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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2002-8-23
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pubmed:abstractText |
We previously reported that adrenomedullin produced by cardiac myocytes acts as a local modulator in some cardiac disorders. However, the role of adrenomedullin (AM) in cardiomyocyte apoptosis remains to be clarified. The present study investigated the effect of AM on doxorubicin-induced cardiac myocyte apoptosis. Doxorubicin increased the number of cells with pyknotic nuclei and lactate dehydrogenase release, and AM dose-dependently (10(-10)-10(-8)6 M) inhibited these increases produced by doxorubicin. Treatment with AM also suppressed doxorubicin-induced DNA fragmentation and caspase-3 activation. 8-Bromo-cAMP, a cAMP analog, mimicked these antiapoptotic effects of AM. An AM/calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) and a protein kinase A inhibitor H89 attenuated the antiapoptotic effect of AM. CGRP-(8-37) and H89 had no apoptotic effect alone, but accelerated doxorubicin-induced apoptosis. Under serum-free conditions, AM secretion into the culture medium and expression of AM mRNA were significantly increased after treatment with doxorubicin. Hydrogen peroxide scavenger catalase and antioxidant N-acetyl-L-cysteine inhibited the doxorubicin-mediated increase in AM secretion and its gene expression. These results indicate that AM inhibits doxorubicin-induced cardiac myocyte apoptosis through a cAMP-dependent mechanism and suggest that augmented production of AM by doxorubicin has an endogenous antiapoptotic effect. AM, as an autocrine factor, may play a protective role against cardiomyocyte injury by doxorubicin.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/8-Bromo Cyclic Adenosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenomedullin,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin Gene-Related Peptide,
http://linkedlifedata.com/resource/pubmed/chemical/Cardiotonic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Catalase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers,
http://linkedlifedata.com/resource/pubmed/chemical/Isoquinolines,
http://linkedlifedata.com/resource/pubmed/chemical/L-Lactate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/N-(2-(4-bromocinnamylamino)ethyl)-5-...,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Calcitonin Gene-Related...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/calcitonin gene-related peptide...
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0013-7227
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
143
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3515-21
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12193565-8-Bromo Cyclic Adenosine Monophosphate,
pubmed-meshheading:12193565-Acetylcysteine,
pubmed-meshheading:12193565-Adrenomedullin,
pubmed-meshheading:12193565-Animals,
pubmed-meshheading:12193565-Antineoplastic Agents,
pubmed-meshheading:12193565-Antioxidants,
pubmed-meshheading:12193565-Apoptosis,
pubmed-meshheading:12193565-Calcitonin Gene-Related Peptide,
pubmed-meshheading:12193565-Cardiotonic Agents,
pubmed-meshheading:12193565-Catalase,
pubmed-meshheading:12193565-Cyclic AMP,
pubmed-meshheading:12193565-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:12193565-DNA Fragmentation,
pubmed-meshheading:12193565-Doxorubicin,
pubmed-meshheading:12193565-Enzyme Inhibitors,
pubmed-meshheading:12193565-Free Radical Scavengers,
pubmed-meshheading:12193565-Humans,
pubmed-meshheading:12193565-Isoquinolines,
pubmed-meshheading:12193565-L-Lactate Dehydrogenase,
pubmed-meshheading:12193565-Myocardium,
pubmed-meshheading:12193565-Peptide Fragments,
pubmed-meshheading:12193565-Peptides,
pubmed-meshheading:12193565-Rats,
pubmed-meshheading:12193565-Rats, Wistar,
pubmed-meshheading:12193565-Receptors, Calcitonin Gene-Related Peptide,
pubmed-meshheading:12193565-Recombinant Proteins,
pubmed-meshheading:12193565-Sulfonamides
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pubmed:year |
2002
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pubmed:articleTitle |
Adrenomedullin inhibits doxorubicin-induced cultured rat cardiac myocyte apoptosis via a cAMP-dependent mechanism.
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pubmed:affiliation |
Research Institute, National Cardiovascular Center, Suita, Osaka 565-8565, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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