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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-2-7
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pubmed:abstractText |
Stimulation of beta-adrenergic receptors (betaARs) causes apoptosis in adult rat ventricular myocytes (ARVMs). The role of reactive oxygen species (ROS) in mediating betaAR-stimulated apoptosis is not known. Stimulation of betaARs with norepinephrine (10 micromol/L) in the presence of prazosin (100 nmol/L) for 24 hours increased the number of apoptotic myocytes as determined by TUNEL staining by 3.6- fold. The superoxide dismutase/catalase mimetics Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP; 10 micromol/L) and Euk-134 decreased betaAR-stimulated apoptosis by 89+/-6% and 76+/-10%, respectively. Infection with an adenovirus expressing catalase decreased betaAR-stimulated apoptosis by 82+/-15%. The mitochondrial permeability transition pore inhibitor bongkrekic acid (50 micromol/L) decreased betaAR-stimulated apoptosis by 76+/-8%, and the caspase inhibitor zVAD-fmk (25 micromol/L) decreased betaAR-stimulated apoptosis by 62+/-11%. betaAR-stimulated cytochrome c release was inhibited by MnTMPyP. betaAR stimulation caused c-Jun NH2-terminal kinase (JNK) activation, which was abolished by MnTMPyP. Transfection with an adenovirus expressing dominant-negative JNK inhibited betaAR-stimulated apoptosis by 81+/-12%, and the JNK inhibitor SP600125 inhibited both betaAR-stimulated apoptosis and cytochrome c release. Thus, betaAR-stimulated apoptosis in ARVMs involves ROS/JNK-dependent activation of the mitochondrial death pathway.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bongkrekic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Catalase,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/EUK-134,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers,
http://linkedlifedata.com/resource/pubmed/chemical/Ion Channels,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloporphyrins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitochondrial Membrane Transport...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Organometallic Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Prazosin,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/Salicylates,
http://linkedlifedata.com/resource/pubmed/chemical/mitochondrial permeability...,
http://linkedlifedata.com/resource/pubmed/chemical/tetrakis(N-methyl-4-pyridiniumyl)por...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1524-4571
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
7
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pubmed:volume |
92
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
136-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12574140-Animals,
pubmed-meshheading:12574140-Apoptosis,
pubmed-meshheading:12574140-Bongkrekic Acid,
pubmed-meshheading:12574140-Caspases,
pubmed-meshheading:12574140-Catalase,
pubmed-meshheading:12574140-Cells, Cultured,
pubmed-meshheading:12574140-Cytochrome c Group,
pubmed-meshheading:12574140-Enzyme Inhibitors,
pubmed-meshheading:12574140-Free Radical Scavengers,
pubmed-meshheading:12574140-Ion Channels,
pubmed-meshheading:12574140-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:12574140-Metalloporphyrins,
pubmed-meshheading:12574140-Mitochondria,
pubmed-meshheading:12574140-Mitochondrial Membrane Transport Proteins,
pubmed-meshheading:12574140-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12574140-Myocytes, Cardiac,
pubmed-meshheading:12574140-Norepinephrine,
pubmed-meshheading:12574140-Organometallic Compounds,
pubmed-meshheading:12574140-Prazosin,
pubmed-meshheading:12574140-Rats,
pubmed-meshheading:12574140-Reactive Oxygen Species,
pubmed-meshheading:12574140-Receptors, Adrenergic, beta,
pubmed-meshheading:12574140-Salicylates,
pubmed-meshheading:12574140-Signal Transduction
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pubmed:year |
2003
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pubmed:articleTitle |
Beta-adrenergic receptor-stimulated apoptosis in cardiac myocytes is mediated by reactive oxygen species/c-Jun NH2-terminal kinase-dependent activation of the mitochondrial pathway.
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pubmed:affiliation |
Myocardial Biology Unit and Cardiovascular Medicine Section, Boston University Medical Center, Boston, Mass 02118, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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