Linked Life Data

16319717

Source:http://linkedlifedata.com/resource/pubmed/id/16319717

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2005-12-1
pubmed:abstractText
X-linked adreno-leukodystrophy is a progressive, systemic peroxisomal disorder that affects primarily nervous system myelin and axons as well as the adrenal cortex. Several divergent clinical phenotypes can occur in the same family; thus, there is no correlation between the clinical phenotype and the mutation in the ABCD1 gene in this disease. The most urgent and unresolved clinical issue is the fulminant inflammatory (immune) demyelination of the central nervous system in which a variety of cellular participants, cytokines, and chemokines are noted. A knockout mouse model exhibits mitochondrial deficits and axonal degeneration, but not inflammatory demyelination. To determine whether oxidative stress and damage might play a pathogenic role, we assessed standard biochemical and immunohistochemical markers of such activity both in our knockout mouse model and patients. We find that oxidative stress, as judged by increased immunoreactivity for the mitochondrial manganese-superoxide dismutase, is present in the knockout mouse liver, adrenal cortex, and renal cortex, tissues that normally express high levels of ABCD1 but no evidence of oxidative damage. The brain does not exhibit either oxidative stress or damage. On the other hand, both the human adrenal cortex and brain show evidence of oxidative stress (e.g. hemoxygenase-1 and manganese-superoxide dismutase) and oxidative damage, particularly from lipid peroxidation (4-hydroxynonenal and malondialdehyde). The presence of nitrotyrosylated proteins is strong circumstantial evidence for the participation of the highly toxic peroxynitrite molecule, whereas the demonstration of interferon gamma and interleukin-12 is indicative of a TH1 response in the inflammatory demyelinative lesions of the cerebral phenotype. These differences between the adreno-leukodystrophy mouse and human patients are intriguing and may provide a clue to the phenotypic divergence in this disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-3069
pubmed:author
pubmed:issnType
Print
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1067-79
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16319717-Adrenal Cortex, pubmed-meshheading:16319717-Adrenoleukodystrophy, pubmed-meshheading:16319717-Animals, pubmed-meshheading:16319717-Biochemistry, pubmed-meshheading:16319717-Biological Markers, pubmed-meshheading:16319717-Brain, pubmed-meshheading:16319717-Chemokine CCL22, pubmed-meshheading:16319717-Chemokines, CC, pubmed-meshheading:16319717-Humans, pubmed-meshheading:16319717-Immunohistochemistry, pubmed-meshheading:16319717-Interferon-gamma, pubmed-meshheading:16319717-Interleukin-12, pubmed-meshheading:16319717-Kidney Cortex, pubmed-meshheading:16319717-Liver, pubmed-meshheading:16319717-Mice, pubmed-meshheading:16319717-Mice, Knockout, pubmed-meshheading:16319717-Mitochondria, pubmed-meshheading:16319717-Oxidative Stress, pubmed-meshheading:16319717-Superoxide Dismutase, pubmed-meshheading:16319717-Tyrosine
pubmed:year
2005
pubmed:articleTitle
Adreno-leukodystrophy: oxidative stress of mice and men.
pubmed:affiliation
Department of Pathology, University of Rochester Medical Center, Rochester, New York, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural