TY - JOUR. T1 - The oxindole Syk inhibitor OXSI-2 blocks nigericin-induced inflammasome signaling and pyroptosis independent of potassium efflux. AU - Yaron, Jordan R.. AU - Rao, Mounica Y.. AU - Gangaraju, Sandhya. AU - Zhang, Liqiang. AU - Kong, Xiangxing. AU - Su, Fengyu. AU - Tian, Yanqing. AU - Glenn, Honor L.. AU - Meldrum, Deirdre. PY - 2016/2/11. Y1 - 2016/2/11. N2 - The inflammasome is a caspase-1-activating complex that is implicated in a growing number of acute and chronic pathologies. Interest has increased in identifying small molecular inhibitors of inflammasome signaling because of its role in clinically relevant diseases. It was recently reported that the protein tyrosine kinase, Syk, regulates pathogen-induced inflammasome signaling by phosphorylating a molecular switch on the adapter protein ASC. However, several aspects of the role of Syk in inflammasome signaling and the effects of its inhibition remain unclear. The aim of the present study is to explore in detail the effects ...
Strains with increased alkali tolerance have a broad application in industrial, especially for bioremediation, biodegradation, biocontrol and production of bio-based chemicals. A novel synthetic chromosome recombination and modification by LoxP-mediated evolution (SCRaMbLE) system has been introduced in the synthetic yeast genome (Sc 2.0), which enables generation of a yeast library with massive structural variations and potentially drives phenotypic evolution. The structural variations including deletion, inversion and duplication have been detected within synthetic yeast chromosomes. Haploid yeast strains harboring either one (synV) or two (synV and synX) synthetic chromosomes were subjected to SCRaMbLE. Seven of evolved strains with increased alkali tolerance at pH 8.0 were generated through multiple independent SCRaMbLE experiments. Various of structural variations were detected in evolved yeast strains by PCRTag analysis and whole genome sequencing including two complex structural variations. One
In pyroptosis experiments, nigericin can be used as a positive control to generate a robust caspase-1 activation response in a variety of cell lines.
Perturbation of intracellular ion homeostasis is a major cellular stress signal for activation of NLRP3 inflammasome signaling. However, the relative contributions of decreased cytosolic [K+] versus increased cytosolic [Ca2+] remain disputed and incompletely defined. This study provides three major findings relevant to this unresolved area of NLRP3 regulation. First, increased cytosolic [Ca2+] is neither a necessary nor sufficient signal for the NLRP3 inflammasome cascade induced in murine DC and macrophages during activation by endogenous ATP-gated P2X7 receptor channels, the bacterial ionophore nigericin, or LLME-induced lysosomal disruption. These stimuli are widely used as highly efficacious inducers of NLPR3 inflammasome assembly in murine and human myeloid leukocyte models. Second, agonists for three Ca2+-mobilizing GPCR expressed in murine myeloid leukocytes (FPR, P2Y2 purinergic receptor, CaSR) were ineffective as robust activators of NLRP3 signaling when directly compared with the K+ ...
Staphylococcus aureus is a commensal colonizer of 20 to 30% of healthy people as normal flora of the nasopharynx, skin, and other secondary niches (1). Colonization leads to elevated risk for metastatic S. aureus infections of the host. S. aureus strains cause a large diversity of infections (1, 2). Factors underpinning this diversity include robust stress resilience, biofilm formation, resistance to successive antibiotics, generation of antibiotic-tolerant persisters, and evasion of the host immune response (3-6). S. aureus not only is prevalent in hospital settings but also has survival efficiency in hostile environments. It successfully survives in high saline up to 25% NaCl, which is commonly found in canned foods. The low water activity (aw) makes the bacteria uniquely resistant to drying and capable of growing and producing enterotoxins in foods with low aw (7, 8). S. aureus lives in highly alkaline (pH up to 9.5) conditions that are found in garden soil, sewage, ground water, and some ...
This page contains information on the chemical Lonomycin A, 11-O-demethyl-23,27-didemethoxy-, monosodium salt (28S)- including: 2 synonyms/identifiers.
TY - JOUR. T1 - Calcium transport into the vacuole of oat roots. Characterization of H+/Ca2+ exchange activity.. AU - Schumaker, Karen S. AU - Sze, H.. PY - 1986/9/15. Y1 - 1986/9/15. N2 - Calcium (Ca2+) is sequestered into vacuoles of oat root cells through a H+/Ca2+ antiport system that is driven by the proton-motive force of the tonoplast H+-translocating ATPase. The antiport has been characterized directly by imposing a pH gradient in tonoplast-enriched vesicles. The pH gradient was imposed by diluting K+-loaded vesicles into a K+-free medium. Nigericin induced a K+/H+ exchange resulting in a pH gradient of 2 (acid inside). The pH gradient was capable of driving 45Ca2+ accumulation. Ca2+ uptake was tightly coupled to H+ loss as increasing Ca2+ levels progressively dissipated the steady state pH gradient. Ca2+ uptake displayed saturation kinetics with a Km(app) for Ca2+ of 10 microM. The relative affinity of the antiporter for transport of divalent cations was Ca2+ greater than Sr2+ greater ...
