| Cardioprotective effects of a novel calpain inhibitor SNJ-1945 for reperfusion injury after cardioplegic cardiac arrest. | |
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MedLine Citation:
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PMID: 19966051 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously indicated that calpain inhibitor-1 prevents the heart from ischemia- reperfusion injury associated with the impairment of total Ca(2+) handling by inhibiting the proteolysis of alpha-fodrin. However, this inhibitor is insoluble with water and inappropriate for clinical application. The aim of the present study was to investigate the protective effect of a newly developed calpain inhibitor, SNJ-1945 (SNJ), with good aqueous solubility on left ventricular (LV) mechanical work and energetics in the cross-circulated rat hearts. SNJ (150 microM) was added to KCl (30 meq) cardioplegia (CP). Mean end-systolic pressure at midrange LV volume (ESP(mLVV)) and systolic pressure-volume area (PVA) at mLVV (PVA(mLVV); a total mechanical energy per beat) were hardly changed after CP plus SNJ arrest-reperfusion (post-CP + SNJ), whereas ESP(mLVV) and PVA(mLVV) in post-CP group were significantly (P < 0.01) decreased. Mean myocardial oxygen consumption for the total Ca(2+) handling in excitation-contraction coupling did not significantly decrease in post-CP + SNJ group, whereas it was significantly (P < 0.01) decreased in post-CP group. The mean amounts of 145- and 150-kDa fragments of alpha-fodrin in the post-CP group were significantly larger than those in normal and post-CP + SNJ groups. In contrast, the mean amounts of L-type Ca(2+) channel and sarcoplasmic reticulum Ca(2+)-ATPase were not significantly different among normal, post-CP, and post-CP + SNJ groups. Our results indicate that soluble SNJ attenuates cardiac dysfunction due to CP arrest-reperfusion injury associated with the impairment of the total Ca(2+) handling in excitation-contraction coupling by inhibiting the proteolysis of alpha-fodrin. |
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Authors:
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Yoshiro Yoshikawa; Guo-Xing Zhang; Koji Obata; Yoshimi Ohga; Hiroko Matsuyoshi; Shigeki Taniguchi; Miyako Takaki |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-04 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 298 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-01-21 Completed Date: 2010-02-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H643-51 Citation Subset: IM |
Affiliation:
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Department of Physiology II, Nara Medical University School of Medicine, Kashihara, Nara, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism Calcium Channels, L-Type / metabolism Calpain / antagonists & inhibitors* Carbamates / therapeutic use* Cardiotonic Agents / therapeutic use* Carrier Proteins / metabolism Disease Models, Animal Heart Arrest, Induced / adverse effects* Male Microfilament Proteins / metabolism Myocardial Reperfusion Injury / etiology*, metabolism, prevention & control* Oxygen Consumption / physiology Rats Rats, Wistar Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism Ventricular Dysfunction, Left / metabolism, physiopathology |
| Grant Support | |
ID/Acronym/Agency:
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//Biotechnology and Biological Sciences Research Council |
| Chemical | |
Reg. No./Substance:
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0/((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester; 0/Calcium Channels, L-Type; 0/Carbamates; 0/Cardiotonic Agents; 0/Carrier Proteins; 0/Microfilament Proteins; 0/fodrin; 7440-70-2/Calcium; EC 3.4.22.-/Calpain; EC 3.6.3.8/Sarcoplasmic Reticulum Calcium-Transporting ATPases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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