Nfat5 is involved in the hyperosmotic regulation of Tmem184b, which could be involved in ibuprofen transport in renal MDCK I cells
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ABSTRACT:
PROVIDER: PRJNA503406 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8145400_1.fastq.gz | Fastqsanger.gz | |||
| SRR8145400_2.fastq.gz | Fastqsanger.gz | |||
| SRR8145393_1.fastq.gz | Fastqsanger.gz | |||
| SRR8145393_2.fastq.gz | Fastqsanger.gz | |||
| SRR8145394_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: To investigate the involvement of Nfat5 in the regulation of an ibuprofen transporter Method: Reverse transfection with siRNA against Nfat5 was used to knockdown Nfat5 in MDCK I cells. The uptake of both radiolabelled taurine and ibuprofen was measured in MDCK I cells, first treated with siRNA against Nfat5 for 24 h and afterwards cultivated with raffinose-supplemented normal growth medium (500 mOsm) for 24 h. The knock down of NFat5 was investigated by qpCR and western blotting. A transcriptome analysis of MDCK I cells treated with siRNA against Nfat5 was performed. Validation of the transcriptome analysis was perform with qPCR and radiolabelled uptake of ibuprofen. Results: The siRNA transfection resulted in a knock down of Nfat5, and the uptake of both taurine and ibuprofen was significant decreased in the transfected MDCK I cells. The transcriptome analysis of MDCK I cells treated with siRNA against Nfat5 revealed genes regulated by Nfat5 during hyperosmotic exposure. qPCR and the transciptome analysis showed an involvement of Nfat5 in the hyperosmotic regulation of Tmem184 and uptake in Tmem184b-siRNA treated MDCK I cells showed that Tmem184b might be involved in uptake of ibuprofen. Conclusion: The regulation of Tmem184b was found regulated by Nfat5 and could be a potential possible candidate for the gene product responsible for the uptake of ibuprofen in MDCK I cells
2019-05-10 | GSE122074 | GEO
Project description:Nuclear factor of activated T cells 5 (NFAT5) is a transcription factor involved in the regulation of several genes involved in the response to extracellular hyperosmolality. Recently, the uptake of ibuprofen by an as yet unknown carrier was suggested in Madin-Darby canine kidney (MDCK) I cells exposed to hyperosmolality. We therefore speculated that Nfat5 could be involved in the regulation of this ibuprofen carrier. Reverse transfection with siRNA against Nfat5 was used to knock down Nfat5 in MDCK I cells. The uptake of both radiolabelled taurine and ibuprofen was measured in MDCK I cells, first treated with siRNA against Nfat5 and afterwards cultivated with raffinose-supplemented normal growth medium (500 mOsm) for 24 h. The siRNA transfection resulted in knockdown of Nfat5, and uptake of both taurine and ibuprofen was significantly decreased in transfected MDCK I cells. The decrease in ibuprofen uptake indicates that Nfat5 is involved in upregulation of the ibuprofen carrier. A transcriptome analysis of MDCK I cells treated with siRNA against Nfat5 revealed 989 genes upregulated by Nfat5 during hyperosmotic exposure. From these genes, the gene product transmembrane protein 184b was found to be regulated by Nfat5, and Tmem184b was the only potential gene product involved in the uptake of ibuprofen in MDCK I cells. DATASET: The RNA sequencing dataset is available from the NCBI Gene Expression 452 Omnibus (https://www.ncbi.nlm.nih.gov/geo/) with the accession number GSE122074.
| S-EPMC6551498 | biostudies-literature
Project description:The goal of this study was to evaluate gene expression that is dependent upon Tmem184b expression. Our objective was to identify pathways controlled by Tmem184b that may influence development or behavior of neurons.
2020-07-14 | GSE154316 | GEO
Project description:Disruption of endolysosomal acidification is a hallmark of several neurodevelopmental and neurodegenerative disorders. Impaired acidification causes accumulation of toxic protein aggregates and disrupts neuronal homeostasis, yet the molecular mechanisms regulating endolysosomal pH in neurons remain poorly understood. A critical regulator of lumenal acidification is the vacuolar ATPase (VATPase), a proton pump whose activity depends on dynamic assembly of its V0 and V1 subdomains. In this study, we identify transmembrane protein 184B (TMEM184B) as a novel regulator of endolysosomal acidification in neurons. TMEM184B is an evolutionarily conserved 7-pass transmembrane protein required for synaptic structure and function, and sequence variation in TMEM184B causes neurodevelopmental disorders, but the mechanism for this effect is unknown. We performed proteomic analysis of TMEM184B-interacting proteins and identified enrichment of components involved in endosomal trafficking and function, including the V-ATPase. TMEM184B localizes to early and late endosomes, further supporting a role in the endosomal system. Loss of TMEM184B results in significant reductions in endolysosomal acidification within cultured mouse cortical neurons. This alteration in pH is associated with impaired assembly of the V-ATPase V0 and V1 subcomplexes in the TMEM184B mutant mouse brain, suggesting a mechanism by which TMEM184B promotes flux through the endosomal pathway. Overall, these findings identify a new contributor in maintaining endosomal function and provide a mechanistic basis for disrupted neuronal function in human TMEM184B-associated nervous system disorders.
