Response of the Sirtuin/PXR signaling pathway in Mugilogobius chulae exposed to environmentally relevant concentration Paracetamol

Xie, Ming; Wang, Yimeng; Wang, Chao; Tang, Tianli; Li, Jianjun; Peng, Ying; Nie, Xiaoqin

doi:10.1016/j.aquatox.2022.106222

Cited by 3 publications

(2 citation statements)

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“…Playing a key role in this chemical defense system in fish is P-gp, which operates in tandem with other defense components. Fish tissues commonly express P-gp alongside other transporters and enzymes, including phase I functionalization enzymes (e.g., cytochrome 450 oxidases), phase II conjugating enzymes (e.g., glutathione S-transferase, sulfotransferase, UDP-glucuronosyltransferase) [75,[92][93][94][95], phase III exporters (e.g., multidrug resistance proteins [MRPs], breast cancer resistance protein [BCRP]) [41,75,93,96]), and solute carrier (SLC) transporters (e.g., organic anion transporting polypeptides [OATPs], organic anion transporters [OATs], organic cation transporters [OCTs], and multidrug and toxin extrusion proteins [MATEs]) [53,97,98]. Although the ABCB (MDR, P-gp) and ABCC (MRP) families of transporters are both referred to as "multidrug resistance proteins", they are distinct classes of transporters that perform different functions in the chemical defense system.…”

Section: P-glycoprotein In the Chemical Defense Systemmentioning

confidence: 99%

“…In fish, PXR has been identified as a central regulator of P-gp expression [103,104]. Studies have shown that PXR activation by xenobiotics, including pharmaceuticals (e.g., paracetamol, simvastatin) and plant flavonoids (e.g., quercetin, rotenone), leads to the upregulation of P-gp expression in fish tissues [95,142,143]. Similarly, Nrf2 activation has been linked to the regulation of P-gp in both fish and mammals [94,144].…”

Section: The Regulation Of P-glycoprotein Expressionmentioning

confidence: 99%

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A Review of P-Glycoprotein Function and Regulation in Fish

Johnston,

Kennedy

2024

Fishes

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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.

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