Expression and Function of ABC Proteins in Fish Intestine

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 9, 2021

In fish, the intestine is fundamental for digestion, nutrient absorption, and other functions like osmoregulation, acid-base balance, excretion of some metabolic products. These require a large exchange surface area, which, in turn, favors absorption natural anthropogenic foreign substances (xenobiotics) either dissolved water or contained food. According to their chemical nature, nutrients, ions, may cross epithelium cells’ apical basolateral membranes by passive diffusion through wide array transport proteins also endocytosis exocytosis. same way, xenobiotics can this barrier taking advantage that physiological substrates. The entry toxic counterbalanced an active efflux mediated diverse membrane proteins, including ATP binding cassette (ABC) proteins. Recent advances structure, molecular properties, functional studies have shed light on importance these cellular organismal homeostasis. There abundant literature mammalian ABC while fish mainly focused liver and, minor degree, kidney organs. Despite critical normal physiology as prevent incorporation, intestine’s transporters received much less attention. All subfamilies are present intestine, although functionality still scarcely studied. For example, there few ABC-mediated made with polarized intestinal preparations. Thus, only works discriminate from activity. We briefly describe main each subfamily reported mammals organs help understand roles intestine. Our study considers immunohistochemical, histological, biochemical, molecular, physiological, toxicological aspects focus most extensively studied (subfamilies ABCB, ABCC, ABCG), considering location distribution along discuss implication substrates aquatic pollutants, such pesticides, cyanotoxins, metals, hydrocarbons, pharmaceutical

Language: Английский

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Effects of Benzo[k]fluoranthene at Two Temperatures on Viability, Structure, and Detoxification-Related Genes in Rainbow Trout RTL-W1 Cell Spheroids

Toxics, Journal Year: 2025, Volume and Issue: 13(4), P. 302 - 302

Published: April 12, 2025

Polycyclic aromatic hydrocarbons (PAHs) and global warming impact aquatic ecosystems, eventually interacting. Monolayer (2D) cultures of cell lines, such as the rainbow trout liver RTL-W1, are employed for unveiling toxicological effects in fish. Nonetheless, three-dimensional (3D) models constitute an alternate paradigm, better emulating vivo responses. Here, ultra-low attachment (ULA) plates were used to generate ten-day-old RTL-W1 spheroids exposure a control, solvent control (0.1% DMSO) model PAH benzo[k]fluoranthene (BkF) at 10 100 nM 18 23 °C (thermal stress). After 4-day exposure, analyzed viability (alamarBlue lactate dehydrogenase), biometry (area, diameter sphericity), histocytology (optical electron microscopy), mRNA levels detoxification-related genes cytochrome P450 (CYP)1A, CYP3A27, aryl hydrocarbon receptor (AhR), glutathione S-transferase (GST), uridine diphosphate–glucuronosyltransferase (UGT), catalase (CAT), multidrug resistance-associated protein 2 (MRP2) bile salt export (BSEP). Immunocytochemistry (ICC) was assess CYP1A expression. Neither temperature nor BkF altered spheroids’ or biometry. modified cell’s ultrastructure. The expression augmented with both concentrations, while AhR’s increased higher concentration. showed dose-dependent increase. Temperature concurrently modelled UGT’s expression, which condition °C. Conversely, MRP2, BSEP expressions lowered CAT GST uninfluenced by either stressor. Overall, impacted independently interactively spheroids. These seem be useful novel tools studying liver-related PAHs.

Language: Английский

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Gill and Liver Transcript Expression Changes Associated With Gill Damage in Atlantic Salmon (Salmo salar)

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 28, 2022

Gill damage represents a significant challenge in the teleost fish aquaculture industry globally, due to gill's involvement several vital functions and direct contact with surrounding environment. To examine local systemic effects accompanying gill (which is likely negatively affect function) of Atlantic salmon, we performed field sampling collect liver tissue after environmental insults (e.g., harmful algal blooms). Before sampling, gills were visually inspected was scored; scores assigned from pristine [gill score 0 (GS0)] severely damaged (GS3). Using 44K salmonid microarray platform, aimed compare transcriptomes moderately (i.e., GS2) tissue. Rank Products analysis (5% percentage false-positives) identified 254 34 upregulated downregulated probes, respectively, GS2 compared GS0. Differentially expressed probes represented genes associated including remodeling, wound healing, stress immune responses. We qPCR for all four using microarray-identified other damage-associated biomarker genes. Transcripts related healing

Language: Английский

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Toxicological effects of chemical pesticides in fish: Focusing on intestinal injury and gut microbial dysbiosis

Pesticide Biochemistry and Physiology, Journal Year: 2025, Volume and Issue: 211, P. 106405 - 106405

Published: April 9, 2025

Language: Английский

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A Review of P-Glycoprotein Function and Regulation in Fish

Fishes, Journal Year: 2024, Volume and Issue: 9(2), P. 51 - 51

Published: Jan. 27, 2024

The teleost ATP Binding Cassette (ABC) transporter P-glycoprotein (P-gp) is an active transmembrane that plays a pivotal role in facilitating the movement of both endogenous and xenobiotic substrates (moderately hydrophobic amphipathic compounds) across cell membranes. P-gp exhibits substrate specificity often shared with other ABC transporters solute carrier proteins, thereby ensuring maintenance chemical homeostasis within cells. These are integral to defense systems fish, as they actively expel wide range substrates, primarily unmodified compounds, from This transport process assists preventing absorption (e.g., intestine), safeguarding sensitive tissues brain gonads), effectively excreting substances liver kidney). Upregulated export activity aquatic animals results multi-xenobiotic resistance (MXR) phenotype essential protective survival contaminated environments. Pollutants inhibiting termed chemosensitizers heighten fish sensitivity toxic substrates. While known intrinsic functions encompass steroid hormone bile acid processing, relatively little attention has been given inhibitors. Fish regulation orchestrated by nuclear transcription factors, including pregnane X receptor (PXR) factor erythroid 2-related 2 (Nrf2). comprehensive review provides profound insights into P-gp’s significance diverse species, contributing enhanced understanding physiology, evolution, toxicology, information potential applications, such environmental monitoring.

