Document Detail

Inhibition of Ras-GTPase, but not tyrosine kinases or Ca2+/calmodulin-dependent protein kinase II, improves recovery of cardiac function in the globally ischemic heart.
MedLine Citation:
PMID:  15124905     Owner:  NLM     Status:  MEDLINE    
The signaling pathways involved in ischemic heart disease are not well characterized. In this study, the roles of Ras-GTPase, tyrosine kinases (TKs) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in global ischemia and reperfusion (I/R) in a perfused rat heart model were investigated and compared to beneficial effects produced by preconditioning (PC). A 40 min episode of global ischemia followed by a 30 min reperfusion in perfused rat hearts produced significantly impaired cardiac function, measured as left ventricular developed pressure (Pmax) and left ventricular end-diastolic pressure (LVEDP), and impaired coronary hemodynamics, measured as coronary flow (CF) and coronary vascular resistance (CVR). Hearts from male Wistar rats pre-treated with the tyrosine kinase inhibitor, genistein (1 mg/kg/day for 6 days), or the CaMKII inhibitor, KN-93 (578 ng/min for 6 days), produced detrimental effects on recovery of cardiac function and coronary hemodynamics. In contrast, pre-treatment with Ras-GTPase inhibitor FPT III (232 ng/min for 6 days) significantly enhanced cardiac recovery in terms of left ventricular contractility and coronary vascular hemodynamics. Treatment with FPT III also significantly reduced expression of the sodium-hydrogen exchanger-1 (NHE-1) which was elevated during I/R as detected by Western blotting. These data suggest that TKs and CaMKII are involved in signaling pathways leading to recovery from cardiac ischemia, whereas activation of Ras-GTPase signaling pathways are critical in the development of cardiac dysfunction due to I/R.
Ibrahim F Benter; Jasbir S Juggi; Islam Khan; Saghir Akhtar
Related Documents :
2251985 - Changes in myocardial ischemic threshold during daily activities.
8853335 - Cardioprotection with ischemic preconditioning and mla: role of adenosine-regulating en...
9950835 - An adenosine agonist and preconditioning shift the distribution of myocardial blood flo...
10226865 - Role of angiotensin in cardioprotective effect of ischemic preconditioning.
21417265 - Characterization of the human myocardial proteome in inflammatory dilated cardiomyopath...
16488685 - Conversion to sinus rhythm by ablation improves quality of life in patients submitted t...
Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  259     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-05-04     Completed Date:  2005-01-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  35-42     Citation Subset:  IM    
Department of Pharmacology, Faculty of Medicine, Kuwait University, Safat, Kuwait.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Alkyl and Aryl Transferases / antagonists & inhibitors*,  metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*,  metabolism
Coronary Circulation / drug effects,  physiology
Enzyme Inhibitors / administration & dosage*
Injections, Intraperitoneal
Ischemic Preconditioning, Myocardial
Myocardial Contraction / drug effects,  physiology
Myocardial Ischemia / enzymology*,  physiopathology
Myocardial Reperfusion
Myocardium / enzymology*,  pathology
Protein-Tyrosine Kinases / antagonists & inhibitors*,  metabolism
Rats, Wistar
Recovery of Function / drug effects*,  physiology
Ventricular Pressure / drug effects,  physiology
Reg. No./Substance:
0/Enzyme Inhibitors; EC 2.5.-/Alkyl and Aryl Transferases; EC 2.5.1.-/p21(ras) farnesyl-protein transferase; EC Kinases; EC Protein Kinase Type 2; EC Protein Kinases

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

Previous Document:  Glucuronic acid is a novel inducer of heat shock response.
Next Document:  Caspase-3: its potential involvement in Cr(III)-induced apoptosis of lymphocytes.