Endothelin-converting enzyme-1 in Alzheimer's disease and vascular dementia.
Neuropathol Appl Neurobiol
; 36(6): 487-97, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-20345647
ABSTRACT
AIMS:
Alzheimer's disease (AD) is believed to be caused by the accumulation of amyloid beta (Aß) peptide within the brain. Endothelin-converting enzyme-1 and 2 (ECE-1 and ECE-2) are expressed in endothelial cells and neurones, respectively, and both cleave 'big endothelin' to produce the vasoconstrictor endothelin-1 (ET-1). ECE-1 and ECE-2 also degrade Aß. AD patients have regionally reduced microvascular blood flow in the brain, with impaired endothelium-dependent relaxation and cerebrovascular autoregulation, and abnormal production of ET-1 has been demonstrated in mice overexpressing amyloid precursor protein. We recently found ECE-2 mRNA and protein to be elevated in the brain in AD. In vitro, expression of ECE-2 was upregulated by Aß. Our aims for this study were to examine expression of ECE-1 (which has 57% homology with ECE-2) in temporal cortex from patients with AD, vascular dementia (VaD) and controls.METHODS:
We examined the distribution of ECE-1 with immunohistochemistry, and measured ECE-1 mRNA by real-time polymerase chain reaction (PCR). ECE-1 protein levels were measured by western blot, and results analysed before and after adjustment for factor VIII-related antigen.RESULTS:
We showed ECE-1 to be in vascular endothelial cells. We did not find significant differences in ECE-1 mRNA or protein levels (either full-length ECE-1 or the soluble spliced variant, ECE-1sv) in AD or VaD compared with controls.CONCLUSIONS:
Our findings suggest that any disease-specific contribution of ECE-1 to the accumulation of Aß or reduction in local microvascular blood flow in AD or VaD is probably small, with abnormal production of ET-1 being more likely to reflect Aß-mediated upregulation of ECE-2.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metaloendopeptidases
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Demência Vascular
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Biomarcadores Tumorais
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Ácido Aspártico Endopeptidases
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Doença de Alzheimer
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article