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Zinc Inhibits Amyloid beta Production from Alzheimer's Amyloid Precursor Protein in SH-SY5Y Cells

Authors
 Jinu Lee  ;  Chul Hoon Kim  ;  Dong Goo Kim  ;  Young Soo Ahn 
Citation
 KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, Vol.13(3) : 195-200, 2009 
Journal Title
 KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY 
ISSN
 1226-4512 
Issue Date
2009
Keywords
Amyloid beta ; Amyloid precursor protein ; Pyrrolidine dithiocarbamate ; Zinc
Abstract
Zinc released from excited glutamatergic neurons accelerates amyloid beta (Abeta) aggregation, underscoring the therapeutic potential of zinc chelation for the treatment of Alzheimer's disease (AD). Zinc can also alter Abeta concentration by affecting its degradation. In order to elucidate the possible role of zinc influx in secretase-processed Abeta production, SH-SY5Y cells stably expressing amyloid precursor protein (APP) were treated with pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, and the resultant changes in APP processing were examined. PDTC decreased Abeta40 and Abeta42 concentrations in culture media bathing APP-expressing SH-SY5Y cells. Measuring the levels of a series of C-terminal APP fragments generated by enzymatic cutting at different APP-cleavage sites showed that both beta- and alpha-cleavage of APP were inhibited by zinc influx. PDTC also interfered with the maturation of APP. PDTC, however, paradoxically increased the intracellular levels of Abeta40. These results indicate that inhibition of secretase-mediated APP cleavage accounts -at least in part- for zinc inhibition of Abeta secretion.
Files in This Item:
T200902186.pdf Download
DOI
10.4196/kjpp.2009.13.3.195
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dong Goo(김동구)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Ahn, Young Soo(안영수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/104063
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