Linked Life Data

15269216

Source:http://linkedlifedata.com/resource/pubmed/id/15269216

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2004-9-20
pubmed:abstractText
Human mitochondrial complex I (NADH:ubiquinone oxidoreductase) of the oxidative phosphorylation system is a multiprotein assembly comprising both nuclear and mitochondrially encoded subunits. Deficiency of this complex is associated with numerous clinical syndromes ranging from highly progressive, often early lethal encephalopathies, of which Leigh disease is the most frequent, to neurodegenerative disorders in adult life, including Leber's hereditary optic neuropathy and Parkinson disease. We show here that the cytosolic Ca2+ signal in response to hormonal stimulation with bradykinin was impaired in skin fibroblasts from children between the ages of 0 and 5 years with an isolated complex I deficiency caused by mutations in nuclear encoded structural subunits of the complex. Inhibition of mitochondrial Na+-Ca2+ exchange by the benzothiazepine CGP37157 completely restored the aberrant cytosolic Ca2+ signal. This effect of the inhibitor was paralleled by complete restoration of the bradykinin-induced increases in mitochondrial Ca2+ concentration and ensuing ATP production. Thus, impaired mitochondrial Ca2+ accumulation during agonist stimulation is a major consequence of human complex I deficiency, a finding that may provide the basis for the development of new therapeutic approaches to this disorder.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:copyrightInfo
Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
40328-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15269216-Adenosine Triphosphate, pubmed-meshheading:15269216-Bradykinin, pubmed-meshheading:15269216-Calcium, pubmed-meshheading:15269216-Cell Nucleus, pubmed-meshheading:15269216-Clonazepam, pubmed-meshheading:15269216-Cytosol, pubmed-meshheading:15269216-Electron Transport Complex I, pubmed-meshheading:15269216-Fibroblasts, pubmed-meshheading:15269216-Fluorescent Dyes, pubmed-meshheading:15269216-Humans, pubmed-meshheading:15269216-Ionomycin, pubmed-meshheading:15269216-Leigh Disease, pubmed-meshheading:15269216-Luciferases, pubmed-meshheading:15269216-Membrane Potentials, pubmed-meshheading:15269216-Microscopy, Fluorescence, pubmed-meshheading:15269216-Mitochondria, pubmed-meshheading:15269216-Mitochondrial Encephalomyopathies, pubmed-meshheading:15269216-Oxygen, pubmed-meshheading:15269216-Parkinson Disease, pubmed-meshheading:15269216-Skin, pubmed-meshheading:15269216-Sodium-Calcium Exchanger, pubmed-meshheading:15269216-Thiazepines, pubmed-meshheading:15269216-Time Factors
pubmed:year
2004
pubmed:articleTitle
Inhibition of mitochondrial Na+-Ca2+ exchange restores agonist-induced ATP production and Ca2+ handling in human complex I deficiency.
pubmed:affiliation
Department of Biochemistry and Pediatrics, University Medical Center Nijmegen, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't