Source:http://linkedlifedata.com/resource/pubmed/id/15528225
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2005-2-11
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pubmed:abstractText |
Mitochondrial permeability transition (MPT) pores have recently been implicated as a potential mediator of myocardial ischemic injury. Nitric oxide (NO) donors induce a powerful late phase of cardioprotection against ischemia-reperfusion injury; however, the cellular mechanisms involved are poorly understood. The role of MPT pores as a target of cardioprotective signaling pathways activated by NO has never been explored in detail. Thus mice were administered the NO donor diethylenetriamine (DETA)/NO (4 doses of 0.1 mg/kg i.v. each) 24 h before 30 min of coronary artery occlusion followed by 24 h of reperfusion. Infarct size was significantly reduced in DETA/NO-treated mice (30 +/- 2% of risk region in treated mice vs. 50 +/- 2% in control mice; P < 0.05), which demonstrates powerful cardioprotection. To examine the role of MPT pores, mice were administered atractyloside (Atr; 25 mg/kg i.v.), which induces adenine nucleotide translocase-dependent MPT, 20 min before ischemia. Atr blocked the infarct-sparing effects of DETA/NO (infarct size, 58 +/- 1 vs. 30 +/- 2% of risk region in DETA/NO; P < 0.05), whereas Atr alone had no effect. Mitochondria isolated from DETA/NO-treated mice exhibited increased resistance to Ca(2+)-induced swelling by 20 micromol/l CaCl(2) or by the higher concentration of 200 micromol/l, which suggests that cardioprotection involves decreased propensity for MPT. Preincubation of mitochondria from control hearts with 30 nmol/l of the pore inhibitor cyclosporin A prevented swelling by 200 micromol/l CaCl(2), thereby confirming that Ca(2+) induces mitochondrial swelling via MPT. In accordance with the effects on infarct size, administration of Atr to the mice significantly abrogated DETA/NO-induced protection against Ca(2+)-induced mitochondrial swelling. These phenotypic alterations were associated with an increase in the antiapoptotic protein Bcl-2, which suggests that the underlying mechanisms may involve inhibition of cell death by Bcl-2. These data suggest that a critical process during NO donor-induced cardioprotection is to prevent MPT pore opening potentially via targeting of the adenine nucleotide translocator.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Atractyloside,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cardiotonic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Donors,
http://linkedlifedata.com/resource/pubmed/chemical/Polyamines,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/diethylenetriamine
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0363-6135
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
288
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
H1290-5
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15528225-Animals,
pubmed-meshheading:15528225-Atractyloside,
pubmed-meshheading:15528225-Calcium,
pubmed-meshheading:15528225-Cardiotonic Agents,
pubmed-meshheading:15528225-Enzyme Inhibitors,
pubmed-meshheading:15528225-Male,
pubmed-meshheading:15528225-Mice,
pubmed-meshheading:15528225-Mice, Inbred ICR,
pubmed-meshheading:15528225-Mitochondria,
pubmed-meshheading:15528225-Mitochondrial Swelling,
pubmed-meshheading:15528225-Myocardial Infarction,
pubmed-meshheading:15528225-Myocardium,
pubmed-meshheading:15528225-Nitric Oxide,
pubmed-meshheading:15528225-Nitric Oxide Donors,
pubmed-meshheading:15528225-Polyamines,
pubmed-meshheading:15528225-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15528225-Up-Regulation
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pubmed:year |
2005
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pubmed:articleTitle |
Nitric oxide donors protect murine myocardium against infarction via modulation of mitochondrial permeability transition.
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pubmed:affiliation |
Department of Physiology, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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