2025-06-16 | PXD064977 | Pride
Project description:We evaluated transcriptomic signatures at critical timepoints of sensory differentiation in wild type and Tmem184b mutant mice.
2020-07-14 | GSE154354 | GEO
Project description:Ibuprofen is one of the most commonly detected pharmaceuticals in wastewater effluent; however the effects of ibuprofen on aquatic organisms are poorly understood. This study presents the transcriptome-wide response of the inland silverside, Menidia beryllina, to chronic 14 d exposures to ibuprofen.
2015-09-01 | GSE64967 | GEO
Project description:Transcriptional profiling of small intestinal explants cultured in the absence or in the presence of Ibuprofen (100 µM). Two-condition experiment, control intestinal explants vs Ibuprofen intestinal explants
2019-01-07 | GSE108369 | GEO
Project description:Ibuprofen is one of the most commonly detected pharmaceuticals in wastewater effluent; however the effects of ibuprofen on aquatic organisms are poorly understood. This study presents the transcriptome-wide response of the inland silverside, Menidia beryllina, to chronic 14 d exposures to ibuprofen. Twenty-four samples were run on twenty-four arrays, there were six replicates for each of three ibuprofen exposure concentrations and a control group.
2015-09-01 | E-GEOD-64967 | biostudies-arrayexpress
Project description:Several pharmaceuticals persist in wastewater plants and contaminate increasingly natural water bodies, even ground water. In this study, different bacteria with known capabilities to degrade aromatic environmental pollutants – belonging to the genera Bacillus, Paenibacillus, Mycobacterium and Cupriavidus - were screened for their ability to transform the anti-inflammatory drug ibuprofen. Bacillus megaterium SBUG 518 as one of the most efficient strains tested was almost completely inhibited by 0.05% ibuprofen at pH 6 but was able to transform 0.005% ibuprofen within 4 h up to 92%. Four products were identified by HPLC and LC/MS. The drug was transformed via three different biotransformation reactions involving (A) conjugate formation of ibuprofen with a sugar molecule (B) the hydroxylation of the isobutyl side chain at two positions, and (C) glycosylation of 2-hydroxyibuprofen. The ibuprofen conjugate (ibuprofen pyranoside) was considerably less toxic to B. megaterium than the parent compound. Its reversible formation can lead to a temporary remarkable underestimation of ibuprofen concentrations in environmental “elimination” studies. Proteomic analyses including 1264 identified proteins suggest that cytochrome P450 BM3 plays a pivotal role in ibuprofen hydroxylation. Additionally, several proteins involved in stress response as well as proteins with similarity to multidrug efflux pump proteins were found in higher abundance in ibuprofen-incubated bacteria.
2025-04-14 | PXD015716 | Pride
Project description:Oral streptococci metabolize carbohydrate to produce organic acids, not only decrease the environmental pH, but also increase osmolality of dental plaque fluid due to tooth demineralization and consequent calcium and phosphate accumulation. Thus, to persevere in the dental plaque, acidogenic bacteria should evolve sophisticated molecular machineries to counter the detrimental effect of elevated osmolality. This study was aimed to obtain a global view on strategies taken by streptococcus mutans to deal with physiologically relevant elevated osmolality, and preserves within a cariogenic dental plaque. We investigated phenotypic change of S. mutans biofilm upon sub-lethal level of hyperosmotic challenge. We found that hyperosmotic condition was able to initiate S. mutans biofilm dispersal by reducing both microbial content and extracellular polysaccharides matrix. We then used DNA microarray with qPCR validation to systemically investigate the underlying molecular machinery of this bacteria in response to hyperosmotic stimuli. Among those identified 50 differentially regulated genes, down-regulation of gtfB and comC were believed to be responsible for the observed biofilm dispersal. Further analysis of microarray data showed significant up-regulation of genes and pathways involved in carbohydrates metabolism. Specific genes involved in heat shock response and acid tolerance were also upregulated, indicating potential cross-talk between hyperosmotic and other environmental stress. Based on the data obtained in this study, we believe that although hyperosmotic condition may induce significant stress response on S. mutans, this cariogenic bacterium has evolved sophisticated molecular machineries to counter those elicited detrimental effects. In the meantime, it will take full advantage of these environmental stimuli to better fit the fluctuating environments within oral cavity, and thus emerge as numeric-predominant bacteria under cariogenic conditions. A six-chip study using total RNA recovered from mid-logarithmic phase of S. mutans UA159 from three separate cultures of strains submitted for 15 minutes to hyperosmotic stimuli (0.4M NaCl) and three separate cultures of strains kept under no stress condition.
2013-08-31 | E-GEOD-47170 | biostudies-arrayexpress