Document Detail

Erythropoietin protects post-ischemic hearts by preventing extracellular matrix degradation: role of Jak2-ERK pathway.
MedLine Citation:
PMID:  17707437     Owner:  NLM     Status:  MEDLINE    
Factors predisposing to extracellular matrix degradation associated with myocardial ischemia/reperfusion (IR) usually cause cell death. Recombinant human erythropoietin (EPO) protects the myocardium from IR, but whether it affects extracellular matrix (ECM) degradation is not known. This study examined the effect of the Jak2-ERK pathway, which is triggered by EPO, on the expression of matrix metalloproteinases (MMPs), tissue inhibitor of MMP 4 (TIMP-4), and collagen in post-ischemic hearts. Rat hearts were isolated and perfused in a Langendorff apparatus. IR was induced by 40 min of stopped flow and 120 min of aerobic reperfusion; EPO was added immediately before reperfusion. Compared to untreated controls, poor recovery of the left ventricular developed pressure (LVDP) was seen in IR hearts. IR resulted in myocyte injury measured by creatine kinase MB release and infarction. Western blot analysis showed increased levels of MMP-2 and MMP-9 and reduced levels of TIMP-4 and collagen III. IR rats given 5 IU/ml of EPO showed improved LVDP with reduced injury. EPO increased Jak2 and ERK activity, decreased MMP expression, increased TIMP-4 expression, and prevented collagen degradation in IR hearts. All these effects were blocked by the upstream ERK inhibitor, U0126 (5 microM). These observations show that EPO attenuates extracellular matrix degradation following IR and this may be the basis of the protection from cell death. Jak2-ERK phosphorylation may be an important signal in this process.
Chih-Yang Chan; Yih-Sharng Chen; Hsang-Hsing Lee; Ho-Shiang Huang; Yih-Loong Lai; Chau-Fong Chen; Ming-Chieh Ma
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-07-26
Journal Detail:
Title:  Life sciences     Volume:  81     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-27     Completed Date:  2007-10-12     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  717-23     Citation Subset:  IM    
Department of Surgery, Cardiovascular Division, Far Eastern Memorial Hospital, 21, Sec. 2, Nanya S. Road, Panchaio 220, Taiwan.
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MeSH Terms
Cardiotonic Agents / pharmacology*
Collagen / biosynthesis
Enzyme Inhibitors / pharmacology
Erythropoietin / pharmacology*
Extracellular Matrix / drug effects*,  enzymology,  metabolism
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors,  biosynthesis,  physiology*
Heart / drug effects*
Janus Kinase 2 / biosynthesis,  physiology*
Matrix Metalloproteinases / biosynthesis
Myocardial Reperfusion Injury* / enzymology,  metabolism
Myocardium / enzymology,  metabolism
Rats, Wistar
Recombinant Proteins
Tissue Inhibitor of Metalloproteinases / biosynthesis
Ventricular Function, Left / drug effects
Reg. No./Substance:
0/Cardiotonic Agents; 0/Enzyme Inhibitors; 0/Recombinant Proteins; 0/Tissue Inhibitor of Metalloproteinases; 0/epoetin beta; 0/tissue inhibitor of metalloproteinase-4; 11096-26-7/Erythropoietin; 9007-34-5/Collagen; EC Kinase 2; EC protein, rat; EC Signal-Regulated MAP Kinases; EC 3.4.24.-/Matrix Metalloproteinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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