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rdf:type |
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lifeskim:mentions |
umls-concept:C0021289,
umls-concept:C0028351,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0162638,
umls-concept:C0205263,
umls-concept:C0225336,
umls-concept:C1150587,
umls-concept:C1367731,
umls-concept:C1704259,
umls-concept:C1705632,
umls-concept:C1705987,
umls-concept:C1879547
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pubmed:issue |
11
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pubmed:dateCreated |
2006-11-6
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pubmed:abstractText |
Our previous study demonstrated that norepinephrine (NE) induces endothelial apoptosis mainly through down-regulation of Bcl-2 protein and activation of the beta-adrenergic and caspase-2 pathways. However, whether reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) are involved in this signal transduction remains unknown. Endothelial cells cultured from neonatal rat heart were treated with 100 microM NE. Proteins of MAPKs and Bcl-2 family were assayed by Western blotting. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated nick end-labeling assay. ROS was analyzed with flow cytometry. Caspase activity was measured using specific fluorogenic substrates. Treatment with NE increased intracellular ROS level and extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 phosphorylation. Whereas the phosphorylated form of Akt was decreased. The NE-induced apoptosis was abrogated by SP600125 (a specific inhibitor of JNK). Antioxidants such as vitamin C and N-acetyl cysteine inhibited NE-induced ROS production, JNK phosphorylation, caspase activation and apoptosis. Exogenously added superoxide dismutase or catalase markedly diminished NE-induced ROS production and cell death. In conclusions, our study is the first report documenting that NE induces apoptosis in neonatal rat endothelial cells via a ROS-dependent JNK activation pathway. Antioxidants may be useful in the prevention and management of NE-mediated endothelial apoptosis during heart failure.
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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/Acetylcysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Ascorbic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Hydrogen Peroxide,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Adrenergic
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1360-8185
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2053-63
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17041759-Acetylcysteine,
pubmed-meshheading:17041759-Animals,
pubmed-meshheading:17041759-Animals, Newborn,
pubmed-meshheading:17041759-Antioxidants,
pubmed-meshheading:17041759-Apoptosis,
pubmed-meshheading:17041759-Ascorbic Acid,
pubmed-meshheading:17041759-Down-Regulation,
pubmed-meshheading:17041759-Endothelial Cells,
pubmed-meshheading:17041759-Enzyme Activation,
pubmed-meshheading:17041759-Hydrogen Peroxide,
pubmed-meshheading:17041759-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:17041759-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:17041759-Myocardium,
pubmed-meshheading:17041759-NADPH Oxidase,
pubmed-meshheading:17041759-Norepinephrine,
pubmed-meshheading:17041759-Phosphorylation,
pubmed-meshheading:17041759-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17041759-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:17041759-Rats,
pubmed-meshheading:17041759-Rats, Sprague-Dawley,
pubmed-meshheading:17041759-Reactive Oxygen Species,
pubmed-meshheading:17041759-Receptors, Adrenergic,
pubmed-meshheading:17041759-Signal Transduction
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pubmed:year |
2006
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pubmed:articleTitle |
Norepinephrine induces apoptosis in neonatal rat endothelial cells via a ROS-dependent JNK activation pathway.
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pubmed:affiliation |
Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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