Interaction of sanguinarine and its dihydroderivative with the Na+/K+-ATPase. Complex view on the old problem

Janovská, Marika; Kubala, Martin; Šimánek, Vilı́m; Ulrichová, Jitka

doi:10.1016/j.toxlet.2010.03.1114

Cited by 16 publications

(11 citation statements)

References 19 publications

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“…Our findings may contribute to the elucidation of a more than 30 years old enigma: the related QBA sanguinarine inhibits NKA as well NKP in a variety of tissues [46,47,48,60,61,62] with similar dose dependence as observed here with CET in LECs. Some studies have shown that sanguinarine increases the in vitro dissociation constant of ouabain by 10 fold in guinea pig atrium preparations and exerts an inotropic effect [63], whereas inhibition of 3 H-ouabain binding in beef heart NKA is due to interaction with the ouabain receptor although a conformational change due to direct action was not excluded [46].…”

Section: Discussionsupporting

confidence: 77%

Canonical Bcl-2 Motifs of the Na+/K+ Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

Lauf

Heiny

Meller

et al. 2013

Cell Physiol Biochem

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Background/Aims: Chelerythrine [CET], a protein kinase C [PKC] inhibitor, is a prop-apoptotic BH3-mimetic binding to BH1-like motifs of Bcl-2 proteins. CET action was examined on PKC phosphorylation-dependent membrane transporters (Na⁺/K⁺ pump/ATPase [NKP, NKA], Na⁺-K⁺-2Cl⁺ [NKCC] and K⁺-Cl^- [KCC] cotransporters, and channel-supported K⁺ loss) in human lens epithelial cells [LECs]. Methods: K⁺ loss and K⁺ uptake, using Rb⁺ as congener, were measured by atomic absorption/emission spectrophotometry with NKP and NKCC inhibitors, and Cl^- replacement by NO₃^ˉ to determine KCC. ³H-Ouabain binding was performed on a pig renal NKA in the presence and absence of CET. Bcl-2 protein and NKA sequences were aligned and motifs identified and mapped using PROSITE in conjunction with BLAST alignments and analysis of conservation and structural similarity based on prediction of secondary and crystal structures. Results: CET inhibited NKP and NKCC by >90% (IC₅₀ values ∼35 and ∼15 µM, respectively) without significant KCC activity change, and stimulated K⁺ loss by ∼35% at 10-30 µM. Neither ATP levels nor phosphorylation of the NKA α1 subunit changed. ³H-ouabain was displaced from pig renal NKA only at 100 fold higher CET concentrations than the ligand. Sequence alignments of NKA with BH1- and BH3-like motifs containing pro-survival Bcl-2 and BclXl proteins showed more than one BH1-like motif within NKA for interaction with CET or with BH3 motifs. One NKA BH1-like motif (ARAAEILARDGPN) was also found in all P-type ATPases. Also, NKA possessed a second motif similar to that near the BH3 region of Bcl-2. Conclusion: Findings support the hypothesis that CET inhibits NKP by binding to BH1-like motifs and disrupting the α₁ subunit catalytic activity through conformational changes. By interacting with Bcl-2 proteins through their complementary BH1- or BH3-like-motifs, NKP proteins may be sensors of normal and pathological cell functions, becoming important yet unrecognized signal transducers in the initial phases of apoptosis. CET action on NKCC1 and K⁺ channels may involve PKC-regulated mechanisms; however, limited sequence homologies to BH1-like motifs cannot exclude direct effects.

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Section: Discussionsupporting

confidence: 77%

Canonical Bcl-2 Motifs of the Na+/K+ Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

