Linked Life Data

9714796

Source:http://linkedlifedata.com/resource/pubmed/id/9714796

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1998-9-21
pubmed:abstractText
Using confocal microscopy, onset of the mitochondrial permeability transition (MPT) in individual mitochondria within living cells can be visualized by the redistribution of the cytosolic fluorophore, calcein, into mitochondria. Simultaneously, mitochondria release membrane potential-indicating fluorophores like tetramethylrhodamine methylester. The MPT occurs in several forms of necrotic cell death, including oxidative stress, pH-dependent ischemia/reperfusion injury and Ca2+ ionophore toxicity. Cyclosporin A (CsA) and trifluoperazine block the MPT in these models and prevent cell killing, showing that the MPT is a causative factor in necrotic cell death. During oxidative injury induced by t-butylhydroperoxide, onset of the MPT is preceded by pyridine nucleotide oxidation, mitochondrial generation of reactive oxygen species, and an increase of mitochondrial free Ca2+, all changes that promote the MPT. During tissue ischemia, acidosis develops. Because of acidotic pH, anoxic cell death is substantially delayed. However, when pH is restored to normal after reperfusion (reoxygenation at pH 7.4), cell death occurs rapidly (pH paradox). This killing is caused by pH-dependent onset of the MPT, which is blocked by reperfusion at acidotic pH or with CsA. In isolated mitochondria, toxicants causing Reye's syndrome, such as salicylate and valproate, induce the MPT. Similarly, salicylate induces a CsA-sensitive MPT and killing of cultured hepatocytes. These in vitro findings suggest that the MPT is the pathophysiological mechanism underlying Reye's syndrome in vivo. Kroemer and coworkers proposed that the MPT is a critical event in the progression of apoptotic cell death. Using confocal microscopy, the MPT can be directly documented during tumor necrosis factor-alpha induced apoptosis in hepatocytes. CsA blocks this MPT and prevents apoptosis. The MPT does not occur uniformly during apoptosis. Initially, a small proportion of mitochondria undergo the MPT, which increases to nearly 100% over 1-3 h. A technique based on fluorescence resonance energy transfer can selectively reveal mitochondrial depolarization. After nutrient deprivation, a small fraction of mitochondria spontaneously depolarize and enter an acidic lysosomal compartment, suggesting that the MPT precedes the normal process of mitochondrial autophagy. A model is proposed in which onset of the MPT to increasing numbers of mitochondria within a cell leads progressively to autophagy, apoptosis and necrotic cell death.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
1366
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
177-96
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9714796-Animals, pubmed-meshheading:9714796-Apoptosis, pubmed-meshheading:9714796-Autophagy, pubmed-meshheading:9714796-Calcimycin, pubmed-meshheading:9714796-Calcium, pubmed-meshheading:9714796-Cells, Cultured, pubmed-meshheading:9714796-Cyclosporine, pubmed-meshheading:9714796-Fluoresceins, pubmed-meshheading:9714796-Hydrogen-Ion Concentration, pubmed-meshheading:9714796-Microscopy, Confocal, pubmed-meshheading:9714796-Mitochondria, pubmed-meshheading:9714796-Mitochondria, Liver, pubmed-meshheading:9714796-Necrosis, pubmed-meshheading:9714796-Oxidative Stress, pubmed-meshheading:9714796-Permeability, pubmed-meshheading:9714796-Peroxides, pubmed-meshheading:9714796-Reactive Oxygen Species, pubmed-meshheading:9714796-Rhodamines, pubmed-meshheading:9714796-Superoxides, pubmed-meshheading:9714796-tert-Butylhydroperoxide
pubmed:year
1998
pubmed:articleTitle
The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy.
pubmed:affiliation
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill, CB No. 7090, 236 Taylor Hall, Chapel Hill, NC 27799-7090, USA. LEMASTER@MED.UNC.EDU
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Review