Linked Life Data

20734416

Source:http://linkedlifedata.com/resource/pubmed/id/20734416

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2010-9-21
pubmed:abstractText
Numerous epidemiological studies suggest that the expression of the HFE allelic variant H63D may be a risk factor or genetic modifier for Alzheimer's disease (AD). The H63D variant alters cellular iron homeostasis and increases baseline oxidative stress. The elevated cellular stress milieu, we have proposed, may alter cellular responses to genetic and environmental determinants of AD. Accumulation of ?-amyloid peptides (A?) is one of the most prominent pathogenic characteristics of AD. Several studies have demonstrated that A? can induce neuronal cell death through apoptosis. In this study, we provide evidence that an A?(25-35) fragment, which contains the cytotoxic sequence of the amyloid peptide, activates the intrinsic apoptotic pathway in SH-SY5Y human neuroblastoma cells expressing the HFE allelic variant H63D to a greater extent than in cells with wild-type (WT) HFE. Specifically, A?(25-35) peptide exposure significantly induced Bax translocation from the cytosol to the mitochondria in H63D-expressing cells compared with WT cells. This translocation was associated with increased cytochrome c release from mitochondria and an increase in active caspase-9 and caspase-3 activity in H63D cells. Consequently, there is increased apoptosis in cells expressing the H63D variant as opposed to cells expressing WT HFE. We also found increased amyloid precursor protein (APP) and A?(1-42) peptide in the mitochondrial compartment as well as increased mitochondrial stress in H63D-expressing cells compared with WT. These findings support our hypothesis that the presence of the HFE H63D allele enables factors that trigger neurodegenerative processes associated with AD and predisposes cells to cytotoxcity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1097-4547
pubmed:author
pubmed:copyrightInfo
© 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3079-89
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
The H63D HFE gene variant promotes activation of the intrinsic apoptotic pathway via mitochondria dysfunction following ?-amyloid peptide exposure.
pubmed:affiliation
Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Pathumwan, Bangkok, Thailand.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't