Differential effects of zinc on amyloid precursor protein (APP) processing in copper-resistant variants of cultured Chinese hamster ovary cells.
Previous studies have demonstrated that adding copper to Chinese-hamster ovary (CHO) cells greatly reduced the levels of beta-amyloid (Abeta) peptide in parental CHO-K1 and in copper resistant CHO-CUR3 cells which have lower intracellular copper levels. In the current study, zinc, the zinc chelator 1,10-phenanthroline or copper chelators bathocuproine and D-penicillamine were added to the culture media of stably transfected CHO cells. The data show that zinc up to concentrations of 50 microM or the presence of 1,10-phenanthroline specifically increased the level of secreted APP in CHO-K1 cells. By contrast, the level of secreted APP in CHO-CUR3 cells remained unaffected. APP holoprotein increased dramatically in CHO-CUR3 cells compared with CHO-K1 cells. The large decrease of Abeta release seen in both cell lines at elevated extracellular zinc levels was due to specific inhibition of secretion. These results indicate that a disturbed zinc-homeostasis may be an important factor influencing APP production, transport and processing.
Borchardt
T
T
ZMBH-Center for Molecular Biology Heidelberg, University of Heidelberg, Germany.
Schmidt
C
C
Camarkis
J
J
Cappai
R
R
Masters
C L
CL
Beyreuther
K
K
Multhaup
G
G
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004591:Electrophoresis, Polyacrylamide Gel; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008969:Molecular Sequence Data; D010396:Penicillamine / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D011233:Precipitin Tests; D014162:Transfection; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002614:Chelating Agents; D016166:Free Radical Scavengers; D010618:Phenanthrolines; D003300:Copper; C002478:bathocuproine; D007770:L-Lactate Dehydrogenase; D010396:Penicillamine; D015032:Zinc; C025205:1,10-phenanthroline