[Molecular and cellular aspects of the cardioprotective mechanism of phosphocreatine].
The present state of investigations on molecular and cellular mechanisms of cardioprotective effects of phosphocreatine (PCr) is reviewed. The protective effect of PCr is manifested as significant improvement of heart contractile function recovery, lowering of diastolic pressure elevation and myocardial enzymes release during postischemic reperfusion as well as better preservation of high energy phosphates in comparison with control. Data from multidisciplinary studies using physico-chemical, physiological, pharmacological etc. approaches suggest that one of the key mechanisms of PCr action is its interaction with the sarcolemmal membrane. The authors own data obtained with the use of spin-labeled ESR-probe incorporated into the isolated sarcolemmal vesicles provide direct evidence in favor of the ordering effect of PCr sarcolemmal phospholipid packing with essential involvement of Ca2+ ions. PCr transform membrane phospholipids into more structured gel-like state. The results of biomedical studies suggest that the mechanism of this protective action is complex and includes at least four components: 1) inhibition of lysophosphoglyceride accumulation in the ischemic myocardium and preservation of cardiac cell sarcolemma structure via zwitterionic interaction with PCr molecules; ii) extracellular action consisting in inhibition of platelet aggregation via ADP removal in the extracellular creatine kinase reaction and increasing plasticity of red blood cells; iii) PCr penetration into cells maintenance of high local ATP levels is possible; iiii) inhibition of adenine nucleotide degradation at the step of 5'-nucleotidase reaction in cardiac cell sarcolemma.
Saks
V A
VA
Schiapparelli-Searle, Medical Research Department, Torino, Italy.
Dzhaliashvili
I V
IV
Konorev
E A
EA
Strumia
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002317:Cardiovascular Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010084:Oxidation-Reduction; D010725:Phosphocreatine / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D010743:Phospholipids / Q000378:metabolism; D012508:Sarcolemma / Q000187:drug effects
D002317:Cardiovascular Agents; D010743:Phospholipids; D010725:Phosphocreatine; D002118:Calcium
Molekuliarnye i kletochnye aspekty mekhanizma kardioprotektivnogo deĭstviia fosfokreatina.