Genistein attenuates postischemic depressed myocardial function by increasing myofilament Ca2+ sensitivity in rat myocardium.
The present study investigated whether genistein, a broad-spectrum tyrosine kinase inhibitor, could increase the myofilament Ca(2+) sensitivity and partially reverse postischemic depressed myocardial function. Left ventricular papillary muscles were isolated from adult Wistar rats and loaded with the Ca2+ indicator, aequorin. The use of fluorocarbon immersion with hypoxia simulated a model of ischemia. Myofilament responsiveness to Ca2+ was evaluated from force-[Ca2+]i relationship recorded during tetani in papillary muscles. Protein levels of troponin I (TnI) were measured in postischemic papillary muscles with the Western blot technique. Isometric contraction was depressed during the period of ischemia and remained low after 60 min of reoxygenation without a corresponding significant change of peak [Ca2+]i in the control group (n = 7). In contrast, the depression of isometric contraction was ameliorated during ischemia in muscle preparations in the presence of genistein (2 micro M; n = 8), and postischemic depressed myocardial contractility partially recovered after a 60-min reperfusion. The myofilament Ca2+ responsiveness was significantly increased in papillary muscles in the presence of genistein. Protein levels of TnI were reduced in postischemic papillary muscles, whereas genistein partially restored decreased protein levels of TnI. Our results reveal that genistein produces an effective attenuation of postischemic depressed myocardial function and improves myofibrillar Ca2+ responsiveness in rat myocardium.
The Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Jiang-Yong
JY
Min
Haisun
H
Liao
Ju-Feng
JF
Wang
Matthew F
MF
Sullivan
Toshiro
T
Ito
James P
JP
Morgan
D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000502:physiology; D000331:Aequorin / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D015687:Cell Hypoxia; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005465:Fluorocarbon Polymers / Q000494:pharmacology; D005466:Fluorocarbons; D019833:Genistein / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009124:Muscle Proteins / Q000037:antagonists & inhibitors*; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications*; D017682:Myocardial Stunning / Q000209:etiology / Q000503:physiopathology*; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D019210:Troponin I / Q000378:metabolism
D004791:Enzyme Inhibitors; D005465:Fluorocarbon Polymers; D005466:Fluorocarbons; D009124:Muscle Proteins; D019210:Troponin I; C429307:fluorocarbon 77; D000331:Aequorin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium