In vivo Matrix Metalloproteinase-7 Substrates Identified in the Left Ventricle Post-Myocardial Infarction Using Proteomics
| Autor: | Susan T. Weintraub, Elizabeth F. Lopez, Qiuxia Dai, Ying Ann Chiao, Gladys Patricia Escobar, Kevin Hakala, Merry L. Lindsey, Rogelio Zamilpa |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Proteomics Heart Ventricles Immunoblotting Myocardial Infarction Mice Transgenic Matrix metalloproteinase Matrix (biology) Biochemistry Mass Spectrometry Article Mice In vivo medicine Animals Electrophoresis Gel Two-Dimensional Gel electrophoresis Ventricular Remodeling biology Myocardium Null (mathematics) Tenascin Peroxiredoxins General Chemistry Anatomy Molecular biology In vitro Fibronectins Mice Inbred C57BL Fibronectin medicine.anatomical_structure Ventricle Matrix Metalloproteinase 7 biology.protein |
| Zdroj: | Journal of Proteome Research. 9:2649-2657 |
| ISSN: | 1535-3907 1535-3893 |
| DOI: | 10.1021/pr100147r |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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