Analysis of protein fragmentation inhibition by an MMP-inhibitor in an in vivo model of heart failure using automated chromatography
| Autor: | J. Randall Slemmon, Karen Kaup, Sashi Nadanaciva, Rachel Scherrer, Virginia Casadas, Florentina Catana, You Yang Zhao, Marcia I. Heron, Cory L. Painter |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Cardiotonic Agents Molecular Sequence Data Clinical Biochemistry Myocardial Infarction Peptide Matrix Metalloproteinase Inhibitors Matrix metalloproteinase Proteomics Peptide Mapping Biochemistry High-performance liquid chromatography Mass Spectrometry Analytical Chemistry Rats Sprague-Dawley In vivo medicine Animals Protease Inhibitors Amino Acid Sequence Solid phase extraction Fragmentation (cell biology) Chromatography High Pressure Liquid chemistry.chemical_classification Chromatography Cell Biology General Medicine medicine.disease Matrix Metalloproteinases Rats chemistry Heart failure Models Animal |
| Zdroj: | Journal of Chromatography B. 819:219-228 |
| ISSN: | 1570-0232 |
| Popis: | Proteomic strategies have continued to demonstrate value in studying disease by exploiting new technologies that can develop significant numbers of measurements from single samples. However, using complex samples such as tissues or blood has continued to be problematic due to the presence of major interfering substances. In this study, a process is described that uses denaturing peptide extraction from whole tissue and automated chromatography in order to allow subsequent analysis of more than 1000 tissue-derived peptides per sample. The process was employed to identify cardiac proteins that were spared degradation by administration of a heart-protecting matrix metalloproteinase (MMP) inhibitor (compound SC-621) following experimental myocardial infarction (MI). HPLC peptide fingerprints were developed from rat heart left ventricles and the resultant integrated peak data was compared across experimental animals. Surprisingly, although protein fragmentation was generally increased in MI hearts, the effect of the MMP inhibitor was only observed on a few species. The results from this study demonstrated that whole-tissue sample enrichment and peptide analysis using HPLC could be linked in order to study the effects of new compounds on a disease state. The system is flexible and amenable to improvements such as incorporating detection by mass spectrometry. |
| Databáze: | OpenAIRE |
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