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The pH-sensing receptor OGR1 improves barrier function of CaCo-2 cells and inhibits migration in an acidic environment

ABSTRACT: OGR1 is a pH-sensing G-protein coupled receptor involved in intestinal homeostasis and inflammation Proton activation of OGR1 increases barrier function in Caco2 cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE60294 | GEO | 2015/08/13

SECONDARY ACCESSION(S): PRJNA257969

REPOSITORIES: GEO

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The pH-sensing receptor OGR1 improves barrier function of CaCo-2 cells and inhibits migration in an acidic environment

Project description:OGR1 is a pH-sensing G-protein coupled receptor involved in intestinal homeostasis and inflammation Proton activation of OGR1 increases barrier function in Caco2 cells Microarray profiling was performed on OGR1 stable overexpressing Caco-2 cells during acidic pH shift

2015-08-13 | E-GEOD-60294 | biostudies-arrayexpress

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-02 | GSE213441 | GEO

Acidic pH sensing in the bacterial cytoplasm is required for Salmonella virulence.

Project description:pH regulates gene expression, biochemical activities and cellular behaviors. A mildly acidic pH activates the master virulence regulatory system PhoP/PhoQ in the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. The sensor PhoQ harbors an extracytoplasmic domain implicated in signal sensing, and a cytoplasmic domain controlling activation of the regulator PhoP. We now report that, surprisingly, a decrease in Salmonella's own cytoplasmic pH induces transcription of PhoP-activated genes even when the extracytoplasmic pH remains neutral. Amino acid substitutions in PhoQ's cytoplasmic domain hindered activation by acidic pH and attenuated virulence in mice, but did not abolish activation by low Mg(2+) or the antimicrobial peptide C18G. Conversely, removal of PhoQ's extracytoplasmic domains prevented the response to the latter PhoQ-activating signals but not to acidic pH. PhoP-dependent genes were minimally induced by acidic pH in the non-pathogenic species Salmonella bongori but were activated by low Mg(2+) and C18G as in pathogenic S. enterica. Our findings indicate that the sensor PhoQ enables S. enterica to respond to both host- and bacterial-derived signals that alter its cytoplasmic pH.

| S-EPMC5015592 | biostudies-literature

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein (scRNA-Seq)

Project description:Cytokines interact with their receptors in the extracellular space to control immune responses. How the physicochemical properties of the extracellular space influence cytokine signaling is incompletely elucidated. Here, we show that the activity of interleukin (IL)-2, a critical cytokine in T cell immunity, is profoundly affected by pH, limiting IL-2 signaling within the acidic environment of tumors. Generation of lactic acid by tumors limits STAT5 activation, effector differentiation and anti-tumor immunity by CD8+ T cells and renders high-dose IL-2 therapy poorly effective. Directed evolution enabled selection of a pH-selective IL-2 mutein (Switch-2). Switch-2 binds the IL-2 receptor subunit IL-2Ra with higher affinity, triggers STAT5 activation and drives CD8+ T cell effector function more potently at acidic pH than at neutral pH. Consequently, high-dose Switch-2 therapy induces potent immune activation and tumor rejection with reduced on-target toxicity in normal tissues. Finally, we find that sensitivity to pH is a generalizable property of a diverse range of cytokines with broad relevance to immunity and immunotherapy in healthy and diseased tissues.

2022-12-02 | GSE213440 | GEO

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein (RNA-Seq)

2022-12-02 | GSE213439 | GEO

PRO-cap from Caco-2 (ENCSR100LIJ)

Project description:A run-on assay that precisely maps the transcription start sites genome-wide with high sensitivity and specificity in CACO2. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf

2022-12-04 | GSE219461 | GEO

Acidic pH and divalent cation sensing by PhoQ are dispensable for systemic salmonellae virulence.

