EVIDENCE THAT TRANSLOCATION OF PROTEIN-KINASE-C IS A KEY EVENT DURING ISCHEMIC PRECONDITIONING OF RABBIT MYOCARDIUM
EVIDENCE THAT TRANSLOCATION OF PROTEIN-KINASE-C IS A KEY EVENT DURING ISCHEMIC PRECONDITIONING OF RABBIT MYOCARDIUM
复制标题
DOI：
10.1006/jmcc.1994.1078
复制
发表时间：
1994-05-01
影响因子：
5
通讯作者：
DOWNEY, JM
中科院分区：
文献类型：
--
作者：
LIU, YG;YTREHUS, K;DOWNEY, JM
我们使用了三种干预措施来严格检验这一理论，即缺血预适应是胞浆蛋白激酶C(PKC)移位到可被激活的细胞膜中的结果。如果这一理论是正确的，那么在预适应缺血期间，激酶活性不应该是必要的，因此在这个时候阻止激酶活性应该不会阻止保护。其次，由于细胞内的大多数转位过程是由细胞骨架微管完成的，用秋水仙碱破坏它们也应该阻止预适应的保护作用。最后，通过短暂暴露于PMA来移位PKC，应该仍然需要腺苷受体激活，以在随后的缺血期间重新激活PKC途径。在30分钟损伤期间用星形孢子素阻断激酶活性可完全阻断预适应心脏的保护作用，但当星形孢子素治疗仅限于预适应发作时，在所研究的8个心脏中有5个心脏的保护作用没有被阻断。用秋水仙碱破坏微管确实阻断了预适应的保护作用(38.3±1.9%的梗死率比40.6±4.1%的非预适应时)。秋水仙碱对非预适应组的脑梗塞面积无影响。局部缺血30min时，PMA处理5min+洗脱10min可显著缩小心肌梗死范围(对照组为5.9±1.1%v31±3.5%)。加入腺苷受体阻滞剂可阻断PMA的保护作用。持续缺血期(38.1±6.1%)。这三个实验都有力地支持了缺血预适应的易位学说。
We used three interventions to test critically the theory that ischemic preconditioning is the result of translocation of cytosolic protein kinase C (PKC) into the membranes where it can be activated. If that theory were true then kinase activity should not be necessary during the preconditioning ischemia and thus blocking kinase activity at this time should not block protection. Secondly, since most translocation processes in the cell are accomplished by cytoskeletal microtubules, disrupting them with colchicine should also block protection from preconditioning. Finally, translocating PKC by transient exposure to PMA, should still require adenosine receptor activation to reactivate the PKC pathway during the subsequent ischemia. Blocking kinase activity with staurosporine during a 30 min insult completely blocks protection in preconditioned hearts but when staurosporine treatment was confined to the preconditioning episode protection was not blocked in five of the eight hearts studied. Microtubule disruption with colchicine did block the protective effect of preconditioning (38.3±1.9% infarctionv40.6±4.1% in non-preconditioned). Colchicine had no effect on infarct size in the non-preconditioned group. Five min PMA treatment plus 10 min washout significantly limited infarct size in isolated rabbit hearts subjected to 30 min regional ischemia (5.9±1.1%v31±3.5% infarction in control). PMA's protection was blocked by adding the adenosine receptor blocker. SPT, during the sustained ischemia (38.1 ± 6.1% infarction). All three of these experiments strongly support the translocation theory of ischemic preconditioning.