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Proteome analysis of myocardial tissue following ischemia and reperfusion--effects of complement inhibition.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2006 Oct; Vol. 1764 (10), pp. 1536-45. Date of Electronic Publication: 2006 May 15. - Publication Year :
- 2006
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Abstract
- Myocardial ischemia-reperfusion injury can be related to complement activation with generation of chemotactic mediators, release of cytokines, leukocyte accumulation, and subsequent severe tissue injury. In this regard, activation of transcription factors (i.e., NFkappaB) and de novo protein synthesis or inflammatory protein degradation seems to play an important role. In the present study, we analyzed the cardiac protein expression following myocardial ischemia (60 min) and reperfusion (180 min) in a rabbit model utilizing two-dimensional electrophoresis and nanoHPLC/ESI-MS/MS for biochemical protein identification. To achieve cardioprotective effects, we used a novel highly selective small molecule C1s inhibitor administered 5 min prior to reperfusion. The reduction of myocardial injury was observed as diminished plasma creatine kinase activity in C1s-INH-248-treated animals (65.2+/-3 vs. 38.5+/-3 U/g protein after 3 h of reperfusion, P<0.05). With proteome analysis we were able to detect 509+/-21 protein spots on the gels of the 3 groups. A pattern of 480 spots with identical positions was found on every gel of myocardial tissue of sham animals, vehicle and C1s-INH-248-treated animals. We analyzed 11 spots, which were identified by mass spectrometry: Superoxide dismutase, alpha-crystallin-chain-B, mitochondrial stress protein, Mn SOD, ATP synthase A chain heart isoform, creatine kinase, and troponin T. All of these proteins were significantly decreased in the vehicle group when we compared to sham-treated animals. Treatment with C1s-INH-248 preserved levels of these proteins. Thus, blocking the classical complement pathway with a highly specific and potent synthetic inhibitor of the activated C1 complex archives cardio-protection by altering and preserving different anti-inflammatory and cytoprotective cascades.
- Subjects :
- Amino Acid Sequence
Animals
Biomarkers analysis
Complement C1 Inactivator Proteins pharmacology
Complement System Proteins drug effects
Creatine Kinase analysis
Electrocardiography
Male
Microtubule-Associated Proteins analysis
Molecular Sequence Data
Myocardial Ischemia pathology
Myocardial Ischemia physiopathology
Myocardial Reperfusion Injury pathology
Myocardial Reperfusion Injury physiopathology
Myocardium pathology
Necrosis pathology
Neutrophils physiology
Rabbits
Superoxide Dismutase analysis
Superoxide Dismutase chemistry
alpha-Crystallin B Chain analysis
Complement System Proteins physiology
Myocardial Ischemia metabolism
Myocardial Reperfusion Injury metabolism
Myocardium metabolism
Proteome analysis
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1764
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 17045855
- Full Text :
- https://doi.org/10.1016/j.bbapap.2006.03.008