Source:http://linkedlifedata.com/resource/pubmed/id/10899100
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2000-8-3
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| pubmed:abstractText |
BACKGROUND-Catecholamine-induced apoptosis is mediated by activation of the beta-adrenergic signaling pathway. We tested the hypothesis that beta(1)- and beta(2)-adrenergic receptor (AR) subtypes differentially affect apoptosis in adult rat ventricular myocytes in vitro. METHODS AND RESULTS-Myocytes were first exposed to norepinephrine (NE) alone (10 mcmol/L) or NE+atenolol (AT) (10 mcmol/L) for 12 hours. AT, a beta(1)-selective AR antagonist, abolished the NE-induced increase in nick end-labeling (TUNEL)-positive cells compared with control (NE, 33+/-3% versus control, 3+/-1%, P<0.0001; NE+AT, 4+/-2% versus control, 3+/-1%, P=0. 98). Annexin V staining, DNA laddering, and caspase activity determinations corroborated these results. Subsequent experiments under prazosin treatment established the apoptosis dose-response curves for the increasingly beta(2)-selective AR agonists isoproterenol (ISO) (beta(1) approximately beta(2)) and albuterol (ALB) (beta(2)>beta(1)). ISO and ALB induced significantly less apoptosis than NE (beta(1)>beta(2)) at equimolar concentrations as assessed by TUNEL staining [1 mcmol/L: NE (8+/-2%) approximately ISO (7+/-1%)>ALB (2+/-1%); 10 mcmol/L: NE (35+/-2%)>ISO (23+/-1%)>ALB (3+/-1%); 100 mcmol/L: NE (50+/-2%)>ISO (29+/-2%)>ALB (14+/-1%), P<0.0001 except for NE versus ISO at 1 mcmol/L with P=0.62]. ALB-induced apoptosis at 100 mcmol/L was abolished by AT (10 mcmol/L), indicating a beta(1)AR-mediated effect. Importantly, ICI 118551 (0.1 mcmol/L), a highly selective beta(2)AR antagonist, did not decrease the percentage of NE-, ISO-, and ALB-induced apoptosis. Reverse transcription-polymerase chain reaction studies revealed that AT completely reversed the beta-adrenergic signaling-induced changes in the Bcl-2-to-Bax ratio. CONCLUSIONS-These observations provide evidence that beta AR-mediated apoptotic death signaling is largely dissociated from beta(2)ARs and selectively mediated by beta(1)ARs in adult rat ventricular myocytes.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Albuterol,
http://linkedlifedata.com/resource/pubmed/chemical/Atenolol,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/ICI 118551,
http://linkedlifedata.com/resource/pubmed/chemical/Isoproterenol,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Propanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic, beta,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1524-4539
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
18
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| pubmed:volume |
102
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
344-50
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| pubmed:dateRevised |
2005-11-17
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| pubmed:meshHeading |
pubmed-meshheading:10899100-Adrenergic beta-Antagonists,
pubmed-meshheading:10899100-Albuterol,
pubmed-meshheading:10899100-Animals,
pubmed-meshheading:10899100-Apoptosis,
pubmed-meshheading:10899100-Atenolol,
pubmed-meshheading:10899100-Isoproterenol,
pubmed-meshheading:10899100-Male,
pubmed-meshheading:10899100-Myocardium,
pubmed-meshheading:10899100-Norepinephrine,
pubmed-meshheading:10899100-Propanolamines,
pubmed-meshheading:10899100-Protein Isoforms,
pubmed-meshheading:10899100-Proto-Oncogene Proteins,
pubmed-meshheading:10899100-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:10899100-Rats,
pubmed-meshheading:10899100-Rats, Sprague-Dawley,
pubmed-meshheading:10899100-Receptors, Adrenergic, beta,
pubmed-meshheading:10899100-Ventricular Function,
pubmed-meshheading:10899100-bcl-2-Associated X Protein
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| pubmed:year |
2000
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| pubmed:articleTitle |
Beta-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes.
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| pubmed:affiliation |
Department of Anesthesiology, Health Science Center at Brooklyn, State University of New York, USA.
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| pubmed:publicationType |
Journal Article
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