Zinc enhances synthesis of presenilin 1 in mouse primary cortical culture.
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.
Park
I H
IH
Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea 442-721.
Jung
M W
MW
Mori
H
H
Mook-Jung
I
I
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D010446:Peptide Fragments / Q000096:biosynthesis; D053764:Presenilin-1; D015032:Zinc / Q000494:pharmacology*
D002614:Chelating Agents; D005296:Ferrous Compounds; D008565:Membrane Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D016877:Oxidants; D010446:Peptide Fragments; D053764:Presenilin-1; D005047:Etoposide; D003300:Copper; D006861:Hydrogen Peroxide; D015032:Zinc; D002122:Calcium Chloride; C029892:cupric chloride; C029451:ferrous chloride