Inhibitors of ABC Transporters and Biophysical Methods to Study their Activity

Bartosiewicz, Dominika; Krasowska, Anna

doi:10.1515/znc-2009-5-625

Cited by 13 publications

(7 citation statements)

References 34 publications

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“…Consequently, inhibition of calcium binding by a phenothiazine inhibits calcium signalling processes and therefore the processes of post-phagocytosis should be affected. Calcium signalling pathways of eukaryotic cells are affected by inhibitors of calcium transport [41][42][43][44][45][46][47][48][49]. As would be expected, phenothiazines are potent inhibitors of calcium transport [50].…”

Section: How Does Thioridazine Cure Extensively Drug-resistant Tubercmentioning

confidence: 83%

Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections

Amaral

Viveiros

2012

International Journal of Antimicrobial Agents

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Section: How Does Thioridazine Cure Extensively Drug-resistant Tubercmentioning

confidence: 83%

Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections

Amaral

Viveiros

2012

International Journal of Antimicrobial Agents

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“…If so, it must be inhibited. Note that R123 (rhodamine 123) is not only a probe of potential, but is also frequently employed to test for the presence of such transporters [87].…”

Section: Forces: Mitochondrial Membrane Potentialmentioning

confidence: 99%

Assessing mitochondrial dysfunction in cells

Brand¹,

Nicholls²

2011

Biochemical Journal

213

301

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Assessing mitochondrial dysfunction requires definition of the dysfunction to be investigated. Usually, it is the ability of the mitochondria to make ATP appropriately in response to energy demands. Where other functions are of interest, tailored solutions are required. Dysfunction can be assessed in isolated mitochondria, in cells or in vivo, with different balances between precise experimental control and physiological relevance. There are many methods to measure mitochondrial function and dysfunction in these systems. Generally, measurements of fluxes give more information about the ability to make ATP than do measurements of intermediates and potentials. For isolated mitochondria, the best assay is mitochondrial respiratory control: the increase in respiration rate in response to ADP. For intact cells, the best assay is the equivalent measurement of cell respiratory control, which reports the rate of ATP production, the proton leak rate, the coupling efficiency, the maximum respiratory rate, the respiratory control ratio and the spare respiratory capacity. Measurements of membrane potential provide useful additional information. Measurement of both respiration and potential during appropriate titrations enables the identification of the primary sites of effectors and the distribution of control, allowing deeper quantitative analyses. Many other measurements in current use can be more problematic, as discussed in the present review.

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“…[112][113][114][115][116]). Metabolising yeast cells can also accumulate it [117][118][119][120][121]. We note that the extent of fluorescence is not necessarily fully linear with concentration because of dye stacking [108; 109; 122](and see [123]) but is at least assumed to be more or less monotonic.…”

Section: Sybr Green I Uptake Measurement On Fixed Keio Strainsmentioning

confidence: 99%

Involvement of multiple influx and efflux transporters in the accumulation of cationic fluorescent dyes byEscherichia coli

Jindal¹,

Yang

Day

et al. 2019

Preprint

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We used high-throughput flow cytometry to assess the ability of individual gene knockout strains ofE colito take up two membrane-permeable, cationic fluorescent dyes, viz the carbocyanine diS-C3(5) and the DNA dye SYBR Green. Individual strains showed a large range of distributions of uptake. The range of modal steady-state uptakes for the carbocyanine between the different strains was 36-fold. Knockouts of the ATP synthase α- and β-subunits greatly inhibited uptake, implying that most uptake was ATP-driven rather than being driven by say a membrane potential. Dozens of transporters changed the steady-state uptake of the dye by more than 50% with respect to that of the wild type, in both directions (increased or decreased); knockouts in known influx and efflux transporters behaved as expected, giving confidence in the general strategy. Many of the knockouts with the most reduced uptake were transporter genes of unknown function (‘y-genes’). Similarly, several overexpression variants in the ‘ASKA’ collection had the anticipated, opposite effects. Similar findings were made with SYBR Green (the range being some 69-fold), though despite it too containing a benzimidazole motif there was negligible correlation between its uptake and that of the carbocyanine when compared across the various strains. Overall, we conclude that the uptake of these dyes may be catalysed by a great many transporters of possibly broad and presently unknown specificity. This casts serious doubt upon the use of such dyes as quantitative stains for representing either bioenergetic parameters or the amount of cellular DNA in unfixed cells (in vivo). By contrast, it opens up their potential use as transporter assay substrates in high-throughput screening.

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Inhibitors of ABC Transporters and Biophysical Methods to Study their Activity

Abstract: inhibitors of ABC proteins and biophysical methods which could be used for measuring the ABC transporters activity.

Cited by 13 publications

References 34 publications

Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections

Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections

Assessing mitochondrial dysfunction in cells

Involvement of multiple influx and efflux transporters in the accumulation of cationic fluorescent dyes byEscherichia coli

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