Where Cancer and Bacteria Meet
Ananda M. Chakrabarty, Arsénio M. Fialho in Microbial Infections and Cancer Therapy, 2019
Ionophores promote ion transport across lipid bilayers and include a large number of naturally occurring molecules. External disruption of the ion permeability of membranes disturbs the normal ion balance, a property that can be exploited in the induction of cell death (apoptosis, autophagy, or necrosis), including that of tumor cells, or the elimination of harmful microorganisms. While anion-selective ionophores (anionophores) are much less common than cationophores, they have attracted intense interest over the last two decades. Anionophores are natural products that facilitate transmembrane anion transport across phospholipid bilayers [54]. This capability is crucial for the maintenance of the concentration gradients that form the basis for signaling and cellular regulation.
Avian coccidiosis: a disturbed host-parasite relationship to be restored
G. F. Wiegertjes, G. Flik in Host-Parasite Interactions, 2004
Strains of lower virulence could be selected from natural populations by harvesting oocysts 1–2 days prior to the peak oocyst shedding. These strains were called precocious and related to a genetic trait of early gametogenesis, by omitting one of the mitotic replication stages. The reduction of the proliferative capacity made these strains suitable as vaccines with a better safety margin. Especially for use in older birds such as the breeders these vaccines have been widely accepted and applied (Williams, 2002). Nobilis COX ATM™ is somewhat unique in its concept. The strains have been selected from field strains for a naturally acquired lower proliferative capacity comparable with the precocious strains. These strains however were also selected for a relative tolerance to widely used ionophores. The ionophores are not only utilized as anti-coccidials but also demonstrate some bacteriostatic activity. The combination of these aspects made it possible to apply ionophores in conjunction with a live vaccine. The widely existing resistance of Eimeria field strains for the common drugs might justify the use of this vaccine under specific conditions (Vermeulen et al., 2001).
Assisted oocyte activation Current understanding, practice, and future perspectives
David K. Gardner, Ariel Weissman, Colin M. Howles, Zeev Shoham in Textbook of Assisted Reproductive Techniques, 2017
In the published literature, reported fertilization and pregnancy rates following AOA are highly variable, most likely due to the heterogenic and low number of patients recruited in the vast majority of studies. Furthermore, differences in patient baseline characteristics coupled with the fact that different activating agents have been used make it hard to compare different reports (83, 99). Remarkably, even AOA protocols used throughout the published literature diverge in the ionophore concentra- tion used, duration of ionophore exposure, time of iono- phore exposure following ICSI, and number of ionophore exposures (83). Thus, it appears likely that while AOA is a significantly effective method with which to resolve cases of extreme oocyte activation deficiency, current AOA protocols may not necessarily be effective for all groups of patients. Indeed, Ebner et al. (100) suggested that success following ionophore treatment is related to fertilization rates in previous cycles, with AOA present- ing with the best results in patients with a history of less than 30% fertilization in a previous ICSI cycle and with earlier studies providing a similar outlook (98, 100).
A retrospective analysis of artificial oocyte activation in patients with low or no fertilisation in intracytoplasmic sperm injection cycles
Published in Journal of Obstetrics and Gynaecology, 2022
Kevin K. W. Lam, Jacki Y. Y. Wong, Tak-Ming Cheung, Raymond H. W. Li, Ernest H. Y. Ng, William S. B. Yeung
Calcium ionophores are lipid soluble molecules. They transport calcium ions across the cell membrane which in turn induce a single transient rise in intracellular calcium level. When used for AOA, the concentration of A23187 varies from 5–10 µM (Montag et al. 2012; Lv et al. 2020). Although the concentration of the ready-to-use A23187 reagent is not disclosed by the manufacturer, it has been shown to induce a single rise in intracellular calcium to a peak within two minutes (Nikiforaki et al. 2016). The safety and efficacy of the ready-to-use A23187 has been proven in previous studies (Ebner et al. 2012; Caglar et al. 2015; Ebner et al. 2015). Exposure of A23187 in conjunction with calcium chloride injection together with spermatozoon has also been reported (Vanden Meerschaut et al. 2012). Our data indicated that the performance of two protocols were comparable. The observation is understandable as the injection of calcium chloride and the subsequent A23187 exposure might increase the intracellular calcium concentration to a level higher than that using A23187 alone, both protocols could not generate calcium oscillations (Nikiforaki et al. 2016). To the best of our knowledge, there is no commercially available mouse embryo-tested calcium chloride for AOA. The calcium chloride solution was mainly prepared from research grade chemicals (Vanden Meerschaut et al. 2012; Nikiforaki et al. 2016), the safety of which is in doubt. Based on the current data, AOA should be performed without the concomitant injection of calcium chloride.
An overview of the recent progress in Middle East Respiratory Syndrome Coronavirus (MERS-CoV) drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Mahmoud Kandeel
A cell-based enzyme-linked immunosorbent assay (ELISA) has been used to screen and evaluate many FDA-approved drugs for their ability to target MERS-CoV. The drugs include neurotransmitter blockers, DNA synthesis/repair inhibitors, lipid and sterol metabolism antagonists, estrogen receptor antagonists, protein-processing blockers, ion transport blockers, cytoskeletal drugs (particularly tubulin), kinase-signaling blockers, and apoptosis inhibitors [22]. Despite not having a clear connection to CoVs, two groups of pharmaceuticals – antiparasitics and antibiotics – showed effectiveness against MERS-CoV infection. Specifically, nocodazole acted on the cytoskeleton to halt spindle development. It is an antimitotic drug originally developed to fight cancer, but studies have shown that it is also highly effective against MERS-CoV [22,130]. Two of nine ion channel blockers tested, monensin and salinomycin sodium, had inhibitory effects against MERS-CoV. There is experimental evidence that MERS-CoV is vulnerable to ionophore activities [131]. The EC50 and CC50 values for monensin were 3.2 and greater than 20 µM, respectively [131]. Thus, it was effective against MERS-CoV at low concentrations and had little toxicity.
Ca2+ mediates extracellular vesicle biogenesis through alternate pathways in malignancy
Published in Journal of Extracellular Vesicles, 2020
Jack Taylor, Iman Azimi, Gregory Monteith, Mary Bebawy
Using pharmacological modulators of Ca2+ release together with topographical AFM analysis we show that intracellular calcium mobilization is required for plasma membrane EV biogenesis. The Ca2+ ionophore, A23187 (1 µM) was used to study the effect of increasing intracellular Ca2+ on malignant (MCF-7 and Dx) cell and non-malignant (hCMEC-D3) cell vesiculation (Figure 1). Ca2+ ionophores mobilize Ca2+ through the translocation of Ca2+-ionophore complexes across the plasma membrane, activation of native plasma membrane Ca2+ channels, and via mobilization of Ca2+ from the ER [58].
Related Knowledge Centers
- Catalysis
- Chelation
- Chemistry
- Lipid Bilayer
- Valinomycin
- Liposome
- Cell Membrane
- Ion
- Ion Transporter
- Nigericin