C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling
C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling
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DOI：
10.1152/ajpheart.01072.2005
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发表时间：
2006-05-01
影响因子：
4.8
通讯作者：
Kuppusamy, P
中科院分区：
文献类型：
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作者：
Khan, M;Varadharaj, S;Kuppusamy, P
我们以前的研究表明，C-藻蓝蛋白（PC），一种抗氧化胆蛋白色素的螺旋藻（蓝绿色），有效地抑制阿霉素诱导的氧化应激和心肌细胞凋亡。在离体Langendorff心脏灌流模型中，我们研究了PC对缺血再灌注（I/R）诱导的心肌损伤的保护作用。将大鼠心脏在37 ℃下进行30分钟的全脑缺血，然后进行45分钟的再灌注。在缺血开始前和整个再灌注过程中，用PC（10 μ M）或螺旋藻制剂（SP，50 mg/l）灌注心脏15分钟。再灌注45分钟后，未处理的（对照）心脏显示冠状动脉流量（44%）、左心室发展压力（21%）和心率-压力乘积（24%）的恢复显著降低，冠状动脉流出液中乳酸脱氢酶和肌酸激酶的释放增加，明显的心肌梗死（44%的危险区），和TdT介导的dUTP缺口末端标记阳性凋亡细胞与缺血前状态相比。PC或SP可明显促进心功能恢复，缩小梗死面积，减少乳酸脱氢酶和肌酸激酶释放，抑制I/R诱导的自由基产生。PC逆转I/R诱导的p38 MAPK、Bax和caspase-3的活化，Bcl-2的抑制，以及TdT介导的dUTP缺口末端标记阳性凋亡细胞的增加。然而，I/R也诱导ERK 1/2的激活，PC处理增强。总的来说，这些结果首次表明，PC衰减I/R诱导的心功能障碍，通过其抗氧化和抗凋亡作用和p38 MAPK和ERK 1/2的调制。
We previously showed that C-phycocyanin (PC), an antioxidant biliprotein pigment of Spirulina platensis (a blue-green alga), effectively inhibited doxorubicin-induced 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 degrees C followed by 45 min of reperfusion. Hearts were perfused with PC (10 mu 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 label-positive 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.