Abstract
Multiple aspects of homocysteine metabolism were studied to understand the mechanism responsible for hyperhomocysteinemia toxicity in Alzheimer disease. Besides oxidative stress and vascular damage, homocysteine has also a great importance in regulating DNA methylation through S-adenosylmethionine, the main methyl donor in eukaryotes. Alterations of S-adenosylmethionine and methylation were evidenced in Alzheimer disease and in elderly. In order to clarify whether DNA methylation can provide the basis for amyloid-beta overproduction, we used human SK-N-BE neuroblastoma and A172 glioblastoma cell lines. We tested the effects of folate, B12 and B6 deprivation and S-adenosylmethionine addition on methylation metabolism. Our results indicate that homocysteine accumulation induced through vitamin B deprivation could impair the "Methylation Potential" with consequent presenilin 1, BACE and amyloid-beta upregulation. Moreover, we found that homocysteine alterations had an effect on neuroblastoma but not on glioblastoma cells; this suggests a possible differential role of the two cell types in Alzheimer disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Alzheimer Disease / genetics
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Amyloid Precursor Protein Secretases / genetics
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Amyloid Precursor Protein Secretases / metabolism*
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Amyloid beta-Protein Precursor / metabolism
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Antioxidants / administration & dosage
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Antioxidants / pharmacology
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Aspartic Acid Endopeptidases / genetics
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Aspartic Acid Endopeptidases / metabolism
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Blotting, Western
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Cell Line, Tumor / pathology
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DNA Methylation / drug effects
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DNA Primers / genetics
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Folic Acid / administration & dosage
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Folic Acid / pharmacology
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Glioblastoma / metabolism*
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Glioblastoma / pathology*
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Homocysteine / metabolism*
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Humans
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Neuroblastoma / metabolism*
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Neuroblastoma / pathology*
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Oxidative Stress / physiology
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Polymerase Chain Reaction
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Presenilin-1 / genetics
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Presenilin-1 / metabolism
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S-Adenosylmethionine / administration & dosage
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S-Adenosylmethionine / pharmacology
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Up-Regulation
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Vitamin B 12 Deficiency / metabolism
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Vitamin B 6 Deficiency / metabolism
Substances
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Amyloid beta-Protein Precursor
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Antioxidants
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DNA Primers
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Presenilin-1
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Homocysteine
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S-Adenosylmethionine
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Folic Acid
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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BACE1 protein, human