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Zinc enhances synthesis of presenilin 1 in mouse primary cortical culture.

Authors
Park, IH; Jung, MW; Mori, H; Mook-Jung, I
Citation
Biochemical and biophysical research communications, 285(3):680-688, 2001
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
Whether zinc interacts with presenilin 1 (PS1), one of the causative genes of familial Alzheimer's disease (AD), is not known. Here we report that zinc modulates the synthesis of PS1. Exogenous zinc enhanced the amount of C-terminal fragments of PS1 (PS1-CTF) in neonatal mouse cortical cultures in a dose-dependent manner. Zinc also induced cell death in a dose-dependent manner. These effects of zinc were not mimicked by calcium, copper, or iron, and were blocked by a zinc-specific chelator, TPEN. Experiments using metabolic labeling and cycloheximide treatment revealed that zinc increased PS1-CTF by elevating the de novo synthesis of PS1. Time course experiments revealed that cell death commenced sooner (0.5-1 h) than enhancement of PS1-CTF (1-2 h) following zinc treatment. However, the amount of PS1-CTF remained unchanged during etoposide- or H(2)O(2)-induced cell death, suggesting that enhancement of PS1 synthesis is specifically correlated with zinc-induced cell death.
MeSH terms
Alzheimer Disease/metabolismAnimalsCalcium Chloride/pharmacologyCell Death/drug effectsCells, CulturedCerebral Cortex/cytologyCerebral Cortex/drug effects*Cerebral Cortex/metabolism*Chelating Agents/pharmacologyCopper/pharmacologyDose-Response Relationship, DrugEtoposide/pharmacologyFerrous Compounds/pharmacologyHydrogen Peroxide/pharmacologyMembrane Proteins/biosynthesis*MiceMice, Inbred ICRNucleic Acid Synthesis Inhibitors/pharmacologyOxidants/pharmacologyPeptide Fragments/biosynthesisPresenilin-1Zinc/pharmacology*
DOI
10.1006/bbrc.2001.5243
PMID
11453647
Appears in Collections:
Journal Papers > Research Organization > Brain Disease Research Center
Journal Papers > Research Organization > Institute for Medical Sciences
AJOU Authors
박, 인호정, 민환묵, 인희
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