ph regulation
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2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Vladimir Riazanski ◽  
Gerardo Mauleon ◽  
Kilean Lucas ◽  
Samuel Walker ◽  
Adriana M. Zimnicka ◽  
...  

AbstractExtracellular vesicles (EVs) are cell-derived membranous structures carrying transmembrane proteins and luminal cargo. Their complex cargo requires pH stability in EVs while traversing diverse body fluids. We used a filtration-based platform to capture and stabilize EVs based on their size and studied their pH regulation at the single EV level. Dead-end filtration facilitated EV capture in the pores of an ultrathin (100 nm thick) and nanoporous silicon nitride (NPN) membrane within a custom microfluidic device. Immobilized EVs were rapidly exposed to test solution changes driven across the backside of the membrane using tangential flow without exposing the EVs to fluid shear forces. The epithelial sodium-hydrogen exchanger, NHE1, is a ubiquitous plasma membrane protein tasked with the maintenance of cytoplasmic pH at neutrality. We show that NHE1 identified on the membrane of EVs is functional in the maintenance of pH neutrality within single vesicles. This is the first mechanistic description of EV function on the single vesicle level.


Der Hautarzt ◽  
2022 ◽  
Author(s):  
Ferdinand Toberer ◽  
Julia K. Winkler ◽  
Holger A. Haenssle ◽  
Monika Heinzel-Gutenbrunner ◽  
Alexander Enk ◽  
...  

ZusammenfassungMetabolische Anpassungsprozesse, vermittelt durch sog. Hypoxie-induzierbare Faktoren und deren Zielgene, spielen in zahlreichen Malignomen eine wichtige Rolle. Rasch wachsende Tumoren können ihre Stoffwechselvorgänge an eine auftretende Hypoxie anpassen. So werden beispielsweise nach der Aktivierung des „Hypoxia inducible-factors-1α“ Modifikationen am Glukosestoffwechsel, der intrazellulären pH-Regulation oder der Angiogenese initiiert. In dieser immunhistochemischen Pilotstudie analysierten wir primär kutane Melanome mit positivem und negativem Schildwächterlymphknotenstatus im Hinblick auf mögliche Unterschiede ihrer metabolischen Signatur. Hierbei konnten wir unter anderem zeigen, dass die Expression von Glukosetransporter‑1 (GLUT-1) sowohl in allen Melanomen ohne Subgruppenanalyse, als auch in der Subgruppe mit negativem Schildwächterlymphknoten positiv mit der Tumordicke sowie dem Vorliegen einer Ulzeration korrelierte. Zudem korrelierte bei Melanomen mit positivem Schildwächterlymphknoten die Expression von vaskulärem endothelialem Wachstumsfaktor (VEGF) positiv mit dem Vorliegen einer Ulzeration.


eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Daniel Walter McKay ◽  
Heather E McFarlane ◽  
Yue Qu ◽  
Apriadi Situmorang ◽  
Matthew Gilliham ◽  
...  

Plant cells maintain a low luminal pH in the Trans-Golgi-Network/Early Endosome (TGN/EE), the organelle in which the secretory and endocytic pathways intersect. Impaired TGN/EE pH regulation translates into severe plant growth defects. The identity of the proton pump and proton/ion antiporters that regulate TGN/EE pH have been determined, but an essential component required to complete the TGN/EE membrane transport circuit remains unidentified - a pathway for cation and anion efflux. Here, we have used complementation, genetically encoded fluorescent sensors, and pharmacological treatments to demonstrate that Arabidopsis Cation Chloride Cotransporter (CCC1) is this missing component necessary for regulating TGN/EE pH and function. Loss of CCC1 function leads to alterations in TGN/EE-mediated processes including endocytic trafficking, exocytosis and response to abiotic stress, consistent with the multitude of phenotypic defects observed in ccc1 knockout plants. This discovery places CCC1 as a central component of plant cellular function.


Author(s):  
Zhenfeng Wang ◽  
Jiadi Lv ◽  
Pin Yu ◽  
Yajin Qu ◽  
Yabo Zhou ◽  
...  

AbstractExploring the cross-talk between the immune system and advanced biomaterials to treat SARS-CoV-2 infection is a promising strategy. Here, we show that ACE2-overexpressing A549 cell-derived microparticles (AO-MPs) are a potential therapeutic agent against SARS-CoV-2 infection. Intranasally administered AO-MPs dexterously navigate the anatomical and biological features of the lungs to enter the alveoli and are taken up by alveolar macrophages (AMs). Then, AO-MPs increase the endosomal pH but decrease the lysosomal pH in AMs, thus escorting bound SARS-CoV-2 from phago-endosomes to lysosomes for degradation. This pH regulation is attributable to oxidized cholesterol, which is enriched in AO-MPs and translocated to endosomal membranes, thus interfering with proton pumps and impairing endosomal acidification. In addition to promoting viral degradation, AO-MPs also inhibit the proinflammatory phenotype of AMs, leading to increased treatment efficacy in a SARS-CoV-2-infected mouse model without side effects. These findings highlight the potential use of AO-MPs to treat SARS-CoV-2-infected patients and showcase the feasibility of MP therapies for combatting emerging respiratory viruses in the future.


Lab on a Chip ◽  
2022 ◽  
Author(s):  
Logan M. Wilder ◽  
Jonathan R. Thompson ◽  
Richard M. Crooks

The pH of droplets moving through a microchannel is regulated in real time by water electrolysis. Resulting droplet pHs are within ±0.1 pH units of the predicted values.


