Two novel multidrug resistance associated protein (MRP/ABCC) from the Mediterranean mussel (Mytilus galloprovincialis): characterization and expression patterns in detoxifying tissues

2015 ◽  
Vol 93 (7) ◽  
pp. 567-578 ◽  
Author(s):  
V. Lozano ◽  
R. Martínez-Escauriaza ◽  
M.L. Pérez-Parallé ◽  
A.J. Pazos ◽  
J.L. Sánchez
Keyword(s):  
Multidrug Resistance ◽  
Digestive Gland ◽  
Okadaic Acid ◽  
Abc Transporters ◽  
Mytilus Galloprovincialis ◽  
Expression Patterns ◽  
Cancer Resistance ◽  
Mediterranean Mussel ◽  
The Mediterranean

Multidrug resistance associated proteins (MRP) belong to the ABCC branch of the ABC transporters. The MRP together with P-gp (P-glycoprotein; MDR1; ABCB1) and BCRP (breast cancer resistance protein; ABCG2) confer multixenobiotic resistance (MXR) in marine vertebrates. In aquatic invertebrates, little is known about the presence and role of these ABC transporters. The ABC transporters play an important role in the absorption, distribution, and excretion of drugs, xenobiotics, and endogenous compounds and are predominantly expressed in excretory organs. In the present study, we identified and characterized two MRP/ABCC transporters (mrp1 and mrp2) from the Mediterranean mussel (Mytilus galloprovincialis Lamarck, 1819). The two cDNAs finally obtained were 4648 bp for mrp1 and 5065 bp for mrp2 with open reading frames of 1500 and 1524 residues, respectively. Analysis of the amino acid sequences revealed the structural organization of ABC transporters with the typical and highly conserved motifs. The expression levels of these genes revealed that the highest expression of mrp1 and mrp2 genes was found in the digestive gland followed by gills, and the lowest expression of the three tissues was detected in the mantle. The expression of these genes was also studied in mussels naturally contaminated with okadaic acid (from a bloom of Dinophysis acuminata Claparède and Lachmann, 1859). The overexpression of mrp2 in the digestive gland suggests that this gene is involved in the process of detoxification of okadaic acid in M. galloprovincilais. These expression patterns agree with the suggested role of these genes in the protection against endogenous or exogenous compounds in aquatic organisms.

scholarly journals A Comparative Assessment of the Chronic Effects of Micro- and Nano-Plastics on the Physiology of the Mediterranean Mussel Mytilus galloprovincialis

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 649
Author(s):  
Marco Capolupo ◽  
Paola Valbonesi ◽  
Elena Fabbri
Keyword(s):  
Mytilus Galloprovincialis ◽  
Acetylcholinesterase Activity ◽  
Particle Sizes ◽  
Glutathione S Transferase ◽  
Phase Ii Metabolism ◽  
Chronic Effects ◽  
Mediterranean Mussel ◽  
Metabolism Enzyme ◽  
The Mediterranean

The ocean contamination caused by micro- and nano-sized plastics is a matter of increasing concern regarding their potential effects on marine organisms. This study compared the effects of a 21-day exposure to 1.5, 15, and 150 ng/L of polystyrene microplastics (PS-MP, 3-µm) and nanoplastics (PS-NP, 50-nm) on a suite of biomarkers measured in the Mediterranean mussel Mytilus galloprovincialis. Endpoints encompassed immunological/lysosomal responses, oxidative stress/detoxification parameters, and neurotoxicological markers. Compared to PS-MP, PS-NP induced higher effects on lysosomal parameters of general stress. Exposures to both particle sizes increased lipid peroxidation and catalase activity in gills; PS-NP elicited greater effects on the phase-II metabolism enzyme glutathione S-transferase and on lysozyme activity, while only PS-MP inhibited the hemocyte phagocytosis, suggesting a major role of PS particle size in modulating immunological/detoxification pathways. A decreased acetylcholinesterase activity was induced by PS-NP, indicating their potential to impair neurological functions in mussels. Biomarker data integration in the Mussel Expert System identified an overall greater health status alteration in mussels exposed to PS-NP compared to PS-MP. This study shows that increasing concentrations of nanoplastics may induce higher effects than microplastics on the mussel’s lysosomal, metabolic, and neurological functions, eventually resulting in a greater impact on their overall fitness.

scholarly journals The role of dietary flavonoids for modulation of ATP binding cassette transporter mediated multidrug resistance

eFood ◽  
2021 ◽  
Author(s):  
Hui Teng ◽  
Hongting Deng ◽  
Yuanju He ◽  
Qiyan Lv ◽  
Lei Chen
Keyword(s):  
Multidrug Resistance ◽  
Abc Transporters ◽  
Systemic Circulation ◽  
Atp Binding ◽  
Cancer Resistance ◽  
Associated Proteins ◽  
Food Toxin ◽  
Atp Binding Cassette

