Protective effect of zinc on amyloid-beta 25-35 and 1-40 mediated toxicity.
Amyloid beta-peptide (Abeta) is widely held to be associated with Alzheimer's disease, the insoluble aggregates of the peptide being the major constituents of senile plaques. In this study, we evaluated the effect of Zn(2+) (5, 50 and 200 microM) on Abeta induced toxicity using the human teratocarcinome (NT2) cell line. Our results proved that 50 and 200 microM Zn(2+) protected NT2 cells from Abeta 25-35 toxicity. Zinc was also shown to be effective by preventing the loss of mitochondrial membrane potential (DeltaPsi(m)) induced by Abeta 25-35, not allowing cytochrome c release from mitochondria, and subsequently, caspase 3 activation. However, when the cells were treated with Abeta 1-40, only Zn(2+) 5 microM had a protective effect. We have further observed that 5 microM Zn(2+) prevented Abeta 1-40 aggregation into a beta-sheet structure. Considering the results presented, we argue that Zn(2+) has a concentration-dependent protective effect.
Cardoso
S M
SM
Center for Neuroscience and Cellular Biology of Coimbra and Institute of Biochemistry, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Rego
A C
AC
Pereira
C
C
Oliveira
C R
CR
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004396:Coloring Agents; D003224:Congo Red; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000187:drug effects; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity*; D017433:Protein Structure, Secondary / Q000187:drug effects; D013844:Thiazoles; D015032:Zinc / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D004396:Coloring Agents; D009498:Neurotoxins; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); C009462:thioflavin T; D003224:Congo Red; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015032:Zinc