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。腺苷在缺血性预处理的进化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teci-riques，我们评估了源化5'-核苷酸酶（一种负责腺苷产生的关键酶）的活性，并检查了溶血磷脂二乙醇（LPC）对天质腺苷的生产的影响。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，100 MUM）的酪氨酸溶液灌注。使用该系统，透析腺苷腺苷被认为是由AMP的去磷酸化起源于AMP的去磷酸化，并由内源性ECTO-5'-核苷酸酶催化，并且证实了透析腺苷的水平，是对ECTO-5'-核苷酸酶活性的方便度量。浓度为25和50的LPC显着将透析腺苷的水平显着提高到122.7 * 4.3％（n = 4，p <o.05）和158.6 * 7.2％（n = 5，p <o5，p <o5），分别为控制值。 Chelerythrine（200 MUM）是一种蛋白激酶C（PKC）抑制剂，完全废除了LPC（50 MUM）提供的透析液腺苷的增加（n = 5）.4。这些数据提供了第一个证据，表明LPC确实通过原位大鼠心脏的PKC介导的内源性Ecto-5'-核苷酸酶的激活增加了间质性腺苷的浓度。5。因此，建议在缺血区域中积累的LPC通过增加腺苷的间隙浓度来进化是缺血性预处理的作用，腺苷的间隙浓度是造成缺血性预处理的关键化合物。