1. The properties of membrane vesicles from the extreme thermophile Bacillus caldolyticus were investigated. 2. Vesicles prepared by exposure of spheroplasts to ultrasound contained cytochromes a, b and c, and at 50°C they rapidly oxidized NADH and ascorbate in the presence of tetramethyl-p-phenylenediamine. Succinate and l-malate were oxidized more slowly, and dl-lactate, l-alanine and glycerol 1-phosphate were not oxidized. 3. In the absence of proton-conducting uncouplers the oxidation of NADH was accompanied by a net translocation of H+ into the vesicles. Hydrolysis of ATP by a dicyclohexylcarbodi-imide-sensitive adenosine triphosphatase was accompanied by a similarly directed net translocation of H+. 4. Uncouplers (carbonyl cyanide p-trifluoromethoxyphenylhydrazone or valinomycin plus NH4+) prevented net H+ translocation but stimulated ATP hydrolysis, NADH oxidation and ascorbate oxidation. The last result suggested an energy-conserving site in the respiratory chain between cytochrome c ...
The P2X(7) receptor (P2X(7)R) is an ATP-gated ion channel expressed by monocytes and macrophages. To directly address the role of this receptor in interleukin (IL)-1 beta post-translational processing, we have generated a P2X(7)R-deficient mouse line. P2X(7)R(-/-) macrophages respond to lipopolysaccharide and produce levels of cyclooxygenase-2 and pro-IL-1 beta comparable with those generated by wild-type cells. In response to ATP, however, pro-IL-1 beta produced by the P2X(7)R(-/-) cells is not externalized or activated by caspase-1. Nigericin, an alternate secretion stimulus, promotes release of 17-kDa IL-1 beta from P2X(7)R(-/-) macrophages. In response to in vivo lipopolysaccharide injection, both wild-type and P2X(7)R(-/-) animals display increases in peritoneal lavage IL-6 levels but no detectable IL-1. Subsequent ATP injection to wild-type animals promotes an increase in IL-1, which in turn leads to additional IL-6 production; similar increases did not occur in ATP-treated, LPS-primed ...
The mechanism of unidirectional transport of ornithine (i.e. in the absence of a counter-metabolite) has been investigated in proteoliposomes reconstituted with the ornithine carrier purified from rat liver mitochondria. The efflux of [3H]ornithine from proteoliposomes was stimulated by the addition of H+ (but not of other cations) to the incubation medium . On keeping the pH in the compartment containing ornithine constant at 8.0, the flux of ornithine into or out of the proteoliposomes increased on decreasing the pH in the opposite compartment from 8.0 to 6.0. Ornithine influx was also stimulated when a higher H+ concentration was generated inside the vesicles relative to the outside by the K+/H+ exchanger nigericin in the presence of an outwardly directed K+ gradient. A valinomycin-induced electrogenic flux of K+ did not affect ornithine transport in the absence of a counter-metabolite. Furthermore, changes in fluorescence of the pH indicator pyranine, included inside the proteoliposomes, ...
Materials.d-[1-14C]Mannitol (57.0 mCi/mmol) was purchased from Amersham Biosciences Inc. (Piscataway, NJ). EC, ECG, EGCG, (+)-catechin (Fig. 1), colchicine, meta-phosphoric acid, and BSO, phloridzin, glucose, phloretin, glycyl-sarcosine, sodium azide, 2-de-oxy-d-glucose, nigericin, FCCP, and benzoic acid were obtained from Sigma-Aldrich (St. Louis, MO). MK-571 was a gift from Dr. A. W. Ford-Hutchinson (Merck-Frosst Centre for Therapeutic Research, Pointe Claire-Dorval, QC, Canada), and PSC833 (valspodar), was a gift from Novartis (Basel, Switzerland). EAG5, MRP2-specific antibody, was provided by Dr. Keppler (Deutsches Krebsforschungszentrum, Heidelberg, Germany). Glutathione assay kit was from Calbiochem (La Jolla, CA). Trifluoroacetic acid was of spectrophotometric grade from Aldrich Chemical Co. (Milwaukee, WI), fetal bovine serum from Atlanta Biologicals (Norcross, GA), and Hanks balanced salt solution (HBSS) and other cell culture medium components were obtained from Cellgro Mediatech, ...