Flavonoids are widely existing compounds with enormous pharmacological effects from food and medicine. However, the low bioavailability in intestinal absorption and metabolism limits their clinical application. Intestinal efflux ABC (ATP binding cassette) transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs), act as "pumping doors" to regulate the efflux of flavonoids from intestinal epithelial cells into the intestinal cavity or the systemic circulation. The present review describes the critical effect of ABC transporters involved in the efflux of flavonoids which depend on its efflux direction. And the role of flavonoids for modulation of intestinal ABC transporters was emphasized and several examples were given. We summarized that the resistance effect of flavonoid-mediated multidrug on ABC transporters may influence the bioavailability of drugs, bioactive ingredients and/or toxic compounds upon dietary uptake. Meanwhile, flavonoids functionalized as reversing agents of the ABC transporter may be an important mechanism for unexpected food-drug, food-toxin or food-food interactions. The overview also indicates that elucidation of the action and mechanism of the intestinal metabolic enzymes-efflux transporters coupling will lay a foundation for improving the bioavailability of flavonoids <i>in vivo</i> and increasing their clinical efficacy.

scholarly journals Expression Analyses of Genes Related to Multixenobiotic Resistance in Mytilus galloprovincialis after Exposure to Okadaic Acid-Producing Dinophysis acuminate

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 614
Author(s):  
Roi Martínez-Escauriaza ◽  
Vanessa Lozano ◽  
M. Luz Pérez-Parallé ◽  
Juan Blanco ◽  
José L. Sánchez ◽  
...  
Keyword(s):  
Digestive Gland ◽  
Okadaic Acid ◽  
Mytilus Galloprovincialis ◽  
Aquatic Organisms ◽  
Resistance Mechanisms ◽  
Multixenobiotic Resistance ◽  
Main Production ◽  
Detoxification Process ◽  
Mdr Genes

The mussel Mytilus galloprovincialis is one of the most important aquaculture species in Europe. Its main production problem is the accumulation of toxins during coastal blooms, which prevents mussel commercialization. P-glycoprotein (ABCB1/MDR1/P-gp) is part of the multixenobiotic resistance system in aquatic organisms, and okadaic acid, the main DSP toxin, is probably a substrate of the P-gp-mediated efflux. In this study, the presence and possible role of P-gp in the okadaic acid detoxification process was studied in M. galloprovincialis. We identified, cloned, and characterized two complete cDNAs of mdr1 and mdr2 genes. MgMDR1 and MgMDR2 predicted proteins had the structure organization of ABCB full transporters, and were identified as P-gp/MDR/ABCB proteins. Furthermore, the expression of mdr genes was monitored in gills, digestive gland, and mantle during a cycle of accumulation-elimination of okadaic acid. Mdr1 significantly increased its expression in the digestive gland and gills, supporting the idea of an important role of the MDR1 protein in okadaic acid efflux out of cells in these tissues. The expression of M. galloprovincialismrp2, a multidrug associated protein (MRP/ABCC), was also monitored. As in the case of mdr1, there was a significant induction in the expression of mrp2 in the digestive gland, as the content of okadaic acid increased. Thus, P-gp and MRP might constitute a functional defense network against xenobiotics, and might be involved in the resistance mechanisms to DSP toxins.

scholarly journals The controversial role of ABC transporters in clinical oncology

2011 ◽  
Vol 50 ◽  
pp. 209-232 ◽  
Author(s):  
Akina Tamaki ◽  
Caterina Ierano ◽  
Gergely Szakacs ◽  
Robert W. Robey ◽  
Susan E. Bates
Keyword(s):  
Multidrug Resistance ◽  
Abc Transporters ◽  
Clinical Intervention ◽  
Cancer Resistance ◽  
P Glycoprotein ◽  
Cancer Types ◽  
Resistance Protein ◽  
Chemotherapy Efficacy ◽  
Transporter Expression

The phenomenon of multidrug resistance in cancer is often associated with the overexpression of the ABC (ATP-binding cassette) transporters Pgp (P-glycoprotein) (ABCB1), MRP1 (multidrug resistance-associated protein 1) (ABCC1) and ABCG2 [BCRP (breast cancer resistance protein)]. Since the discovery of Pgp over 35 years ago, studies have convincingly linked ABC transporter expression to poor outcome in several cancer types, leading to the development of transporter inhibitors. Three generations of inhibitors later, we are still no closer to validating the ‘Pgp hypothesis’, the idea that increased chemotherapy efficacy can be achieved by inhibition of transporter-mediated efflux. In this chapter, we highlight the difficulties and past failures encountered in the development of clinical inhibitors of ABC transporters. We discuss the challenges that remain in our effort to exploit decades of work on ABC transporters in oncology. In learning from past mistakes, it is hoped that ABC transporters can be developed as targets for clinical intervention.

scholarly journals Tissue-scale microbiota of the Mediterranean mussel (Mytilus galloprovincialis) and its relationship with the environment

2020 ◽  
Vol 717 ◽  
pp. 137209 ◽  
Author(s):  
Margherita Musella ◽  
Rasika Wathsala ◽  
Teresa Tavella ◽  
Simone Rampelli ◽  
Monica Barone ◽  
...  
Keyword(s):  
Mytilus Galloprovincialis ◽  
Mediterranean Mussel ◽  
The Mediterranean
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