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In vivo matrix metalloproteinase-7 substrates identified in the left ventricle post-myocardial infarction using proteomics.
MedLine Citation:
PMID:  20232908     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Matrix metalloproteinase-7 (MMP-7) deletion has been shown to improve survival after myocardial infarction (MI). MMP-7 has a large array of in vitro substrates, but in vivo substrates for MMP-7 following MI have not been fully identified. Accordingly, we evaluated the infarct regions of wild-type (WT; n = 12) and MMP-7 null (null; n = 10) mice using a proteomic strategy. Seven days post-MI, infarct regions of the left ventricles were excised, homogenized, and protein extracts were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Of 13 spots that showed intensity differences between WT and null, the intensities of eight spots were higher and those of five spots were lower in the null group (p < 0.05). Fibronectin and tenascin-C, known in vitro substrates of MMP-7, were identified in spots that showed lower intensity in the null. Immunoblotting and in vitro cleavage assays confirmed reduced fibronectin and tenascin-C fragment generation in the null, and this effect was restored by exogenous administration of MMP-7. Lower levels of full-length peroxiredoxin-1 and -2 and higher levels of the full-length peroxiredoxin-3 were detected in the null group, suggesting MMP-7 deletion may also indirectly regulate protein levels through nonenzymatic mechanisms. In conclusion, this is the first study to identify fibronectin and tenascin-C as in vivo MMP-7 substrates in the infarcted left ventricle using a proteomic approach.
Authors:
Ying Ann Chiao; Rogelio Zamilpa; Elizabeth F Lopez; Qiuxia Dai; Gladys P Escobar; Kevin Hakala; Susan T Weintraub; Merry L Lindsey
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of proteome research     Volume:  9     ISSN:  1535-3907     ISO Abbreviation:  J. Proteome Res.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-07     Completed Date:  2010-08-12     Revised Date:  2013-02-18    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2649-57     Citation Subset:  IM    
Affiliation:
Department of Medicine, Division of Cardiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Electrophoresis, Gel, Two-Dimensional
Fibronectins / analysis,  metabolism
Heart Ventricles / anatomy & histology,  enzymology*,  pathology
Immunoblotting
Male
Mass Spectrometry
Matrix Metalloproteinase 7 / genetics,  metabolism*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Myocardial Infarction / enzymology*
Myocardium / enzymology*
Peroxiredoxins / analysis,  metabolism
Proteomics / methods*
Tenascin / analysis,  metabolism
Ventricular Remodeling / physiology*
Grant Support
ID/Acronym/Agency:
HL75360/HL/NHLBI NIH HHS; R01 HL075360/HL/NHLBI NIH HHS; R01 HL075360-06/HL/NHLBI NIH HHS; R01 HL075360-06S1/HL/NHLBI NIH HHS; R01 HL075360-09/HL/NHLBI NIH HHS; T32 HL07446/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Fibronectins; 0/Tenascin; EC 1.11.1.15/Peroxiredoxins; EC 3.4.24.23/Matrix Metalloproteinase 7
Comments/Corrections

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