Linked Life Data

12169648

Source:http://linkedlifedata.com/resource/pubmed/id/12169648

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-8-9
pubmed:abstractText
In this study, we provide evidence for the operation of BNIP3 as a key regulator of mitochondrial function and cell death of ventricular myocytes during hypoxia. In contrast to normoxic cells, a 5.6-fold increase (P<0.05) in myocyte death was observed in cells subjected to hypoxia. Moreover, a significant increase in BNIP3 expression was detected in postnatal ventricular myocytes and adult rat hearts subjected to hypoxia. An increase in BNIP3 expression was detected in adult rat hearts in vivo with chronic heart failure. Subcellular fractionation experiments indicated that endogenous BNIP3 was integrated into the mitochondrial membranes during hypoxia. Adenovirus-mediated delivery of full-length BNIP3 to myocytes was toxic and provoked an 8.3-fold increase (P<0.05) in myocyte death with features typical of apoptosis. Mitochondrial defects consistent with opening of the permeability transition pore (PT pore) were observed in cells expressing BNIP3 but not in cells expressing BNIP3 missing the carboxyl-terminal transmembrane domain (BNIP3DeltaTM), necessary for mitochondrial insertion. The pan-caspase inhibitor z-VAD-fmk (25 to 100 micromol/L) suppressed BNIP3-induced cell death of ventricular myocytes in a dose-dependent manner. Bongkrekic acid (50 micromol/L), an inhibitor of the PT pore, prevented BNIP3-induced mitochondrial defects and cell death. Expression of BNIP3DeltaTM suppressed the hypoxia-induced integration of the endogenous BNIP3 protein and cell death of ventricular myocytes. To our knowledge, the data provide the first evidence for the involvement of BNIP3 as an inducible factor that provokes mitochondrial defects and cell death of ventricular myocytes during hypoxia.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
91
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
226-31
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12169648-Animals, pubmed-meshheading:12169648-Apoptosis, pubmed-meshheading:12169648-Cell Hypoxia, pubmed-meshheading:12169648-Cells, Cultured, pubmed-meshheading:12169648-Heart Failure, pubmed-meshheading:12169648-Heart Ventricles, pubmed-meshheading:12169648-Intracellular Membranes, pubmed-meshheading:12169648-Ion Channels, pubmed-meshheading:12169648-Membrane Proteins, pubmed-meshheading:12169648-Mitochondria, pubmed-meshheading:12169648-Mitochondrial Membrane Transport Proteins, pubmed-meshheading:12169648-Mutation, pubmed-meshheading:12169648-Permeability, pubmed-meshheading:12169648-Proto-Oncogene Proteins, pubmed-meshheading:12169648-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:12169648-Rats, pubmed-meshheading:12169648-Rats, Sprague-Dawley, pubmed-meshheading:12169648-Tumor Suppressor Proteins
pubmed:year
2002
pubmed:articleTitle
Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes.
pubmed:affiliation
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, and the Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't