TY - JOUR. T1 - The level of stromal ATP regulates translation of the D1 protein in isolated chloroplasts. AU - Kuroda, Hiroshi. AU - Inagaki, Noritoshi. AU - Satoh, Kimiyuki. PY - 1992/1/1. Y1 - 1992/1/1. N2 - The synthesis of the D1 subunit of the reaction center of photosystem II is light-dependent in isolated chloroplasts. The mechanism of the regulation by light was analyzed using spinach chloroplasts. The light-regulated synthesis of the D1 protein was prevented by the addition of atrazine and the dependence on the concentration of atrazine of the inhibition was practically identical with that of the inhibition of photosynthetic electron transport in photosystem II, as measured by the photoreduction of 2,6-dichlorophenol indophenol. Inhibitors of photosynthetic phosphorylation, such as phloridzin, nigericin and carbonyl cyanide m-chlorophenylhydrazone, also inhibited the light-dependent synthesis of the D1 protein. Determination of the levels of ATP in chloroplasts and the rates of ...
Ca2+ uptake into Ehrlich ascites tumor cells was studied at 0°C in the presence of mitochondrial inhibitors, conditions that minimized complications caused by sequestration of Ca2+ into organelles or by excretion. Under these conditions Ruthenium Red inhibited Ca2+ uptake, but other previously implicated ions, such as Pi or Mg2+, had no effect. Valinomycin either inhibited or slightly stimulated Ca2+ uptake depending on the presence of excess K+ on the outside or inside of the cell, respectively. Nigericin inhibited Ca2+ transport. Based on these data we propose an electrogenic uptake of Ca2+, possibly via a Ca2+/H+ antiport mechanism. The observation that glucose inhibited Ca2+ uptake suggested that in Ehrlich ascites tumor cells an energy-driven Ca2+ expulsion mechanism is operative, similar to that in erythrocytes. Plasma membrane preparations of ascites tumor cells were found to contain a Ca2+-dependent ATPase. These preparations, when incorporated into liposomes in an inside-out orientation,
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The effects of pH gradients on the uptake and distribution of C14-procaine and lidocaine in intact and desheathed sciatic nerve trunks.:
Betegnelsen humørforstyrrelser beskriver en rekke tilstander som påvirker vår evne til å regulere humør. Lær hva forskningen sier om effektene av CBD på humøret.
Up until now Ive merely glanced at the FoodBabes unscientific mumbo jumbo and chemically implausible claims about a variety of
Up until now Ive merely glanced at the FoodBabes unscientific mumbo jumbo and chemically implausible claims about a variety of
Read "Influence of electrochemical proton gradient on electron flow in photosystem I of pea leaves, Russian Journal of Plant Physiology" on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.
Individual bacteria use multiple electron transport chains, often simultaneously. Bacteria can use a number of different electron donors, a number of different dehydrogenases, a number of different oxidases and reductases, and a number of different electron acceptors. For example, E. coli (when growing aerobically using glucose as an energy source) uses two different NADH dehydrogenases and two different quinol oxidases, for a total of four different electron transport chains operating simultaneously.. A common feature of all electron transport chains is the presence of a proton pump to create a transmembrane proton gradient. Bacterial electron transport chains may contain as many as three proton pumps, like mitochondria, or they may contain only one or two. They always contain at least one proton pump.. In the present day biosphere, the most common electron donors are organic molecules. Organisms that use organic molecules as an energy source are called organotrophs. Organotrophs (animals, ...
Prokaryotic and eukaryotic proteins cluster separately but probably function with the same polarity by similar mechanisms. These proteins are secondary carriers which utilize the pmf and function by H antiport (for metal efflux). One member, CzcD of Bacillus subtilis, has been shown to exchange the divalent cation (Zn2+ or Cd2+ ) for two monovalent cations (K+ and H+ ) in an electroneutral process energized by the transmembrane pH gradient (Guffanti et al., 2002). Another, ZitB of E. coli (TC #2.A.4.1.4), has been reconstituted in proteoliposomes and studied kinetically (Chao and Fu, 2004a). It appears to function by simple Me2+:H antiport with a 1:1 stoichiometry.. Montanini et al (2007) have conducted phylogenetic analysis of CDF family members. Their analysis revealed three major and two minor phylogenetic groups. They suggest that the three major groups segregated according to metal ion specificity: (1) Mn2+ , (2) Fe2+ and Zn2+ as well as other metal ions, and (3) Zn2+ plus other metals, but ...