Transferrin receptor-1 suppresses neurite outgrowth in neuroblastoma Neuro2A cells

Yukary Nakamura, Noritaka Nakamichi, Takeshi Takarada, Kiyokazu Ogita, Yukio Yoneda

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 6 days. 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.

Original languageEnglish
Pages (from-to)448-457
Number of pages10
JournalNeurochemistry International
Volume60
Issue number5
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Fingerprint

Transferrin Receptors
Neuroblastoma
Iron
Neurites
Messenger RNA
Transferrin
Tretinoin
Cultured Cells
Cell Membrane
Embryonal Carcinoma Stem Cells
Neurons
Neuronal Outgrowth
Membrane Glycoproteins
Cytotoxins
Eukaryotic Cells
Chelating Agents
Transcriptome
Astrocytes
Small Interfering RNA
Reactive Oxygen Species

Keywords

  • Iron chelator
  • Neurite outgrowth
  • Overexpression
  • siRNA
  • Transferrin receptor-1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Transferrin receptor-1 suppresses neurite outgrowth in neuroblastoma Neuro2A cells. / Nakamura, Yukary; Nakamichi, Noritaka; Takarada, Takeshi; Ogita, Kiyokazu; Yoneda, Yukio.

In: Neurochemistry International, Vol. 60, No. 5, 04.2012, p. 448-457.

Research output: Contribution to journalArticle

Nakamura, Yukary ; Nakamichi, Noritaka ; Takarada, Takeshi ; Ogita, Kiyokazu ; Yoneda, Yukio. / Transferrin receptor-1 suppresses neurite outgrowth in neuroblastoma Neuro2A cells. In: Neurochemistry International. 2012 ; Vol. 60, No. 5. pp. 448-457.
@article{21e85200aaf04dba9c23f5a57ae7d478,
title = "Transferrin receptor-1 suppresses neurite outgrowth in neuroblastoma Neuro2A cells",
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 6 days. 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.",
keywords = "Iron chelator, Neurite outgrowth, Overexpression, siRNA, Transferrin receptor-1",
author = "Yukary Nakamura and Noritaka Nakamichi and Takeshi Takarada and Kiyokazu Ogita and Yukio Yoneda",
year = "2012",
month = "4",
doi = "10.1016/j.neuint.2011.08.018",
language = "English",
volume = "60",
pages = "448--457",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",
number = "5",

}

TY - JOUR

T1 - Transferrin receptor-1 suppresses neurite outgrowth in neuroblastoma Neuro2A cells

AU - Nakamura, Yukary

AU - Nakamichi, Noritaka

AU - Takarada, Takeshi

AU - Ogita, Kiyokazu

AU - Yoneda, Yukio

PY - 2012/4

Y1 - 2012/4

N2 - 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 6 days. 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.

AB - 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 6 days. 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.

KW - Iron chelator

KW - Neurite outgrowth

KW - Overexpression

KW - siRNA

KW - Transferrin receptor-1

UR - http://www.scopus.com/inward/record.url?scp=84857951110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857951110&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2011.08.018

DO - 10.1016/j.neuint.2011.08.018

M3 - Article

C2 - 22019713

AN - SCOPUS:84857951110

VL - 60

SP - 448

EP - 457

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

IS - 5

ER -