ECE1
Endothelin-converting enzyme 1 (EC 3.4.24.71) (ECE-1)
PublicationsПравить
It is well known that oxidative stresses induce the production of amyloid [i]β[/i] (A[i]β[/i]) in the brain, lens, and retina, leading to age-related diseases. In the present study, we investigated the effects of ferulic acid on the A[i]β[/i] levels in H O -stimulated human lens epithelial (HLE) SRA 01/04 cells. Three types of A[i]β[/i] peptides (A[i]β[/i] , A[i]β[/i] , and A[i]β[/i] ) were measured by ELISA, and the levels of mRNA for the expressed proteins related to A[i]β[/i] production (APP, BACE1, and PS proteins) and degradation (ADAM10, NEP, and ECE1 proteins) were determined by quantitative real-time RT-PCR. H O stimulation augmented gene expression of the proteins related to A[i]β[/i] production, resulting in the production of three types of A[i]β[/i] peptides. Treatment with 0.1 [i]μ[/i]M ferulic acid attenuated the augmentations of gene expression and production of the proteins related to the secretion of three types of A[i]β[/i] peptides in the H O -stimulated HLE cells. These results provided evidence of antioxidative functions of ferulic acid for lens epithelial cells.
MeSH Terms
- Aging
- Amyloid beta-Peptides
- Antioxidants
- Cell Line
- Coumaric Acids
- Epithelial Cells
- Gene Expression Regulation
- Humans
- Hydrogen Peroxide
- Macular Degeneration
- Oxidative Stress
The β-amyloid peptide may play a central role in Alzheimer's disease (AD) pathogenesis. We have evaluated variants in seven Aβ-degrading genes (ACE, ECE1, ECE2, IDE, MME, PLAU, and TF) for association with AD risk in the Genetic and Environmental Risk in Alzheimer's Disease Consortium 1 (GERAD1) cohort, and with three cognitive phenotypes in the Lothian Birth Cohort 1936 (LBC1936), using 128 and 121 SNPs, respectively. In GERAD1, we identified a significant association between a four-SNP intragenic ECE1 haplotype and risk of AD in individuals that carried at least one APOE ε4 allele (P = 0.00035, odds ratio = 1.61). In LBC1936, we identified a significant association between a different two-SNP ECE1 intragenic haplotype and non-verbal reasoning in individuals lacking the APOE ε4 allele (P = 0.00036, β = -0.19). Both results showed a trend towards significance after permutation (0.05 < P < 0.10). A follow-up cognitive genetic study evaluated the association of ECE1 SNPs in three additional cohorts of non-demented older people. Meta-analysis of the four cohorts identified the significant association (Z < 0.05) of SNPs in the ECE-1b promoter with non-verbal reasoning scores, particularly in individuals lacking the APOE ε4 allele. Our genetic findings are not wholly consistent. Nonetheless, the AD associated intronic haplotype is linked to the 338A variant of known ECE1b promoter variant, 338C>A (rs213045). We observed significantly less expression from the 338A variant in two human neuroblastoma cell lines and speculate that this promoter may be subject to tissue-specific regulation.
MeSH Terms
- Aged
- Aging
- Alzheimer Disease
- Amyloid beta-Peptides
- Aspartic Acid Endopeptidases
- Cognition
- Cohort Studies
- Endothelin-Converting Enzymes
- Female
- Genetic Predisposition to Disease
- Humans
- Male
- Meta-Analysis as Topic
- Metalloendopeptidases
- Middle Aged
- Neuropsychological Tests
- Phenotype
- Polymorphism, Single Nucleotide
- Promoter Regions, Genetic
- Proteolysis
- Risk Factors