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Membrane Transport
Published in Lelio G. Colombetti, Biological Transport of Radiotracers, 2020
These ionophores have also been shown to exchange ions in biological systems. In red cells, the use of ionophores indicated that Cl- transport occurs according to a “silent” mechanism (see below). K+ release from red cells is measured (see Figure 10). Adding valinomycin did not significantly speed up K+ flux, because there was no net Cl- efflux to provide electroneutrality. Adding the proton carrier FCCP did enhance K+ efflux because K+ could be exchanged for protons. Adding nigericin instead did the same as the combination of valinomycin and FCCP because nigericin by itself can act as a K+–H+ exchange carrier.
Palytoxin
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Jiri Patocka, Qinghua Wu, Kamil Kuca
Pelin et al. [56] have demonstrated that Na+ overload is the crucial step in mediating overproduction of reactive oxygen species (ROS) and cell death in human HaCaT keratinocytes, tentatively explaining PLTX-induced skin irritant effects. In their study, the molecular mechanisms of ROS production induced by PLTX-mediated Na+ intracellular overload have been investigated. In HaCaT cells, PLTX exposure caused accumulation of superoxide anion, but not of nitric oxide or peroxynitrite/hydroxyl radicals. Even if reverse-transcription polymerase chain reaction (RT-PCR) and Western blot analysis revealed an early NOX-2 and iNOS gene and protein overexpressions, their active involvement seemed to be only partial since selective inhibitors did not completely reduce or production. A significant role of other enzymes (COX-1, COX-2, XO) was not evidenced. Nigericin, which counteracts Na+-mediated H+-imbalance, dissipating Delta pH across mitochondrial inner membrane, and the uncouplers DNP significantly reduced O-2(−) production. These inhibitions were synergistic when co-exposed with complex-I inhibitor rotenone. These results suggest a novel mechanism of O-2(−) production induced by PLTX-mediated ionic imbalance. Indeed, the H+ intracellular overload that follows PLTX-induced intracellular Na+ accumulation, could enhance Delta pH across mitochondrial inner membrane, which seems to be the driving force for O-2(−) production by reversing mitochondrial electron transport.
Activation of Human Inflammatory Cells
Published in William S. Lynn, Inflammatory Cells and Lung Disease, 2019
The data shown in Figure 1B indicate that the ionophores and lecithin analogues which so markedly alter leukocyte functions are also effective in erythrocytes. The Ca+ + ionophore, A-23187, causes a reversible (depending on the concentration) hyperpolarization of intact erythrocytes to the same extent ( − 40 mV) as does valinomycin at low K+ concentration. This uptake of diO-C3[5] in phosphate buffered saline requires external Ca+ + (Km is about 1 µM) and is completely reversed by adding the Ca+ + chelator, ethylenediaminetetracetic acid, or other organic cations, e.g., trifluoropyrazine, or by raising the external K+ concentration. In fact, with 100 mM K+ and valinomycin 0.5 µM, no hyperpolarization occurs with addition of the ionophore (Figure 1B). However, in nonsodium buffers, i.e., isotonic choline chloride or sucrose, large anions at low concentrations, including arachidonic acid, lasalocid, ethylene diamine tetracetic acid, A-23187, oleic acid, all potentiate the ability of valinomycin to hyperpolarize erythrocytes, probably by serving as cationophores. At higher concentrations of the anions, depolarization, i.e., loss of the dye, occurs (Figure 2). Since similar hyperpolarization-depolarization cycles occur upon addition of ionophores, e.g., nigericin and monensin, in absence of external cations or anions (isotonic sucrose), it is clear that in erythrocytes the observed membrane potential cycles under these conditions represent progressive changes in permeability of both internal ions (Cl− and K +).
Effect of antibiotic monensin on cell proliferation and IGF1R signaling pathway in human colorectal cancer cells
Published in Annals of Medicine, 2023
Youping Zhou, Youlin Deng, Jing Wang, Zhengjian Yan, Qiang Wei, Jixing Ye, Junhui Zhang, Tong-Chuan He, Min Qiao
The patients with colorectal cancer at stage IV accounts for about 20-25% of total patients, whose 5-year survival rate only reaches about 10% and much less than that at stage I-II, which ranges from 80% to 90% [1,3]. This is due to the limitations of chemotherapy resulting from drug resistance and organ toxicities [4,5]. Thus, searching and developing a novel effective therapeutic agency become critical to treat colorectal cancer. Various ionophore antibiotics, including monensin, salinomycin and nigericin, have been reported to overcome multidrug resistance in different types of cancer cells [44,45], Present study showed that monensin effectively inhibited cell proliferation as well as migration, and induced apoptosis as well as cell cycle arrest in RKO and HCT-116. Similar results have been reported in other researches with respect to various kinds of cancers, including prostate, ovarian, lung, glioma, renal, myeloma, colorectal cancer cell lines and so on [9–20]. Furthermore, a recent study indicated that malignant neoplasm showed more sensitive to monensin than their nonmalignant counterparts [9]. Simultaneously, as an antibiotic, monensin has represented a positive safety profile in veterinary medicine and been applied in cattle and poultry feed for nearly 50 years [8,20]. Given the features described above, monensin has the potential to be repurposed as the novel therapeutic agency against tumor, including colorectal cancer.
Fraxinol attenuates LPS-induced acute lung injury by equilibrating ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas and inhibiting NLRP3
Published in Pharmaceutical Biology, 2022
Yan Wu, Xin Yang, Yuanyuan Ju, Fei Zhao
Raw264.7 cells were purchased from American Type Culture Collection (Manassas, VA, USA) and cultured in 90% Dulbecco’s Modified Eagle’s Medium (Gibco, Grand Island, NY, USA) with 10% foetal bovine serum (Hyclone, Logan, UT, USA). The culture conditions were 95% air, 5% CO2 at 37 °C. For inducing a cell model of ALI, Raw264.7 cells were treated by 100 ng/mL LPS for 6 h. The cells were then treated by different concentrations of fraxinol (5, 10, and 25 μM) for 48 h. The cells were cultured with 10−5 mol/L A779 (MedChemExpress) and 10−5 mol/L MLN-4760 (MedChemExpress) for inhibition of MasR and ACE2. Nigericin with concentration of 10 µM was used to treat cells for activation of NLRP3.
Senkyunolide A inhibits the progression of osteoarthritis by inhibiting the NLRP3 signalling pathway
Published in Pharmaceutical Biology, 2022
Minglei Shao, Dongwei Lv, Kai Zhou, Haijun Sun, Zhitao Wang
In addition, we detected apoptosis and proliferation of chondrocytes after treatment with SenA and nigericin. The EdU-positive cells in IL-1β + SenA + Nig group were significantly less than that of IL-1β + SenA group, indicating that nigericin inhibited the proliferation of chondrocytes (Figure 4(G)). Nigericin treatment significantly promoted apoptosis of chondrocytes compared to IL-1β + SenA group (Figure 4(H)). Together, these results suggested that SenA plays a protective role in mice chondrocytes by inhibiting NLRP3 signalling pathways.