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Recently we found that the level of anti-infarct tolerance afforded by ischemic preconditioning (IPC) and erythropoietin (EPO) infusion was closely correlated with the level of Ser9-phospho-GSK-3beta upon reperfusion in the heart. To get an insight into the mechanism by which phospho-GSK-3beta protects the myocardium from ischemia/reperfusion injury, we(More)
The aim of the present study was to examine the hypothesis that acceleration of gap junction (GJ) closure during ischemia contributes to anti-infarct tolerance afforded by preconditioning (PC). First, the effects of PC on GJ communication during ischemia were assessed. Isolated buffer-perfused rabbit hearts were subjected to 5-min global ischemia with or(More)
This review takes a critical look at the current effectiveness of reperfusion therapy for acute myocardial infarction and at the potential for cardioprotective agents to improve it. Reperfusion alone limits the median value of infarct size to approximately 50% of the ischemic region. However, the range of infarct sizes is very wide, and one-fourth of these(More)
Glycogen synthase kinase-3β (GSK-3β) is a major positive regulator of the mitochondrial permeability transition pore (mPTP), a principle trigger of cell death, under the condition of oxidative stress. However, the mechanism by which cytosolic GSK-3β translocates to mitochondria, promoting mPTP opening, remains unclear. Here we addressed this issue by(More)
RATIONALE The diabetic heart is resistant to ischemic preconditioning because of diabetes-associated impairment of phosphatidylinositol 3-kinase (PI3K)-Akt signaling. The mechanism by which PI3K-Akt signaling is impaired by diabetes remains unclear. OBJECTIVE Here, we examined the hypothesis that phosphorylation of Jak2 upstream of PI3K is impaired in(More)
OBJECTIVE The aim of this study was to determine the role of AMP-activated protein kinase (AMPK) and its link to protein kinase C (PKC) in the late phase of cardioprotection afforded by ischemic preconditioning (PC) against myocardial stunning. METHODS AND RESULTS Rabbits were instrumented with a balloon occluder around a coronary artery and with a(More)
In spite of the current optimal therapy, the mortality of patients with ischemic heart disease (IHD) remains high, particularly in cases with diabetes mellitus (DM) as a co-morbidity. Myocardial infarct size is a major determinant of prognosis in IHD patients, and development of a novel strategy to limit infarction is of great clinical importance. Ischemic(More)
OBJECTIVE Alteration in endoplasmic reticulum (ER) stress in diabetic hearts and its effect on cytoprotective signaling are unclear. Here, we examine the hypothesis that ER stress in diabetic hearts impairs phospho-glycogen synthase kinase (GSK)-3beta-mediated suppression of mitochondrial permeability transition pore (mPTP) opening, compromising myocardial(More)
Glycogen synthase kinase-3beta (GSK-3beta) is a multifunctional Ser/Thr kinase that plays important roles in necrosis and apoptosis of cardiomyocytes. A major mechanism of cell necrosis is the opening of the mitochondrial permeability transition pore (mPTP), which consists of multiple protein subunits, including adenine nucleotide translocase (ANT). The(More)
We examined whether the mitochondrial ATP-sensitive K channel (K(ATP)) is an effector downstream of protein kinase C-epsilon (PKC-epsilon) in the mechanism of preconditioning (PC) in isolated rabbit hearts. PC with two cycles of 5-min ischemia/5-min reperfusion before 30-min global ischemia reduced infarction from 50.3 +/- 6.8% of the left ventricle to 20.3(More)