Linked Life Data

15537749

Source:http://linkedlifedata.com/resource/pubmed/id/15537749

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-1-5
pubmed:abstractText
Aluminum maltolate (Al-malt) causes neurodegeneration following in vivo exposure, and apoptosis plays a prominent role. The objective of this study was to define the form of cell death induced by Al-malt and to establish an in vitro model system amenable to mechanistic investigations of Al-malt-induced cell death. Neuro-2a cells, a murine neuroblastoma cell line, were treated with Al-malt for 24 h, following which mode of cell death and alterations in apoptosis-related gene expression were studied. Al-malt concentration-dependently increased cell death. The mode of cell death was a combination of apoptosis and necrosis. Treatment with Al-malt resulted in caspase 3 activation and the externalization of phosphatidyl serine, both indicative of apoptosis. In addition, nuclear condensation and fragmentation were evident. Interestingly, pretreatment with cycloheximide (CHX), a potent protein synthesis inhibitor markedly reduced Al-malt-induced apoptosis, indicating that altered gene expression was critical for this form of cell death. Pretreatment with CHX had no effect on necrosis induced by Al-malt. Analysis of gene expression showed that p53 mRNA was increased following treatment with Al-malt. This increase was accompanied by a marked inhibition of Bcl2 expression and an increase in BAX expression, a pattern of gene expression suggestive of a pro-apoptotic shift. Results show for the first time that p53 is induced by Al in neuron-like cells and suggest that the p53-dependent intrinsic pathway may be responsible for Al-induced apoptosis. Future studies investigating the role of p53 in Al neurotoxicity both in vivo and in vitro are warranted.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-39
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:15537749-Aluminum, pubmed-meshheading:15537749-Animals, pubmed-meshheading:15537749-Apoptosis, pubmed-meshheading:15537749-Cell Line, Tumor, pubmed-meshheading:15537749-Cell Survival, pubmed-meshheading:15537749-Dose-Response Relationship, Drug, pubmed-meshheading:15537749-Gene Expression, pubmed-meshheading:15537749-Genes, p53, pubmed-meshheading:15537749-Mice, pubmed-meshheading:15537749-Necrosis, pubmed-meshheading:15537749-Neuroblastoma, pubmed-meshheading:15537749-Organometallic Compounds, pubmed-meshheading:15537749-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:15537749-Pyrones, pubmed-meshheading:15537749-RNA, Messenger, pubmed-meshheading:15537749-Signal Transduction, pubmed-meshheading:15537749-Tumor Suppressor Protein p53, pubmed-meshheading:15537749-bcl-2-Associated X Protein
pubmed:year
2005
pubmed:articleTitle
Aluminum-maltolate induces apoptosis and necrosis in neuro-2a cells: potential role for p53 signaling.
pubmed:affiliation
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, Georgia 30602, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't