scholarly journals Stickleback embryos use ATP-binding cassette transporters as a buffer against exposure to maternally derived cortisol

2016 ◽  
Vol 283 (1826) ◽  
pp. 20152838 ◽  
Author(s):  
Ryan T. Paitz ◽  
Syed Abbas Bukhari ◽  
Alison M. Bell

Offspring from females that experience stressful conditions during reproduction often exhibit altered phenotypes and many of these effects are thought to arise owing to increased exposure to maternal glucocorticoids. While embryos of placental vertebrates are known to regulate exposure to maternal glucocorticoids via placental steroid metabolism, much less is known about how and whether egg-laying vertebrates can control their steroid environment during embryonic development. We tested the hypothesis that threespine stickleback ( Gasterosteus aculeatus ) embryos can regulate exposure to maternal steroids via active efflux of maternal steroids from the egg. Embryos rapidly (within 72 h) cleared intact steroids, but blocking ATP-binding cassette (ABC) transporters inhibited cortisol clearance. Remarkably, this efflux of cortisol was sufficient to prevent a transcriptional response of embryos to exogenous cortisol. Taken together, these findings suggest that, much like their placental counterparts, developing fish embryos can actively regulate their exposure to maternal cortisol. These findings highlight the fact that even in egg-laying vertebrates, the realized exposure to maternal steroids is mediated by both maternal and embryonic processes and this has important implications for understanding how maternal stress influences offspring development.

2017 ◽  
Vol 9 (4) ◽  
Author(s):  
Antonella Maria Salvia ◽  
Flavia Cuviello ◽  
Sabrina Coluzzi ◽  
Roberta Nuccorini ◽  
Immacolata Attolico ◽  
...  

Hematopoietic cells express ATP binding cassette (ABC) transporters in relation to different degrees of differentiation. One of the known multidrug resistance mechanisms in acute myeloid leukemia (AML) is the overexpression of efflux pumps belonging to the superfamily of ABC transporters such as ABCB1, ABCG2 and ABCC1. Although several studies were carried out to correlate ABC transporters expression with drug resistance, little is known about their role as markers of diagnosis and progression of the disease. For this purpose we investigated the expression, by real-time PCR, of some ABC genes in bone marrow samples of AML patients at diagnosis and after induction therapy. At diagnosis, ABCG2 was always down-regulated, while an up regulated trend for ABCC1 was observed. After therapy the examined genes showed a different expression trend and approached the values of healthy subjects suggesting that this event could be considered as a marker of AML regression. The expression levels of some ABC transporters such as ABCC6, seems to be related to gender, age and to the presence of FLT3/ITD gene mutation.


2014 ◽  
Vol 27 (7) ◽  
pp. 725-732 ◽  
Author(s):  
Mukesh K. Dubey ◽  
Dan Funck Jensen ◽  
Magnus Karlsson

ATP-binding cassette (ABC) transporters mediate active efflux of natural and synthetic toxicants and are considered to be important for drug tolerance in microorganisms. In biological control agents (BCA), ABC transporters can play important roles in antagonism by providing protection against toxins derived from the fungal prey and by mediating the secretion of endogenous toxins. In the present study, we generated deletion and complementation strains of the ABC transporter abcG5 in the fungal BCA Clonostachys rosea to study its role in xenobiotic tolerance and antagonism. Gene expression analysis shows induced expression of abcG5 in the presence of the Fusarium mycotoxin zearalenone (ZEA), secreted metabolites of F. graminearum, and different classes of fungicides. Phenotypic analysis of abcG5 deletion and complementation strains showed that the deletion strains were more sensitive towards F. graminearum culture filtrates, ZEA, and iprodione- and mefenoxam-based fungicides, thus suggesting the involvement of abcG5 in cell protection. The ΔabcG5 strains displayed reduced antagonism towards F. graminearum in a plate confrontation assay. Furthermore, the ΔabcG5 strains failed to protect barley seedlings from F. graminearium foot rot disease. These data show that the abcG5 ABC transporter is important for xenobiotic tolerance and biocontrol traits in C. rosea.


