Linked Life Data

11520895

Source:http://linkedlifedata.com/resource/pubmed/id/11520895

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-8-24
pubmed:abstractText
Using the inactivation of mitochondrial and cytosolic aconitases as markers of compartment-specific superoxide (O2(-)) production, we show that oxygen-glucose deprivation (OGD) or excitotoxin exposure produce a time-dependent inactivation of mitochondrial, but not cytosolic, aconitase in cortical cultures. To determine if mitochondrial O2(-) production was an important determinant in neuronal death resulting from OGD, metalloporphyrins with varying superoxide dismutase (SOD) activity were tested for their ability to protect against mitochondrial aconitase inactivation and cell death. OGD-induced mitochondrial aconitase inactivation and cell death was inhibited by manganese tetrakis (4-benzoic acid) porphyrin (MnTBAP), manganese tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) and NMDA receptor antagonists. By contrast, NMDA- or kainate (KA)-induced mitochondrial aconitase inactivation and cell death was inhibited by MnTBAP, but not MnTE-2-PyP. Moreover, both MnTBAP and MnTE-2-PyP penetrated mitochondrial fractions of cortical cells. These data suggest that mitochondrial aconitase inactivation closely correlates with subsequent neuronal death following excitotoxicity produced by OGD or NMDA/KA exposure. Assessment of biological rather biochemical antioxidant activities better predicted neuroprotection by metalloporphyrins. Moreover, antioxidants that protect oxidant-sensitive mitochondrial targets such as aconitase may be useful as therapies for disease states involving excitotoxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
746-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11520895-Aconitate Hydratase, pubmed-meshheading:11520895-Animals, pubmed-meshheading:11520895-Astrocytes, pubmed-meshheading:11520895-Cell Death, pubmed-meshheading:11520895-Cell Fractionation, pubmed-meshheading:11520895-Cells, Cultured, pubmed-meshheading:11520895-Enzyme Inhibitors, pubmed-meshheading:11520895-Fumarate Hydratase, pubmed-meshheading:11520895-Glucose, pubmed-meshheading:11520895-Kainic Acid, pubmed-meshheading:11520895-Metalloporphyrins, pubmed-meshheading:11520895-Mitochondria, pubmed-meshheading:11520895-N-Methylaspartate, pubmed-meshheading:11520895-Nerve Degeneration, pubmed-meshheading:11520895-Neurons, pubmed-meshheading:11520895-Neuroprotective Agents, pubmed-meshheading:11520895-Neurotoxins, pubmed-meshheading:11520895-Oxygen, pubmed-meshheading:11520895-Paraquat, pubmed-meshheading:11520895-Rats, pubmed-meshheading:11520895-Superoxides
pubmed:year
2001
pubmed:articleTitle
Dependence of excitotoxic neurodegeneration on mitochondrial aconitase inactivation.
pubmed:affiliation
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't