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

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.

• Drug transports
• high altitude
• MDR1
• pharmacokinetics
• regulatory networks

Acknowledgements

The author appreciates the contribution of Lin Yang in the preparation of this manuscript.

Declaration of interest

This article is original, has been written by the stated authors who are all aware of its content and approve its submission. It has not been published previously, it is not under consideration for publication elsewhere, no conflict of interest exists. The article will not be published elsewhere in the same form, in any language, without the written consent of the publisher.