Project description:Salmonella PhoQ is a histidine kinase with a periplasmic sensor domain (PD) that promotes virulence by detecting the macrophage phagosome. PhoQ activity is repressed by divalent cations and induced in environments of acidic pH, limited divalent cations, and cationic antimicrobial peptides (CAMP). Previously, it was unclear which signals are sensed by salmonellae to promote PhoQ-mediated virulence. We defined conformational changes produced in the PhoQ PD on exposure to acidic pH that indicate structural flexibility is induced in ?-helices 4 and 5, suggesting this region contributes to pH sensing. Therefore, we engineered a disulfide bond between W104C and A128C in the PhoQ PD that restrains conformational flexibility in ?-helices 4 and 5. PhoQ(W104C-A128C) is responsive to CAMP, but is inhibited for activation by acidic pH and divalent cation limitation. phoQ(W104C-A128C) Salmonella enterica Typhimurium is virulent in mice, indicating that acidic pH and divalent cation sensing by PhoQ are dispensable for virulence.

| S-EPMC4473727 | biostudies-literature

Microalgal photoautotrophic growth induces pH decrease in the aquatic environment by acidic metabolites secretion.

Project description:BackgroundMicroalgae can absorb CO2 during photosynthesis, which causes the aquatic environmental pH to rise. However, the pH is reduced when microalga Euglena gracilis (EG) is cultivated under photoautotrophic conditions. The mechanism behind this unique phenomenon is not yet elucidated.ResultsThe present study evaluated the growth of EG, compared to Chlorella vulgaris (CV), as the control group; analyzed the dissolved organic matter (DOM) in the aquatic environment; finally revealed the mechanism of the decrease in the aquatic environmental pH via comparative metabolomics analysis. Although the CV cell density was 28.3-fold that of EG, the secreted-DOM content from EG cell was 49.8-fold that of CV (p-value < 0.001). The main component of EG's DOM was rich in humic acids, which contained more DOM composed of chemical bonds such as N-H, O-H, C-H, C=O, C-O-C, and C-OH than that of CV. Essentially, the 24 candidate biomarkers metabolites secreted by EG into the aquatic environment were acidic substances, mainly lipids and lipid-like molecules, organoheterocyclic compounds, organic acids, and derivatives. Moreover, six potential critical secreted-metabolic pathways were identified.ConclusionsThis study demonstrated that EG secreted acidic metabolites, resulting in decreased aquatic environmental pH. This study provides novel insights into a new understanding of the ecological niche of EG and the rule of pH change in the microalgae aquatic environment.

| S-EPMC9608927 | biostudies-literature

β-Barrel Nanopores with an Acidic-Aromatic Sensing Region Identify Proteinogenic Peptides at Low pH.

Project description:Biological nanopores are emerging as sensitive single-molecule sensors for proteins and peptides. The heterogeneous charge of a polypeptide chain, however, can complicate or prevent the capture and translocation of peptides and unfolded proteins across nanopores. Here, we show that two β-barrel nanopores, aerolysin and cytotoxin K, cannot efficiently detect proteinogenic peptides from a trypsinated protein under a wide range of conditions. However, the introduction of an acidic-aromatic sensing region in the β-barrel dramatically increased the dwell time and the discrimination of peptides in the nanopore at acidic pH. Surprisingly, despite the fact that the two β-barrel nanopores have a similar diameter and an acidic-aromatic construction, their capture mechanisms differ. The electro-osmotic flow played a dominant role for aerolysin, while the electrophoretic force dominated for cytotoxin K. Nonetheless, both β-barrel nanopores allowed the detection of mixtures of trypsinated peptides, with aerolysin nanopores showing a better resolution for larger peptides and cytotoxin K showing a better resolution for shorter peptides. Therefore, this work provides a generic strategy for modifying nanopores for peptide detection that will be most likely be applicable to other nanopore-forming toxins.

| S-EPMC9134492 | biostudies-literature

Proteomics of campylobacter exposed to host Caco-2 and INT407 intestinal cells

Project description:Comparison of Campylobacter proteome in MH media with and without deoxycholic acid, in presence of FBS or after being exposed to INT 407 and Caco2 intestinal epithelial cells.

2019-05-03 | PXD009817 | Pride

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