Document Detail


Anti-ischemic effect of a novel cardioprotective agent, JTV519, is mediated through specific activation of delta-isoform of protein kinase C in rat ventricular myocardium.
MedLine Citation:
PMID:  10683355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: A new 1,4-benzothiazepine derivative, JTV519, has a strong protective effect against Ca(2+) overload-induced myocardial injury. We investigated the effect of JTV519 on ischemia/reperfusion injury in isolated rat hearts. METHODS AND RESULTS: At 30 minutes of reperfusion after 30-minute global ischemia, the percent recovery of left ventricular developed pressure was improved, and the creatine phosphokinase and lactate dehydrogenase leakage was reduced in a concentration-dependent manner when JTV519 was administered in the coronary perfusate both at 5 minutes before the induction of ischemia and at the time of reperfusion. The myocardial protective effect of JTV519 was completely blocked by pretreatment of the heart with GF109203X, a specific protein kinase C (PKC) inhibitor. In contrast, the effect of JTV519 was not affected by alpha(1)-, A(1)-, and B(2)-receptor blockers that couple with PKC in the cardiomyocyte. Both immunofluorescence images and immunoblots of JTV519-treated left ventricular myocardium and isolated ventricular myocytes demonstrated that this agent induced concentration-dependent translocation of the delta-isoform but not the other isoforms of PKC to the plasma membrane. CONCLUSIONS: The mechanism of cardioprotection by JTV519 against ischemia/reperfusion injury involves isozyme-specific PKC activation through a receptor-independent mechanism. This agent may provide a novel pharmacological approach for the treatment of patients with acute coronary diseases via a subcellular mechanism mimicking ischemic preconditioning.
Authors:
K Inagaki; Y Kihara; W Hayashida; T Izumi; Y Iwanaga; T Yoneda; Y Takeuchi; K Suyama; E Muso; S Sasayama
Related Documents :
20925105 - Force relaxation and thin filament protein phosphorylation during acute myocardial isch...
15147905 - Activation of big map kinase 1 (bmk1/erk5) inhibits cardiac injury after myocardial isc...
11036205 - Induction of vascular endothelial growth factor receptors and phosphatidylinositol 3'-k...
17064355 - Inhibition of mlk3-mkk4/7-jnk1/2 pathway by akt1 in exogenous estrogen-induced neuropro...
1830425 - Evidence that glucocorticosteroid-mediated immunosuppressive effects do not involve alt...
18544565 - Involvement of rad51 in cytotoxicity induced by epidermal growth factor receptor inhibi...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  101     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-08     Completed Date:  2000-03-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  797-804     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport / drug effects
Calcium Channel Blockers / pharmacology*
Enzyme Activation
Isoenzymes / metabolism*
Myocardial Ischemia / prevention & control*
Myocardial Reperfusion Injury / prevention & control
Myocardium / enzymology*
Protein Kinase C / metabolism*
Protein Kinase C-delta
Rats
Thiazepines / pharmacology*
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Isoenzymes; 0/K201 compound; 0/Thiazepines; EC 2.7.1.-/Prkcd protein, rat; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.13/Protein Kinase C-delta

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcop...
Next Document:  Red wine polyphenols inhibit proliferation of vascular smooth muscle cells and downregulate expressi...