Pyrrolidinyl caffeamide against ischemia/reperfusion injury in cardiomyocytes through AMPK/AKT pathways.
Pyrrolidinyl caffeamide against ischemia/reperfusion injury in cardiomyocytes through AMPK/AKT pathways.
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DOI：
10.1186/s12929-015-0125-3
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发表时间：
2015-03-18
影响因子：
11
通讯作者：
Su MJ
中科院分区：
文献类型：
--
作者：
Lee SY;Ku HC;Kuo YH;Chiu HL;Su MJ
冠心病是世界上主要的死亡原因，仍然需要治疗以减少伤害。在心肌缺血/再灌注损伤中，糖酵解和葡萄糖氧化的解偶联导致乳酸积聚。细胞死亡发生，最终导致心肌梗死。咖啡酸是自然界中的主要酚类成分之一，具有抗氧化剂的作用。本课题组合成了一种新型咖啡酸衍生物--吡咯烷基咖啡酰胺(PLCA)。本实验旨在探讨PLCA对新生大鼠心肌细胞缺氧/复氧(H/R)和心肌I/R的影响。分离心肌细胞，缺氧6h，再灌流18h。低氧开始前加入聚乳酸(0.1~3μM)和二甲双胍(30μM)。在细胞和动物模型中，1μM的PLCA和30μM的二甲双胍在提高细胞存活率和减轻细胞凋亡方面具有相似的作用，PLCA促进p-AMPK、p-AKT和GLUT4的上调，从而诱导心肌保护作用。PLCA可减轻心肌I/R期间心肌乳酸的蓄积，且PLCA(1 mg/kg)组的心肌梗死面积小于咖啡酸(1 mg/kg)组。AMPK和AKT被PLCA协同激活，促进葡萄糖的利用，从而减少乳酸的积累和细胞的死亡。PLCA的心脏保护剂量低于二甲双胍和咖啡酸。我们为这种治疗心肌I/R损伤的潜在药物提供了一个新的视角。
Coronary heart disease is a leading cause of death in the world and therapy to reduce injury is still needed. The uncoupling of glycolysis and glucose oxidation induces lactate accumulation during myocardial ischemia/reperfusion (I/R) injury. Cell death occurs and finally leads to myocardial infarction. Caffeic acid, one of the major phenolic constituents in nature, acts as an antioxidant. Pyrrolidinyl caffeamide (PLCA), a new derivative of caffeic acid, was synthesized by our team. We aimed to investigate the effect of PLCA on hypoxia/reoxygenation (H/R) in neonatal rat ventricular myocytes (NRVM) and on myocardial I/R in rats. Cardiomyocytes were isolated and subjected to 6 h hypoxia followed by 18 h reperfusion. PLCA (0.1 to 3 μM) and metformin (30 μM) were added before hypoxia was initiated. PLCA at 1 μM and metformin at 30 μM exerted similar effects on the improvement of cell viability and the alleviation of cell apoptosis in NRVM after H/R. PLCA promoted p-AMPK, p-AKT, and GLUT4 upregulation to induce a cardioprotective effect in both cell and animal model. The accumulation of cardiac lactate was attenuated by PLCA during myocardial I/R, and infarct size was smaller in rats treated with PLCA (1 mg/kg) than in those treated with caffeic acid (1 mg/kg). AMPK and AKT are synergistically activated by PLCA, which lead facilities glucose utilization, thereby attenuating lactate accumulation and cell death. The cardioprotective dose of PLCA was lower than those of metformin and caffeic acid. We provide a new insight into this potential drug for the treatment of myocardial I/R injury.
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影响因子：
9.8
作者：
Kumaran, K. Senthil;Prince, P. Stanely Mainzen
通讯作者：
Prince, P. Stanely Mainzen
影响因子：
4.8
作者：
Liu, Chao;Liang, Bin;Zou, Ming-Hui
通讯作者：
Zou, Ming-Hui
影响因子：
--
作者：
MANCHESTER, J;KONG, XM;LAWRENCE, JC
通讯作者：
LAWRENCE, JC
影响因子：
37.8
作者：
Goncharov DA;Kudryashova TV;Ziai H;Ihida-Stansbury K;DeLisser H;Krymskaya VP;Tuder RM;Kawut SM;Goncharova EA
通讯作者：
Goncharova EA
影响因子：
3.6
作者：
Ku, Hui-Chun;Chen, Wen-Pin;Su, Ming-Jai
通讯作者：
Su, Ming-Jai