytochrome B Excitatory Amino Acid Agonists medicine Animals Rats Wistar Kainic Acid Glial fibrillary acidic protein biology Chemistry General Neuroscience Glutamate receptor DMT1 Cytochrome b Group Molecular biology Rats medicine.anatomical_structure Gene Expression Regulation biology.protein Ferric Oxidoreductases medicine.drug Astrocyte |
Zdroj: | Neuroscience. 245:179-190 |
ISSN: | 0306-4522 |
Popis: | Brain iron accumulation and oxidative stress are common features of many neurodegenerative diseases, and could be due in part to increased iron influx across the blood-brain interface. The iron transport protein, divalent metal transporter 1 (DMT1) is found in reactive astrocytes of the lesioned hippocampal CA fields after excitotoxicity induced by the glutamate analog kainate (KA), but in order for iron to be transported by DMT1, it must be converted from the ferric to the ferrous form. The present study was carried out to investigate the expression of a ferric reductase, duodenal cytochrome b (DCYTB), in the rat hippocampus after KA injury. Quantitative reverse transcriptase-polymerase chain reaction showed significant increases in DCYTB mRNA expression of 2.5, 2.7, and 5.2-fold in the hippocampus at 1week, 2weeks and 1month post-KA lesions respectively compared to untreated controls, and 3.0-fold compared to 1month post-saline injection. DCYTB-positive cells were double labeled with glial fibrillary acidic protein, and electron microscopy showed that the DCYTB-positive cells had dense bundles of glial filaments, characteristic of astrocytes, and were present as end-feet around unlabeled brain capillary endothelial cells. DMT1 labeling in astrocytes and increased iron staining were also observed in the lesioned hippocampus. Together, the present findings of DCYTB and DMT1 localization in astrocytes suggest that DCYTB is a ferric reductase for reduction of ferric iron, for transport by DMT1 into the brain. We postulate that the coordinated action of these two proteins could be important in iron influx across the blood-brain interface, in areas undergoing neurodegeneration. |
Databáze: | OpenAIRE |
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