...
首页> 外文期刊>Journal of pharmacological sciences. >Signaling pathways involved in the cardioprotective effects of cannabinoids.
【24h】

Signaling pathways involved in the cardioprotective effects of cannabinoids.

机译:涉及大麻素心脏保护作用的信号通路。

获取原文
获取原文并翻译 | 示例
           

摘要

The aim of the present article is to review the cardioprotective properties of cannabinoids, with an emphasis on the signaling pathways involved. Cannabinoids have been reported to protect against ischemia in rat isolated hearts, as well as in rats and mice in vivo. Although these effects have been observed mostly with a pre-treatment of a cannabinoid, we report that the selective CB(2)-receptor agonist JWH133 is able to reduce infarct size when administered either before ischemia, during the entire ischemic period, or just upon reperfusion. Little is known about the signaling pathways involved in these cardioprotective effects. Likely candidates include protein kinase C (PKC) and mitogen-activated protein kinases (MAPK) since they are activated during ischemia-reperfusion and contribute to the protective effect ischemic preconditioning. The use of pharmacological inhibitors suggests that PKC, p38 MAPK, and p42/p44 MAPK (ERK1/2) contribute to the protective effect of cannabinoids. In addition, perfusion with JWH133 in healthy hearts caused an increase in both p38 MAPK phosphorylation level and activity, whereas the CB(1)-receptor agonist ACEA was associated with an increase in the phosphorylation status of both ERK1 and ERK2 without any change in activity. During ischemia, both agonists doubled p38 MAPK activity, whereas ERK1/2 phosphorylation level and activity during reperfusion were enhanced only by the CB(1)-receptor agonist. Finally, although nitric oxide (NO) was shown to exert both pro and anti-apoptotic effects on cardiomyocytes, with an apparently controversial effect on myocardial survival, our data suggest that NO may contribute to the cardioprotective effect of some cannabinoids.
机译:本文的目的是回顾大麻素的心脏保护特性,重点是所涉及的信号传导途径。据报道,大麻素可预防离体大鼠心脏以及体内大鼠和小鼠的局部缺血。尽管这些作用主要是通过大麻素的预处理而观察到的,但我们报道选择性CB(2)-受体激动剂JWH133能够在缺血前,整个缺血期间或刚给药时减少梗死面积再灌注。关于这些心脏保护作用的信号传导途径知之甚少。可能的候选药物包括蛋白激酶C(PKC)和促分裂原激活的蛋白激酶(MAPK),因为它们在缺血再灌注过程中被激活并有助于缺血预处理的保护作用。药理抑制剂的使用表明,PKC,p38 MAPK和p42 / p44 MAPK(ERK1 / 2)有助于大麻素的保护作用。此外,在健康心脏中灌注JWH133会导致p38 MAPK磷酸化水平和活性均增加,而CB(1)-受体激动剂ACEA与ERK1和ERK2的磷酸化状态增加相关,而活性没有任何变化。在缺血期间,两种激动剂都使p38 MAPK活性增加了一倍,而ERK1 / 2磷酸化水平和再灌注过程中的活性仅由CB(1)-受体激动剂增强。最后,尽管一氧化氮(NO)对心肌细胞具有促凋亡和抗凋亡作用,但对心肌存活的作用却存在明显争议,但我们的数据表明NO可能有助于某些大麻素的心脏保护作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号