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MDR1 将在高海拔缺氧环境下的药代动力学变化及其潜在的调控网络中发挥关键作用。

MDR1 will play a key role in pharmacokinetic changes under hypoxia at high altitude and its potential regulatory networks.

机构信息

Key Laboratory of the Plateau Environmental Damage Control, Lanzhou General Hospital of Lanzhou Military Command , PLA, Lanzhou , China .

出版信息

Drug Metab Rev. 2015 May;47(2):191-8. doi: 10.3109/03602532.2015.1007012. Epub 2015 Feb 2.

Abstract

Some newest studies indicated that drug transports may play the key role in pharmacokinetics changes under hypoxia at high altitude; MDR1 is now known to affect the disposition of many administered drugs and make a major contribution to absorption, distribution, metabolism, excretion. Different expression of MDR1 is frequently found in different normal tissues and tumor cells; it is important to better understand how MDR1 is regulated under hypoxia, which seems to be a complex and highly controlled process. Several signaling pathways and transcription factors have been described as being involved in the regulation of MDR1 expression, such as MAPK/ERK, nuclear factor-kappaB, hypoxia-inducible factor-1a, pregnane × receptor, constitutive androstane receptor and microRNA. Recently, researches have been increasingly appreciating long non-coding RNAs (lncRNAs) as an integral component of gene regulatory networks. lncRNAs play crucial roles in various biological processes ranging from epigenetic gene regulation, transcriptional control, post-transcriptional regulation, pre-mRNA processing and nuclear organization. A last recent research showed that H19 gene non-coding RNA is believed to induce P-glycoprotein expression under hypoxia.

摘要

一些最新的研究表明,药物转运体可能在高原缺氧条件下的药代动力学变化中发挥关键作用;MDR1 现已被证实影响许多给予药物的处置,并对吸收、分布、代谢和排泄有重要贡献。MDR1 在不同的正常组织和肿瘤细胞中的表达不同;更好地了解 MDR1 在缺氧下是如何调节的非常重要,这似乎是一个复杂和高度受控的过程。已经描述了几种信号通路和转录因子参与 MDR1 表达的调节,如 MAPK/ERK、核因子-κB、缺氧诱导因子-1a、孕烷 X 受体、组成型雄烷受体和 microRNA。最近,研究人员越来越认识到长非编码 RNA(lncRNA)是基因调控网络的一个组成部分。lncRNA 在从表观遗传基因调控、转录控制、转录后调控、前体 mRNA 处理和核组织等各种生物学过程中发挥着关键作用。最近的一项研究表明,H19 基因非编码 RNA 被认为在缺氧下诱导 P-糖蛋白表达。

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