Preconditioning of bovine endothelial cells. The protective effect is mediated by an adenosine A2 receptor through a protein kinase C signaling pathway.
Preconditioning of bovine endothelial cells. The protective effect is mediated by an adenosine A2 receptor through a protein kinase C signaling pathway.
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牛内皮细胞的预处理。
DOI：
10.1161/01.res.78.1.73
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发表时间：
1996
影响因子：
20.1
通讯作者：
Ashraf,M
中科院分区：
文献类型：
--
作者：
Zhou,X;Zhai,X;Ashraf,M
我们验证了缺氧预处理可以保护冠状动脉内皮细胞免受缺氧和复氧损伤的假设，并且这种预处理作用可以通过腺苷A2受体通过蛋白激酶C（PKC）途径介导。将细胞用10分钟缺氧和10分钟复氧预处理，然后经受缺氧60分钟，接着复氧120分钟。在某些组中，8-磺苯茶碱（SPT [50 μmol/L]，一种非选择性腺苷受体拮抗剂）或calphostin C（100 nmol/L，一种PKC抑制剂）可阻断预处理效应。在其他组中，2-p-（2-羧乙基）苯乙氨基-5 ′-N-乙基甲酰氨基腺苷（CGS-21680 [20 nmol/L]，腺苷A2受体激动剂），R-（−）-N6-（2-苯异丙基）腺苷（R-PIA [50 nmol/L]，腺苷A1受体激动剂）或4β-佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA [100 nmol/L]，PKC激活剂）作为预处理以模拟预处理效应。用100 nmol/L calphostin C预处理内皮细胞，观察PKC抑制剂能否阻断CGS-21680激活腺苷A2受体对缺氧/复氧损伤的影响。预处理减少LDH释放，增加腺苷释放，促进PKC从胞浆到膜的转位，增加细胞活力，并保持ATP含量和细胞形态。用CGS-21680或PMA预处理导致与缺氧预处理类似的保护作用。该保护作用可被SPT或calphostin C完全阻断。结果提示：（1）心肌预处理对冠状动脉内皮细胞缺氧复氧损伤具有保护作用，（2）这种保护作用可能是通过激活腺苷A2受体介导的，（3）保护内皮细胞可能是心肌预处理的机制之一。
We tested the hypothesis that anoxic preconditioning could protect coronary endothelial cells against anoxic and reoxygenation injury and that this preconditioning effect could be mediated by an adenosine A2receptor via the protein kinase C (PKC) pathway. Cells were preconditioned with 10-minute anoxia and 10-minute reoxygenation and were then subjected to anoxia for 60 minutes, followed by 120 minutes of reoxygenation. In some groups, the preconditioning effect was prevented by 8-sulfophenyltheophylline (SPT [50 μmol/L], a nonselective adenosine receptor antagonist) or calphostin C (100 nmol/L, a PKC inhibitor). In other groups, 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS-21680 [20 nmol/L], an adenosine A2receptor agonist),R-(−)-N6-(2-phenylisopropyl)-adenosine (R-PIA [50 nmol/L], an adenosine A1receptor agonist), or 4β-phorbol 12-myristate 13-acetate (PMA [100 nmol/L], a PKC activator) was given as a pretreatment to mimic the preconditioning effect. Endothelial cells were also pretreated with 100 nmol/L calphostin C to confirm whether inhibition of PKC can block the effects of adenosine A2receptor activation by CGS-21680 on anoxia and reoxygenation injury. Preconditioning reduced LDH release, increased adenosine release, promoted translocation of PKC from cytosol to membrane, increased cell viability, and preserved ATP content and cell morphology. Pretreatment with either CGS-21680 or PMA resulted in protection similar to that seen with anoxic preconditioning. The protection was totally abolished by SPT or calphostin C. The results suggest that (1) preconditioning protects coronary endothelial cells against anoxia and reoxygenation injury, (2) the protection is probably mediated by activation of adenosine A2receptors through the PKC pathway, and (3) the preservation of endothelial cells may be one of the mechanisms of myocardial preconditioning.