ACLS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yamauchi, K.
Right arrow Articles by Katsuyama, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yamauchi, K.
Right arrow Articles by Katsuyama, T.
Annals of Clinical & Laboratory Science 33:68-78 (2003)
© 2003 Association of Clinical Scientists

Internalization of ß-Amyloid Causes Downregulation of Apolipoprotein E mRNA Expression in Neuroblastoma Cells

Kazuyoshi Yamauchi, Minoru Tozuka, Eiko Hidaka, Ichiro Ueno, Kazuyuki Matsuda and Tsutomu Katsuyama
Department of Laboratory Medicine, Shinshu University Hospital and Medical School, Matsumoto, Japan

Address correspondence to Kazuyoshi Yamauchi, Ph.D., Department of Laboratory Medicine, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan; tel 81 263 37 2802; fax 81 263 34 5316; e-mail yamauchi{at}hsp.md.shinshu-u.ac.jp.

Apolipoprotein (apo) E, like ß-amyloid (Aß), is a key component of the senile plaques that characterize Alzheimer’s disease (AD). Understanding how apoE participates in the formation of senile plaques is necessary to clarify the pathogenesis of AD; however, the mechanism remains unknown. In this study, we investigated the changes of cellular apoE and its mRNA level induced by addition of extracellular Aß to neuroblastoma cells. The presence of >=1.0 µmol/L of Aß induced a decrease of apoE mRNA expression and an increase in the immunofluorescence reactivity for intracellular apoE. Both Aß and apoE were observed by electron-microscopy to be localized within lysosomes. The levels of intracellular apoE and its mRNA returned to the steady state time-dependently. These changes were attenuated by treatments with heparinase I or receptor-associated protein. These findings suggest that the internalized Aß, along with cellular apoE, induces downregulation of apoE mRNA via a pathway possibly mediated by apoE receptors and heparin sulfate proteoglycans. A disorder of this physiological response could be linked to the development of AD.

Keywords: Alzheimer’s disease, apoE, LRP, RT-PCR, electron microscopy, neuroblastoma cells

Abbreviations: Aß, ß-amyloid; apo, apolipoprotein; AD, Alzheimer’s disease; CNS, central nervous system; LDL, low density lipoprotein; VLDL, very low density lipoprotein; LRP, LDL receptor-related protein; APP, amyloid precursor protein; RAP, receptor-associated protein; RT, reverse transcription; PCR, polymerase chain reaction; FITC, fluorescein isothiocyanate; FCS, fetal calf serum; DMSO, dimethylsulfoxide; DEPC, diethylpyrocarbonate; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; DAB, diaminobenzidine






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the Association of Clinical Scientists.