2021 ◽  
Author(s):  
Dong-Joon Lee ◽  
Pyunggang Kim ◽  
Hyun-Yi Kim ◽  
Jinah Park ◽  
Seung-Jun Lee ◽  
...  

Asymmetric division of stem cells allows for maintenance of the cell population and differentiation for harmonious progress. Developing mouse incisors allows for examin ation of how the stem cell niche employs specific insights into essential phases. Microtubule associated serine/threonine kinase family member 4 (Mast4) knockout (KO) mice showed abnormal incisor development with weak hardness as the apical bud was reduced and preameloblasts were shifted to the apical side, resulting in Amelogenesis Imperfecta. In addition, Mast4) KO incisors showed abnormal enamel maturation, and stem cell maintenance was inhibited as amelogenesis accelerated. Distal-Less Homeobox 3 (DLX3), known to be a critical factor Tricho Dento Osseous (TDO) syndrome, is considered to be responsible for A melogenesis Imperfecta in humans. MAST4 directly binds to DLX3 and induces phosphorylation at three residues within the nuclear localization sites (NLS) that promote the nuclear translocation of DLX3. MAST4-mediated phosphorylation of DLX3 ultimately controls the transcription of DLX3 target genes, which are carbonic anhydrase and ion transporter genes involved in the pH regulation process during ameloblast maturation. Taken together, our data reveal a novel role of MAST4 as a critical regulator of ameloblast maturation, which controls DLX3 transcriptional activity.


Materials ◽  
2021 ◽  
Vol 14 (24) ◽  
pp. 7659
Author(s):  
Anna Y. Gyurova ◽  
Kaloyan Berberov ◽  
Alexander Chinarev ◽  
Ljubomir Nikolov ◽  
Daniela Karashanova ◽  
...  

Bacterial lipopolysaccharides (LPS) are designated as endotoxins, because they cause fever and a wide range of pathologies in humans. It is important to develop effective methodologies to detect trace quantities of LPS in aqueous systems. The present study develops a fine-tuning procedure for the entrapment of trace quantities of LPS from E. coli EH100. The capture agents are self-assemblies (tectomers) formed by synthetic four-antennary oligoglycine (C-(CH2-NH-Gly7)4, T4). Based on previously performed investigations of bulk and adsorption-layer properties of aqueous solutions containing T4 and LPS, the optimal conditions for the entrapment interactions are further fine-tuned by the pH regulation of aqueous systems. A combined investigation protocol is developed, including dynamic light scattering, profile analysis tensiometry, microscopic thin-liquid-film techniques, and transmission electron microscopy. The key results are: (1) two types of complexes between T4 and LPS are generated—amphiphilic species and “sandwich-like” hydrophilic entities; the complexes are smaller at lower pH, and larger at higher pH; (2) an optimum range of pH values is established within which the whole quantity of the LPS is entrapped by the tectomers, namely pH = 5.04–6.30. The obtained data substantiate the notion that T4 may be used for an effective capture and the removal of traces of endotoxins in aqueous systems.


2021 ◽  
Author(s):  
Garfield Tsz Kwan ◽  
Martin Tresguerres

Over a decade ago, ocean acidification (OA) exposure was reported to induce otolith overgrowth in teleost fish. This phenomenon was subsequently confirmed in multiple species; however, the underlying physiological causes remain unknown. Here, we report that splitnose rockfish (Sebastes diploproa) exposed to ~1,600 μatm pCO2 (pH ~7.5) were able to fully regulated the pH of both blood and endolymph (the fluid that surrounds the otolith within the inner ear). However, while blood was regulated around pH 7.80, the endolymph was regulated around pH ~8.30. These different pH setpoints result in increased pCO2 diffusion into the endolymph, which in turn leads to proportional increases in endolymph [HCO3-] and [CO32-]. Endolymph pH regulation despite the increased pCO2 suggests enhanced H+ removal. However, a lack of differences in inner ear bulk and cell-specific Na+/K+-ATPase and vacuolar type H+-ATPase protein abundance localization pointed out to activation of preexisting ATPases, non-bicarbonate pH buffering, or both, as the mechanism for endolymph pH-regulation. These results provide the first direct evidence showcasing the acid-base chemistry of the endolymph of OA-exposed fish favors otolith overgrowth, and suggests that this phenomenon will be more pronounced in species that count with more robust blood and endolymph pH regulatory mechanisms.


2021 ◽  
Author(s):  
Eva Kaulich ◽  
Brian D Ackley ◽  
Yi Quan Tang ◽  
Iris Hardege ◽  
William Schafer ◽  
...  

Biological clocks are fundamental to an organism′s health, controlling periodicity of behavior and metabolism. Here, we identify two acid-sensing ion channels, with very different proton sensing properties, and describe their role in an ultradian clock, the defecation motor program (DMP) of the nematode Caenorhabditis elegans. An ACD-5-containing channel, on the apical membrane of the intestinal epithelium, is essential for maintenance of luminal acidity, and thus the rhythmic oscillations in lumen pH. In contrast, the second channel, composed of FLR-1, ACD-3 and/or DEL-5, located on the basolateral membrane, controls the intracellular Ca2+ wave and forms a core component of the master oscillator that controls timing and rhythmicity of the DMP. flr-1 and acd-3/del-5 mutants show severe developmental and metabolic defects. We thus directly link the proton-sensing properties of these channels to their physiological roles in pH regulation and Ca2+ signaling, the generation of an ultradian oscillator, and its metabolic consequences.


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