Transferrin receptor-1 suppresses neurite outgrowth in neuroblastoma Neuro2A cells |
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Authors: | Nakamura Yukary Nakamichi Noritaka Takarada Takeshi Ogita Kiyokazu Yoneda Yukio |
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Institution: | Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences, Kanazawa University Graduate School of Natural Science and Technology, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan. |
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Abstract: | Transferrin receptor-1 (TfR1) is a cell membrane-associated glycoprotein responsible for incorporation of the iron bound to transferrin through an endocytotic process from the circulating blood. Iron is believed to play a dual role as an active center of the electron transfer system in mitochondria and as an endogenous cytotoxin through promoted generation of reactive oxygen species in different eukaryotic cells. In this study, we evaluated expression profiles of different genes related to iron mobilization across plasma membranes in neuronal cells. Marked mRNA expression was seen for various iron-related genes such as TfR1 in cultured mouse neocortical neurons, while TfR1 mRNA levels were more than doubled during culture from 3 to 6days. In mouse embryonal carcinoma P19 cells endowed to differentiate into neuronal and astroglial lineages, a transient increase was seen in both mRNA and corresponding protein for TfR1 in association with neuronal marker expression during culture with all-trans retinoic acid (ATRA). In neuronal Neuro2A cells cultured with ATRA, moreover, neurite was elongated together with increased expression of both mRNA and protein for TfR1. Overexpression of TfR1 significantly decreased the length of neurite elongated, however, while significant promotion was invariably seen in the neurite elongation in Neuro2A cells transfected with TfR1 siRNA as well as in Neuro2A cells cultured with an iron chelator. These results suggest that TfR1 would be highly expressed by neurons rather than astroglia to play a negative role in the neurite outgrowth after the incorporation of circulating transferrin in the brain. |
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Keywords: | α-MEM alpha modified minimum essential medium apo-Tf apo-transferrin ATRA all-trans retinoic acid Dcytb duodenal cytochrome-b DFO deferoxamine DIV days in vitro DMEM Dulbecco’s modified Eagle’s medium DMT1 divalent metal transporter-1 FBS fetal bovine serum ferritin-H ferritin-heavy chain ferritin-L ferritin-light chain GAPDH glyceraldehydes-3-phosphate dehydrogenase GFAP glial fibrillary acidic protein GFP green fluorescent protein IRP1 iron regulatory protein-1 MAP2 microtubules-associated protein-2 PBS phosphate-buffered saline ROS reactive oxygen species STEAP3 six-transmembrane epithelial antigen of the prostate-3 Tf transferrin TfR1 transferrin receptor-1 ZIP14 zinc-regulated transporter/iron-regulated transporter-like protein-14 ZRT zinc-regulated transporter |
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