Mechanism of ischemic preconditioning mediated by protein kinase C activation caused by ischemia-related lipid metabolites.

缺血相关脂质代谢物引起的蛋白激酶C激活介导的缺血预处理机制。

基本信息

批准号：
08457014
负责人：
ARITA Makoto
金额：
$ 4.67万
依托单位：
Oita Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

1. Adenosine plays a crucial role in the evolution of ischemic preconditioning. With the use of microdialysis teci-miques in in situ rat hearts, we assessed the activity of ecto-5'-nucleotidase (a key enzyme responsible for adenosine production), and examined the effects of lysophosphatidyicholine (LPC) on the production of interstitial adenosine.2. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts and perfused with Tyrode solution containing adenosine 5'-monophosphate (AMP, 100 muM). With this system, the dialysate adenosine was considered to originate from the dephosphorylation of AMP, catalyzed by endogenous ecto-5'-nucleotidase, and the level of dialysate adenosine was verified to be a handy measure of the ecto-5'-nucleotidase activity in VIVO.3. LPC at concentrations of 25 and 50 muM significantly increased the level of dialysate adenosine to 122.7 * 4.3 % (n=4, p<O.05) and 158.6 * 7.2 % (n=5, p<O.O5) of the control value, respectively. Chelerythrine (200 muM), a protein kinase C (PKC) inhibitor, completely abolished the increase of dialysate adenosine afforded by LPC (50 muM) (n=5).4. These data provide the first evidence that LPC does increase the concentration of interstitial adenosine via the PKC-mediated activation of endogenous ecto-5'-nucleotidase, in in situ rat hearts.5. Thus, it is suggested that LPC accumulated in ischemic region plays a role for evolution of ischemic preconditioning via increased interstitial concentration of adenosine, a key compound responsible for ischemic preconditioning.

1. 腺苷在缺血预处理的演变中起着至关重要的作用。通过在原位大鼠心脏中使用微透析技术，我们评估了 5'-核苷酸酶（负责腺苷生成的关键酶）的活性，并检查了溶血磷脂酰胆碱 (LPC) 对间质腺苷生成的影响.2.将微透析探针植入麻醉大鼠心脏的左心室心肌中，并用含有5'-单磷酸腺苷（AMP，100μM）的Tyrode溶液灌注。通过该系统，透析液腺苷被认为源自内源性 5'-核苷酸酶催化的 AMP 去磷酸化，并且透析液腺苷水平被证实可以方便地测量体内 5'-核苷酸酶的活性。体内.3。浓度为 25 和 50 muM 的 LPC 使透析液腺苷水平显着增加至对照的 122.7 * 4.3 % (n=4, p<O.05) 和 158.6 * 7.2 % (n=5, p<O.O5)值，分别。 Chelerythrine (200 muM) 是一种蛋白激酶C (PKC) 抑制剂，完全消除了LPC (50 muM) 引起的透析液腺苷增加(n=5)。4。这些数据提供了第一个证据，表明 LPC 确实通过 PKC 介导的内源 ecto-5'-核苷酸酶的激活增加原位大鼠心脏中间质腺苷的浓度。 5．因此，表明在缺血区域积累的LPC通过增加间质腺苷浓度（负责缺血预处理的关键化合物）在缺血预处理的进化中发挥作用。