Toxicity of various amyloid ? peptide species in cultured human blood-brain barrier endothelial cells: Increased toxicity of Dutch-type mutant

Gln(22), which is the major species deposited in the cerebrovascular blood vessels of victims of hereditary cerebral hemorrhage with amyloidosis, Dutch type. We find that aggregates of both peptides, as well as of A beta(1-42) and A beta(25-35), are toxic to cultured human cerebrovascular endothelial cells (hBEC) obtained from the brain of a victim of AD (at doses lower than those that are toxic to CNS neurons or leptomeningeal smooth muscle cells). Soluble A beta(1-40) Gln(22) is equally toxic to hBEC, whereas wild-type A beta(1-40) is toxic only at higher doses. This toxicity is seen at the lowest dose of A beta(1-40) Gln (22) used, 20 nM. The soluble A beta(1-40)Gln(22) aggregates on the surface of the cells, in contrast to A beta(1-40), and its toxicity can be blocked both by an inhibitor of free radical formation and by Congo red, which inhibits amyloid fibril formation. We discuss the possibility that the enhanced toxicity of A beta(1-40)Gln(22) is mediated by a A beta receptor on the endothelial cells. -->
ISSN: 1097-4547
0360-4012
DOI: 10.1002/1097-4547(20000615)60:6<804::aid-jnr13>3.0.co;2-1
Přístupová URL adresa: https://explore.openaire.eu/search/publication?articleId=doi_________::a729b51f34c13a9dde00e992c4eda6a5
https://doi.org/10.1002/1097-4547(20000615)60:6<804::aid-jnr13>3.0.co;2-1
Rights: CLOSED
Přírůstkové číslo: edsair.doi...........a729b51f34c13a9dde00e992c4eda6a5
Autor: Patricia B. Eisenhauer, Richard E. Fine, Theresa A. Davies, John M. Wells, Robin J. Johnson
Rok vydání: 2000
Předmět:
Zdroj: Journal of Neuroscience Research. 60:804-810
ISSN: 1097-4547
0360-4012
DOI: 10.1002/1097-4547(20000615)60:6<804::aid-jnr13>3.0.co;2-1
Popis: The amyloid beta peptide (A beta) is the major component of the neuritic and cerebrovascular amyloid plaques that are one of the characteristic features of Alzheimer's disease (AD). This peptide has been shown to be toxic to several relevant cell types, including neurons, cerebrovascular smooth muscle cells, and endothelial cells. We have studied the toxic effects of both soluble and aggregated species of A beta(1-40) and the mutation A beta(1-40)Glu-->Gln(22), which is the major species deposited in the cerebrovascular blood vessels of victims of hereditary cerebral hemorrhage with amyloidosis, Dutch type. We find that aggregates of both peptides, as well as of A beta(1-42) and A beta(25-35), are toxic to cultured human cerebrovascular endothelial cells (hBEC) obtained from the brain of a victim of AD (at doses lower than those that are toxic to CNS neurons or leptomeningeal smooth muscle cells). Soluble A beta(1-40) Gln(22) is equally toxic to hBEC, whereas wild-type A beta(1-40) is toxic only at higher doses. This toxicity is seen at the lowest dose of A beta(1-40) Gln (22) used, 20 nM. The soluble A beta(1-40)Gln(22) aggregates on the surface of the cells, in contrast to A beta(1-40), and its toxicity can be blocked both by an inhibitor of free radical formation and by Congo red, which inhibits amyloid fibril formation. We discuss the possibility that the enhanced toxicity of A beta(1-40)Gln(22) is mediated by a A beta receptor on the endothelial cells.
Databáze: OpenAIRE
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