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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-4-5
pubmed:abstractText
Mounting evidence suggests that glutamate excitotoxicity induces both enzymatic cleavage and nuclear translocation of apoptosis-inducing factor (AIF), which is involved in apoptosis-like programed cell death characterized by nuclear condensation without appearance of apoptotic bodies. Given the lack of apoptotic bodies in motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis (ALS), the aim of the present study was to determine the role for AIF in this disease. We investigated the expression of AIF in spinal cords obtained at autopsy from ten sporadic ALS patients and ten age-matched, control subjects, using morphological and quantitative techniques. Immunohistochemical analysis showed that AIF immunoreactivity was localized in the nucleus as well as the cytoplasm of a subset of affected motor neurons and reactive astrocytes in the ALS cases, while it was restricted to the cytoplasm of these cells in the control cases. Immunoblot analysis disclosed immunoreactivity for cleaved AIF in both cytoplasmic and nuclear protein extracts at a 57-kDa mobility. Densitometric analysis revealed significant increases in the cytoplasmic cleaved AIF/cytoplasmic ?-actin ratio and the nuclear cleaved AIF/nuclear histone H1 ratio in the ALS group compared with the control group. There was no significant link between the cytoplasmic and nuclear cleaved AIF levels in the ALS spinal cords and the clinical features such as phenotypes, age at death, and disease duration. Our results provide evidence for persistent cleavage and nuclear translocation of AIF in ALS spinal cord, suggesting implications for the AIF-mediated motor neuron death in this disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1432-0533
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
755-62
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Persistent cleavage and nuclear translocation of apoptosis-inducing factor in motor neurons in the spinal cord of sporadic amyotrophic lateral sclerosis patients.
pubmed:affiliation
Department of Pathology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. shibatan@research.twmu.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't