pubmed-article:12668584 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:12668584 | lifeskim:mentions | umls-concept:C0034721 | lld:lifeskim |
pubmed-article:12668584 | lifeskim:mentions | umls-concept:C0034693 | lld:lifeskim |
pubmed-article:12668584 | lifeskim:mentions | umls-concept:C0079281 | lld:lifeskim |
pubmed-article:12668584 | lifeskim:mentions | umls-concept:C0225828 | lld:lifeskim |
pubmed-article:12668584 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
pubmed-article:12668584 | lifeskim:mentions | umls-concept:C1533691 | lld:lifeskim |
pubmed-article:12668584 | pubmed:issue | 5 | lld:pubmed |
pubmed-article:12668584 | pubmed:dateCreated | 2003-5-5 | lld:pubmed |
pubmed-article:12668584 | pubmed:abstractText | Apoptosis of cardiac myocytes is thought to be a feature of many pathological disorders, including congestive heart failure (CHF) and ischemic heart disease (IHD). Because recent investigations indicate that endothelin-1 (ET-1) plays an important role in CHF and IHD, we investigated the effect of ET-1 on cardiomyocyte apoptosis. The presence of apoptosis in rat cardiomyocytes (H9c2 and neonatal) was evaluated by morphological criteria, electrophoresis of DNA fragments, 4',6'-diamidine-2'-phenylindole staining, and TUNEL analysis. ET-1, but not angiotensin II, prevented apoptosis induced by serum deprivation via ETA receptors in a dose-dependent manner (1 to 100 nmol/L). ET-1 also prevented cytochrome c release from mitochondria to the cytosol. The use of specific pharmacological inhibitors demonstrated that the antiapoptotic effect of ET-1 was mediated through a tyrosine kinase pathway (genistein and AG490) but not through protein kinase C (PKC; calphostin C), mitogen-activated protein kinases (PD98059 and SB203580), or PKA (KT5270) pathways. Adenovirus-mediated gene transfer of kinase-inactive (KI) c-Src reversed the antiapoptotic effect of ET-1. We further investigated whether Bcl-xL, an antiapoptotic molecule, would be upregulated by using a luciferase-based reporter system. ET-1 upregulated Bcl-xL, and this upregulation was inhibited by genistein or AG490 but not by calphostin C. The experiments with KI mutants for various tyrosine kinases revealed that c-Src and Pyk2 (but not JAK1, Jak2, Syk, and Tec) are involved in ET-1-induced upregulation of Bcl-xL expression. These findings suggest that ET-1 prevents apoptosis in cardiac myocytes through the ETA receptor and the subsequent c-Src/Bcl-xL-dependent pathway. | lld:pubmed |
pubmed-article:12668584 | pubmed:language | eng | lld:pubmed |
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pubmed-article:12668584 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:12668584 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:12668584 | pubmed:month | May | lld:pubmed |
pubmed-article:12668584 | pubmed:issn | 1524-4563 | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:OzawaKeiyaK | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:BerkBradford... | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:TakahashiMasa... | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:OgataYukiyoY | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:TakeuchiKoich... | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:KobayashiEiji... | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:IkedaUichiU | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:ShimadaKazuyu... | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:OokawaraShige... | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:OkadaTakashiT | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:ManoHiroyukiH | lld:pubmed |
pubmed-article:12668584 | pubmed:author | pubmed-author:UenoShuichiS | lld:pubmed |
pubmed-article:12668584 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:12668584 | pubmed:volume | 41 | lld:pubmed |
pubmed-article:12668584 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:12668584 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:12668584 | pubmed:pagination | 1156-63 | lld:pubmed |
pubmed-article:12668584 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
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pubmed-article:12668584 | pubmed:year | 2003 | lld:pubmed |
pubmed-article:12668584 | pubmed:articleTitle | Antiapoptotic effect of endothelin-1 in rat cardiomyocytes in vitro. | lld:pubmed |
pubmed-article:12668584 | pubmed:affiliation | Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical School, Tochigi, Japan. | lld:pubmed |
pubmed-article:12668584 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:12668584 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
entrez-gene:50646 | entrezgene:pubmed | pubmed-article:12668584 | lld:entrezgene |
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