• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Life sciences >Evaluation of cytochrome P450 4 family as mediator of phospholipase D activation in aortic vascular smooth muscle cells.
【24h】

Evaluation of cytochrome P450 4 family as mediator of phospholipase D activation in aortic vascular smooth muscle cells.

机译：评估细胞色素P450 4家族作为主动脉血管平滑肌细胞中磷脂酶D激活的介体。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Norepinephrine (NE) stimulates phospholipase D (PLD) activity via phospholipase A(2)-dependent arachidonic acid release in rabbit aortic vascular smooth muscle cells (VSMC). We have previously shown that exogenous 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid generated through the cytochrome P450 (CYP) 4A pathway in vivo, stimulates PLD activity. Whether endogenous CYP4-derived arachidonic acid metabolites act as intracellular mediators of NE-induced PLD activation in VSMC is not known. In rabbit aortic VSMC, prototypical hepatic/renal CYP4A inducers such as fenofibrate and Wy 14643 inhibited both basal and NE-induced PLD activity after 48 h of exposure. The level of CYP4F, and to a lesser extent CYP4A, was also decreased by these agents. The expression levels of rabbit aortic VSMC CYP4A and CYP4F isoforms were reduced by antisense oligonucleotides treatment for 48 hours as measured by RTQ-PCR or Western blotting. This reduction in CYP4A or CYP4F levels did not change NE-induced PLD activation. The corresponding CYP4A scrambled and CYP4F sense oligonucleotides did not alter CYP levels. PLD activity was increased by ~70% after 15 min of stimulation with NE, whereas lauric acid omega-hydroxylase activity, a measure of fatty acid omega-hydroxylation, was unchanged. Inhibition of omega-hydroxylation with DDMS and HET0016, selective omega-hydroxylase inhibitors, and 20-HEDE, an antagonist of 20-HETE, increased PLD activity in a concentration-dependent manner and did not alter NE-induced PLD activation. These data suggest that PLD activation by NE is independent of the CYP4A/4F enzymes in rabbit aortic VSMC.
机译：去甲肾上腺素（NE）通过磷脂酶A（2）依赖的花生四烯酸释放在兔主动脉血管平滑肌细胞（VSMC）中刺激磷脂酶D（PLD）活性。我们以前已经表明，外源性20-羟基二十碳四烯酸（20-HETE）是一种通过体内细胞色素P450（CYP）4A途径产生的类花生酸，可刺激PLD活性。尚不清楚内源性CYP4衍生的花生四烯酸代谢物是否在VSMC中充当NE诱导的PLD活化的细胞内介质。在兔主动脉VSMC中，原型肝/肾CYP4A诱导剂（如非诺贝特和Wy 14643）在暴露48小时后同时抑制基础和NE诱导的PLD活性。这些药物还降低了CYP4F的水平，并在较小程度上降低了CYP4A的水平。通过RTQ-PCR或Western blotting检测，通过反义寡核苷酸处理48小时，兔主动脉VSMC CYP4A和CYP4F同工型的表达水平降低。 CYP4A或CYP4F水平的这种降低不会改变NE诱导的PLD激活。相应的CYP4A和CYP4F有义寡核苷酸没有改变CYP水平。用NE刺激15分钟后，PLD活性增加了约70％，而月桂酸ω-羟化酶活性（脂肪酸ω-羟化的量度）没有变化。用DDMS和HET0016（选择性的ω-羟化酶抑制剂）和20-HEDE（20-HETE的拮抗剂）抑制ω-羟基化，以浓度依赖的方式增加PLD活性，并且不会改变NE诱导的PLD激活。这些数据表明NE激活的PLD独立于兔主动脉VSMC中的CYP4A / 4F酶。

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