scholarly journals Expression and phylogeny of multidrug resistance protein 2 and 4 in African white backed vulture (Gyps africanus)

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10422
Author(s):  
Bono Nethathe ◽  
Aron Abera ◽  
Vinny Naidoo

Diclofenac toxicity in old world vultures is well described in the literature by both the severity of the toxicity induced and the speed of death. While the mechanism of toxicity remains unknown at present, the necropsy signs of gout suggests primary renal involvement at the level of the uric acid excretory pathways. From information in the chicken and man, uric acid excretion is known to be a complex process that involves a combination of glomerular filtration and active tubular excretion. For the proximal convoluted tubules excretion occurs as a two-step process with the basolateral cell membrane using the organic anion transporters and the apical membrane using the multidrug resistant protein to transport uric acid from the blood into the tubular fluid. With uric acid excretion seemingly inhibited by diclofenac, it becomes important to characterize these transporter mechanism at the species level. With no information being available on the molecular characterization/expression of MRPs of Gyps africanus, for this study we used next generation sequencing, and Sanger sequencing on the renal tissue of African white backed vulture (AWB), as the first step to establish if the MRPs gene are expressed in AWB. In silico analysis was conducted using different software to ascertain the function of the latter genes. The sequencing results revealed that the MRP2 and MRP4 are expressed in AWB vultures. Phylogeny of avian MRPs genes confirms that vultures and eagles are closely related, which could be attributed to having the same ancestral genes and foraging behavior. In silico analysis confirmed the transcribed proteins would transports anionic compounds and glucose.

2008 ◽  
Vol 295 (3) ◽  
pp. C761-C767 ◽  
Author(s):  
William Silverman ◽  
Silviu Locovei ◽  
Gerhard Dahl

Probenecid is a well-established drug for the treatment of gout and is thought to act on an organic anion transporter, thereby affecting uric acid excretion in the kidney by blocking urate reuptake. Probenecid also has been shown to affect ATP release, leading to the suggestion that ATP release involves an organic anion transporter. Other pharmacological evidence and the observation of dye uptake, however, suggest that the nonvesicular release of ATP is mediated by large membrane channels, with pannexin 1 being a prominent candidate. In the present study we show that probenecid inhibited currents mediated by pannexin 1 channels in the same concentration range as observed for inhibition of transport processes. Probenecid did not affect channels formed by connexins. Thus probenecid allows for discrimination between channels formed by connexins and pannexins.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jing Pan ◽  
Liang Ma ◽  
Ping Fu

Abstract Background and Aims The barks of Liriodendron Chinense (Hemsl.) Sarg is used in folk for expelling “wind and dampness”, alleviating rheumatic arthralgia in traditional Chinese medicine. The aim of the study was to evaluate the protective effect of ethanol extract of the barks of Liriodendron Chinense (Hemsl.) Sarg (EELC) in a mouse model of hyperuricemic nephropathy (HN) and the mechanisms involved. Method EELC at a respective dose of 250 mg/kg/d or 500 mg/kg/d were orally administered to HN mice induced by a mixture of adenine (160 mg/kg/d)/potassium oxonate (2.4 g/kg/d) for 21 days. At the end of the treatment, serum uric acid, kidney functions (serum creatinine, BUN and urine microalbumin), 24-h urine uric acid excretion, as well as kidney pathological changes were investigated by biochemical assay, histopathological score, immunofluorescence and histochemistry, RT-PCR, and western blotting analysis. Results Oral administration of EELC to HN mice lowered serum uric acid, improved renal functions and attenuated renal fibrosis, especially the high-dose of EELC. EELC treatment also inhibited the activation of NF-κB, ASK1/JNK/c-Jun, JAK2/STAT3 signaling pathways and reduced the release of pro-inflammatory cytokine TNF-α in the kidneys of HN mice. Furthermore, EELC remarkably increased urine uric acid excretion of HN mice, which may be achieved by the upregulation of organic anion transporter 1 (OAT1), OAT3 and ATP-binding cassette subfamily G member 2 (ABCG2) proteins. Conclusion EELC alleviated the progression of HN by suppressing the activation of NF-κB, ASK1/JNK/c-Jun and JAK2/STAT3 signaling pathway, reducing the infiltration of inflammatory factors and uric acid accumulation in the kidney. Figure Date are represented as the mean ± SD. *p<0.05,**p<0.01,***p<0.001, ****p<0.0001 vs. control, §p <0.05, §§p<0.01, §§§p<0.001,§§§§p<0.0001 vs. model.


2020 ◽  
Vol 47 (6) ◽  
pp. 398-408
Author(s):  
Sonam Tulsyan ◽  
Showket Hussain ◽  
Balraj Mittal ◽  
Sundeep Singh Saluja ◽  
Pranay Tanwar ◽  
...  

2020 ◽  
Vol 27 (38) ◽  
pp. 6523-6535 ◽  
Author(s):  
Antreas Afantitis ◽  
Andreas Tsoumanis ◽  
Georgia Melagraki

Drug discovery as well as (nano)material design projects demand the in silico analysis of large datasets of compounds with their corresponding properties/activities, as well as the retrieval and virtual screening of more structures in an effort to identify new potent hits. This is a demanding procedure for which various tools must be combined with different input and output formats. To automate the data analysis required we have developed the necessary tools to facilitate a variety of important tasks to construct workflows that will simplify the handling, processing and modeling of cheminformatics data and will provide time and cost efficient solutions, reproducible and easier to maintain. We therefore develop and present a toolbox of >25 processing modules, Enalos+ nodes, that provide very useful operations within KNIME platform for users interested in the nanoinformatics and cheminformatics analysis of chemical and biological data. With a user-friendly interface, Enalos+ Nodes provide a broad range of important functionalities including data mining and retrieval from large available databases and tools for robust and predictive model development and validation. Enalos+ Nodes are available through KNIME as add-ins and offer valuable tools for extracting useful information and analyzing experimental and virtual screening results in a chem- or nano- informatics framework. On top of that, in an effort to: (i) allow big data analysis through Enalos+ KNIME nodes, (ii) accelerate time demanding computations performed within Enalos+ KNIME nodes and (iii) propose new time and cost efficient nodes integrated within Enalos+ toolbox we have investigated and verified the advantage of GPU calculations within the Enalos+ nodes. Demonstration data sets, tutorial and educational videos allow the user to easily apprehend the functions of the nodes that can be applied for in silico analysis of data.


2013 ◽  
Vol 9 (4) ◽  
pp. 608-616 ◽  
Author(s):  
Zaheer Ul-Haq ◽  
Saman Usmani ◽  
Uzma Mahmood ◽  
Mariya al-Rashida ◽  
Ghulam Abbas

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