C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling

Abstract

pusamy. C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling. Am J Physiol Heart Circ Physiol 290: H2136 -H2145, 2006. First published December 22, 2005 doi:10.1152/ajpheart.01072.2005.-We previously showed that C-phycocyanin (PC), an antioxidant biliprotein pigment of Spirulina platensis (a blue-green alga), effectively inhibited doxorubicininduced oxidative stress and apoptosis in cardiomyocytes. Here we investigated the cardioprotective effect of PC against ischemia-reperfusion (I/R)-induced myocardial injury in an isolated perfused Langendorff heart model. Rat hearts were subjected to 30 min of global ischemia at 37°C followed by 45 min of reperfusion. Hearts were perfused with PC (10 M) or Spirulina preparation (SP, 50 mg/l) for 15 min before the onset of ischemia and throughout reperfusion. After 45 min of reperfusion, untreated (control) hearts showed a significant decrease in recovery of coronary flow (44%), left ventricular developed pressure (21%), and rate-pressure product (24%), an increase in release of lactate dehydrogenase and creatine kinase in coronary effluent, significant myocardial infarction (44% of risk area), and TdT-mediated dUTP nick end labelpositive apoptotic cells compared with the preischemic state. PC or SP significantly enhanced recovery of heart function and decreased infarct size, attenuated lactate dehydrogenase and creatine kinase release, and suppressed I/R-induced free radical generation. PC reversed I/R-induced activation of p38 MAPK, Bax, and caspase-3, suppression of Bcl-2, and increase in TdT-mediated dUTP nick end label-positive apoptotic cells. However, I/R also induced activation of ERK1/2, which was enhanced by PC treatment. Overall, these results for the first time showed that PC attenuated I/R-induced cardiac dysfunction through its antioxidant and antiapoptotic actions and modulation of p38 MAPK and ERK1/2. oxidative stress; apoptosis; Spirulina; antioxidant; reactive oxygen species; free radicals THE HEART IS SUBJECTED to episodes of ischemia, followed by reperfusion, in a number of situations, including angina, myocardial infarction, and cardiac surgery. These stresses can result in cell injury and death. The pathogenesis of myocardial ischemia-reperfusion (I/R) injury involves the interplay of multiple mechanisms. Numerous studies have indicated the role of oxidative damage mediated by activation of xanthine oxidase and subsequent formation of reactive oxygen species (ROS), including O 2 Ϫ ⅐, H 2 O 2 , ⅐OH, and peroxynitrite, lipid peroxidation of myocardial membranes, action of iron, decrease in GSH, altered GSH-to-GSSG ratio, depletion of highenergy phosphates including ATP, depressed energy metabolism, and altered calcium homeostasis in the pathogenesis of

The protective effect of picroside II against hypoxia/reoxygenation injury in neonatal rat cardiomyocytes

“…The reperfusion-induced ROS generation is markedly accompanied by reduction of endogenous antioxidants (SOD, GSH-Px, and GSH) (Khan et al, 2006). In this study, we also found that cardiomyocytes subjected to H/R caused a marked reduction of cell viability and elevation of oxidative stress accompanied by MDA production and LDH release, and reduction in SOD and GSH-Px activities.…”

Trimetazidine, Administered at the Onset of Reperfusion, Ameliorates Myocardial Dysfunction and Injury by Activation of p38 Mitogen-Activated Protein Kinase and Akt Signaling

“…MAPKs, namely, p38 MAPK, ERK1/2, and c-Jun NH 2 -terminal kinase are activated in the I/R hearts and modulate oxidant-mediated tissue injury (Armstrong, 2004). Several cardioprotective pharmacological agents are known to mitigate the I/R-mediated oxidative stress through modulation of Akt, p38 MAPK, or ERK1/2 activities (Toth et al, 2003;Liu et al, 2004;Takada et al, 2004;Khan et al, 2006). Our results revealed an increased activation of phospo-p38 MAPK in the hearts treated with TMZ at reperfusion.…”

Cardioprotection by HO-4038, a novel verapamil derivative, targeted against ischemia and reperfusion-mediated acute myocardial infarction

“…4). The infusion of both verapamil and HO-4038 caused a significant increase (28 -30 mmHg) from baseline (18)(19)(20). The increase in myocardial PO 2 may be attributed to a reduction in oxygen demand due to the negative chronotropic effect of these drugs.…”

“…Various studies have demonstrated that Akt has antiapoptotic effects (2,31). Several pharmacological agents have been shown to be cardioprotective by modulating the Akt activity (2,19,55). The antiapoptotic Bcl-2 gene codes for a 25-kDa protein maintain organelle integrity and prevent the release of cytochrome c from mitochondria.…”