Language: Английский

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17α-Ethynylestradiol and Levonorgestrel Exposure of Rainbow Trout RTL-W1 Cells at 18 °C and 21 °C Mainly Reveals Thermal Tolerance, Absence of Estrogenic Effects, and Progestin-Induced Upregulation of Detoxification Genes

Genes, Journal Year: 2024, Volume and Issue: 15(9), P. 1189 - 1189

Published: Sept. 10, 2024

Fish are exposed to increased water temperatures and aquatic pollutants, including endocrine-disrupting compounds (EDCs). Although each stressor can disturb fish liver metabolism independently, combined effects may exist. To unveil the molecular mechanisms behind of EDCs temperature, cell lines potential models needing better characterisation. Accordingly, we rainbow trout RTL-W1 cells (72 h), at 18 °C 21 °C, ethynylestradiol (EE2), levonorgestrel (LNG), a mixture both hormones (MIX) 10 µM. The gene expression selection targets related detoxification (CYP1A, CYP3A27, GST, UGT, CAT, MRP2), estrogen exposure (ERα, VtgA), lipid (FAS, FABP1, FATP1), temperature stress (HSP70b) was analysed by RT-qPCR. GST higher after LNG than °C. further enhanced while MIX expressions CYP3A27 MRP2. In contrast, FAS only in MIX, compared control. ERα, VtgA, CYP1A, HSP70b, FATP1 were not influenced or tested EDCs. model unresponsive EE2 alone, sensitive (in pathway genes), mainly insensitive range but had specific interactions.

Language: Английский

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A comparative study on targeted gene expression in zebrafish and its gill cell line exposed to chlorpyrifos

In Vitro Cellular & Developmental Biology - Animal, Journal Year: 2024, Volume and Issue: 60(4), P. 397 - 410

Published: April 1, 2024

Language: Английский

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Advances in drug resistance of osteosarcoma caused by pregnane X receptor

Drug Metabolism Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 14

Published: June 13, 2024

Osteosarcoma (OS) is a prevalent malignancy among adolescents, commonly manifesting during childhood and adolescence. It exhibits high degree of malignancy, propensity for metastasis, rapid progression, poses challenges in clinical management. Chemotherapy represents an efficacious therapeutic modality OS treatment. However, chemotherapy resistance major problem In order to treat effectively, it particularly important explore the mechanism OS.The Pregnane X receptor (PXR) nuclear primarily involved metabolism, transport, elimination xenobiotics, including chemotherapeutic agents. PXR involves three stages drug metabolism: stage I: metabolism enzymes; II: binding enzyme; III: transporter.PXR has been confirmed be process malignant tumors. The expression increased OS, which may related OS. Therefore, wereviewed detail role

Language: Английский

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A Step Forward in the Characterization of Primary Brown Trout Hepatocytic Spheroids as Experimental Models

Animals, Journal Year: 2023, Volume and Issue: 13(14), P. 2277 - 2277

Published: July 12, 2023

Mammal hepatocyte spheroids have been investigated as alternative experimental models in several contexts, since three-dimensional (3D) systems shown the potential to mimic vivo scenarios. The description of fish 3D is still minimal. This study intends further characterize brown trout primary at distinct time points up 25 days culture. Viability, biometry, histomorphology, and basal expression a selection genes (metabolism detoxification, efflux transport, estrogenic signalling) were considered. gene whole liver samples from same donor evaluated concurrently. After 12 culture, exhibited biometric morphological stability. From 12th 20th day levels for most selected did not vary. targeted mRNA higher compared spheroids. Despite that, data supported that this model resembles some features. As an model, it showed be used stable window can exploited exposure tests different xenobiotics, namely, compounds.

Language: Английский

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The Impact of Indoles Activating the Aryl Hydrocarbon Receptor on Androgen Receptor Activity in the 22Rv1 Prostate Cancer Cell Line

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 24(1), P. 502 - 502

Published: Dec. 28, 2022

The activation of the aryl hydrocarbon receptor (AhR) by xenobiotic compounds was demonstrated to result in degradation androgen (AR). Since prostate cancer is often dependent on AR, it has become a significant therapeutic target. As emerging concept bacterial mimicry, we tested whether with indole scaffolds capable AhR have potential restrict AR activity cells. Altogether, 22 indolic were tested, and all them activated AhR. However, only eight decreased DHT-induced luciferase activity. All indoles, which met AhR-activating AR-suppressing criteria, expression DHT-inducible target genes, specifically KLK3 FKBP5 mRNAs. reduced binding promoter confirmed chromatin immunoprecipitation (ChIP) assay. In addition, some indoles significantly protein mRNA level. By using CRISPR/Cas9 knockout technology, no relationship between measured as gene expression, observed. conclusion, that activate possess AR-inhibiting activity, seems be related downregulation rather than alone. Moreover, there does not seem clear would connect suppression 22Rv1

Language: Английский

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