A Review of P-Glycoprotein Function and Regulation in Fish

被引:2
作者
Johnston, Christina U. [1 ]
Kennedy, Christopher J. [1 ]
机构
[1] Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
P-glycoprotein; chemosensitizer; multixenobiotic resistance; fish; MULTIXENOBIOTIC RESISTANCE MECHANISM; TROUT ONCORHYNCHUS-MYKISS; KILLIFISH FUNDULUS-HETEROCLITUS; ABC EFFLUX TRANSPORTERS; BLOOD-BRAIN-BARRIER; GENE-EXPRESSION ANALYSIS; PXR SIGNALING PATHWAY; ACID-BASE REGULATION; MULTIDRUG-RESISTANCE; DRUG TRANSPORTERS;
D O I
10.3390/fishes9020051
中图分类号
S9 [水产、渔业];
学科分类号
0908 ;
摘要
The teleost ATP Binding Cassette (ABC) transporter P-glycoprotein (P-gp) is an active transmembrane transporter that plays a pivotal role in facilitating the movement of both endogenous and xenobiotic substrates (moderately hydrophobic and amphipathic compounds) across cell membranes. P-gp exhibits substrate specificity often shared with other ABC transporters and solute carrier proteins, thereby ensuring the maintenance of chemical homeostasis within cells. These transporters are integral to chemical defense systems in fish, as they actively expel a wide range of substrates, primarily unmodified compounds, from cells. This transport process assists in preventing chemical absorption (e.g., intestine), safeguarding sensitive tissues (e.g., brain and gonads), and effectively excreting substances (e.g., liver and kidney). Upregulated P-gp export activity in aquatic animals results in the multi-xenobiotic resistance (MXR) phenotype that plays an essential protective role in survival in contaminated environments. Pollutants inhibiting P-gp are termed chemosensitizers and heighten fish sensitivity to toxic P-gp substrates. While the known intrinsic functions of P-gp in fish encompass steroid hormone and bile acid processing, relatively little attention has been given to endogenous substrates and inhibitors. Fish P-glycoprotein regulation is orchestrated by pivotal nuclear transcription factors, including pregnane X receptor (PXR) and nuclear factor erythroid 2-related factor 2 (Nrf2). This comprehensive review provides profound insights into P-gp's significance across diverse fish species, contributing to an enhanced understanding of fish physiology, evolution, and toxicology, and provides information with potential applications, such as environmental monitoring.
引用
收藏
页数:28
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