A Review of P-Glycoprotein Function and Regulation in Fish
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Fishes |
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| Online Access: | https://www.mdpi.com/2410-3888/9/2/51 |
| _version_ | 1827343631170666496 |
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| author | Christina U. Johnston Christopher J. Kennedy |
| author_facet | Christina U. Johnston Christopher J. Kennedy |
| author_sort | Christina U. Johnston |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T22:33:03Z |
| format | Article |
| id | doaj.art-e4e2a8dda59b482ab73bbe7a436bd2dc |
| institution | Directory Open Access Journal |
| issn | 2410-3888 |
| language | English |
| last_indexed | 2024-03-07T22:33:03Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Fishes |
| spelling | doaj.art-e4e2a8dda59b482ab73bbe7a436bd2dc2024-02-23T15:16:06ZengMDPI AGFishes2410-38882024-01-01925110.3390/fishes9020051A Review of P-Glycoprotein Function and Regulation in FishChristina U. Johnston0Christopher J. Kennedy1Department of Biological Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, CanadaDepartment of Biological Sciences, Simon Fraser University, Burnaby, BC V5A 1S6, CanadaThe 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.https://www.mdpi.com/2410-3888/9/2/51P-glycoproteinchemosensitizermultixenobiotic resistancefish |
| spellingShingle | Christina U. Johnston Christopher J. Kennedy A Review of P-Glycoprotein Function and Regulation in Fish Fishes P-glycoprotein chemosensitizer multixenobiotic resistance fish |
| title | A Review of P-Glycoprotein Function and Regulation in Fish |
| title_full | A Review of P-Glycoprotein Function and Regulation in Fish |
| title_fullStr | A Review of P-Glycoprotein Function and Regulation in Fish |
| title_full_unstemmed | A Review of P-Glycoprotein Function and Regulation in Fish |
| title_short | A Review of P-Glycoprotein Function and Regulation in Fish |
| title_sort | review of p glycoprotein function and regulation in fish |
| topic | P-glycoprotein chemosensitizer multixenobiotic resistance fish |
| url | https://www.mdpi.com/2410-3888/9/2/51 |
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