2019 ◽  
Author(s):  
Folukemi Adedipe ◽  
Nathaniel Grubbs ◽  
Brad Coates ◽  
Brian Wiegmman ◽  
Marce Lorenzen

Abstract Background The western corn rootworm, Diabrotica virgifera virgifera , is a pervasive pest of cultivated maize in North America and Europe, which has adapted to survive exposure to multiple insecticidal agents. Due to their role in insecticide transport, we sought to identify members of the ATP-binding cassette (ABC) transporter family in D. v. virgifera using a transcriptomics approach.Results In this study, 65 putative D. v. virgifera ABC ( Dvv ABC) transporters were identified within a combined transcriptome assembly generated from embryonic, larval, adult male, and adult female RNA-sequence libraries. Phylogenetic analysis placed the deduced amino-acid sequences of the Dvv ABC transporters into eight subfamilies (A to H). Of these, eight shared structural and functional conservation with Tribolium castaneum ABC transporter orthologs known to exhibit overt RNA interference (RNAi) knockdown phenotypes. Interestingly, depletion of DvvABCB_19147 and DvvABCG_3712 transcripts in adult females produced detrimental reproductive and developmental phenotypes (egg-laying or -hatching defects), demonstrating the potential of these genes as targets for RNAi-mediated insect control tactics.Conclusions By combining sequence data from four libraries covering three distinct life stages, we have produced a relatively comprehensive de novo transcriptome assembly for D. v. virgifera . Moreover, we have identified 65 members of the ABC transporter family, and provided the first insights into the developmental and physiological roles of ABC transporters in this pest species.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charbel Al Khoury ◽  
Nabil Nemer ◽  
Georges Nemer

AbstractMulti-drug resistance is posing major challenges in suppressing the population of pests. Many herbivores develop resistance, causing a prolonged survival after exposure to a previously effective pesticide. Consequently, resistant pests reduce the yield of agricultural production, causing significant economic losses and reducing food security. Therefore, overpowering resistance acquisition of crop pests is a must. The ATP binding cassette transporters (ABC transporters) are considered as the main participants to the pesticide efflux and their neutralization will greatly contribute to potentiate failed treatments. Real-Time PCR analysis of 19 ABC transporter genes belonging to the ABCB, ABCC, ABCG, and ABCH revealed that a broad range of efflux pumps is activated in response to the exposure to pesticides. In this study, we used beauvericin (BEA), a known ABC transporters modulator, to resensitize different strains of Tetranychus urticae after artificial selection for resistance to cyflumetofen, bifenazate, and abamectin. Our results showed that the combinatorial treatment of pesticide (manufacturer’s recommended doses) + BEA (sublethal doses: 0.15 mg/L) significantly suppressed the resistant populations of T. urticae when compared to single-drug treatments. Moreover, after selective pressure for 40 generations, the LC50 values were significantly reduced from 36.5, 44.7, and 94.5 (pesticide) to 8.3, 12.5, and 23.4 (pesticide + BEA) for cyflumetofen, bifenazate, and abamectin, respectively. While the downstream targets for BEA are still elusive, we demonstrated hereby that it synergizes with sub-lethal doses of different pesticides and increases their effect by inhibiting ABC transporters. This is the first report to document such combinatorial activity of BEA against higher invertebrates paving the way for its usage in treating refractory cases of resistance to pesticides. Moreover, we demonstrated, for the first time, using in silico techniques, the higher affinity of BEA to ABC transformers subfamilies when compared to xenobiotics; thus, elucidating the pathway of the mycotoxin.


2021 ◽  
Author(s):  
Parul Sharma ◽  
Navneet Singh ◽  
Siddharth Sharma

The expression of ATP-binding cassette transporter (ABC transporters) has been reported in various tissues such as the lung, liver, kidney, brain and intestine. These proteins account for the efflux of different compounds and metabolites across the membrane, thus decreasing the concentration of the toxic compounds. ABC transporter genes play a vital role in the development of multidrug resistance, which is the main obstacle that hinders the success of chemotherapy. Preclinical and clinical trials have investigated the probability of overcoming drug-associated resistance and substantial toxicities. The focus has been put on several strategies to overcome multidrug resistance. These strategies include the development of modulators that can modulate ABC transporters. This knowledge can be translated for clinical oncology treatment in the future.


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