Lauf

Heiny

Meller

et al. 2013

Cell Physiol Biochem

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“…Pharmacokinetic studies of sanguinarine in rats have suggested that oral sanguinarine bioavailability is low with 42% of 3 H‐sanguinarine remaining in the gastrointestinal tract and a low sanguinarine to DHSG plasma concentration ratio suggesting most sanguinarine is metabolized to DHSG during or soon after its absorption from the gastrointestinal tract with both compounds having a T max of 2 hours (Vecera et al, ). As DHSG does not appear to interact with the Na + /K + ‐ATPase pump, it has been argued that oral sanguinarine, due to its poor absorption and rapid metabolism to DHSG, should have a limited ability for in vivo Na + /K + ‐ATPase inhibition (Janovská, Kubala, Šimánek, Ulrichová ). Patients with epidemic dropsy have significantly elevated hydroxybutyrate dehydrogenase levels (an enzyme found in myocardium) of 165 U l −1 compared to controls 97 U l −1 , this remaining elevated 1 month after AO exposure cessation at 128 U l −1 .…”

Section: Does Sanguinarine Cause Epidemic Dropsy?mentioning

confidence: 99%

Assessing the risk of epidemic dropsy from black salve use

Croaker

King

Pyne

et al. 2018

J of Applied Toxicology

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Epidemic dropsy is a potentially life-threatening condition resulting from the ingestion of argemone oil derived from the seeds of Argemone mexicana Linn. Exposure to argemone oil is usually inadvertent, arising from mustard cooking oil adulteration. Sanguinarine, an alkaloid present in argemone oil, has been postulated as a causative agent with the severity of epidemic dropsy correlating with plasma sanguinarine levels. Cases of epidemic dropsy have also been reported following the topical application of argemone containing massage oil. Black salve, a topical skin cancer therapy also contains sanguinarine, but at significantly higher concentrations than that reported for contaminated massage oil. Although not reported to date, a theoretical risk therefore exists of black salve inducing epidemic dropsy. This literature review explores the presentation and pathophysiology of epidemic dropsy and assesses the risk of it being induced by black salve.

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“…The CET structure-related sanguinarines have been known for a long time to inhibit the NKP in a variety of tissue preparations [11,12,13,14,15,16,17], without an explanation for this effect. Sequence homologies between BH1-like motifs originally reported to bind CET in Bcl-Xl proteins and found in the cytoplasmic aspect of the crystal structure of the NKP led to the hypothesis that CET may inhibit the NKP function through these BH1 motifs [10].…”

Section: Introductionmentioning

confidence: 99%

Surface-Enhanced Raman Spectroscopy (SERS) Tracking of Chelerythrine, a Na⁺/K⁺Pump Inhibitor, into Cytosol and Plasma Membrane Fractions of Human Lens Epithelial Cell Cultures

Dorney

Sizemore

Alqahtani

et al. 2013

Cell Physiol Biochem

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Background/Aims: The quaternary benzo-phenanthridine alkaloid (QBA) chelerythrine (CET) is a pro-apoptotic drug and Na⁺/K⁺ pump (NKP) inhibitor in human lens epithelial cells (HLECs). In order to obtain further insight into the mechanism of NKP inhibition by CET, its sub-cellular distribution was quantified in cytosolic and membrane fractions of HLEC cultures by surface-enhanced Raman spectroscopy (SERS). Methods: Silver nanoparticles (AgNPs) prepared by the Creighton method were concentrated, and size-selected using a one-step tangential flow filtration approach. HLECs cultures were exposed to 50 μM CET in 300 mOsM phosphate-buffered NaCl for 30 min. A variety of cytosolic extracts, crude and purified membranes, prepared in lysing solutions in the presence and absence of a non-ionic detergent, were incubated with AgNPs and subjected to SERS analysis. Determinations of CET were based on a linear calibration plot of the integrated CET SERS intensity at its 659 cm^-1 marker band as a function of CET concentration. Results: SERS detected chemically unaltered CET in both cytosol and plasma membrane fractions. Normalized for protein, the CET content was some 100 fold higher in the crude and purified plasma membrane fraction than in the soluble cytosolic extract. The total free CET concentration in the cytosol, free of membranes or containing detergent-solubilized membrane material, approached that of the incubation medium of HLECs. Conclusion: Given a negative membrane potential of HLECs the data suggest, but do not prove, that CET may traverse the plasma membrane as a positively charged monomer (CET⁺) accumulating near or above passive equilibrium distribution. These findings may contribute to a recently proposed hypothesis that CET binds to and inhibits the NKP through its cytosolic aspect.

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Interaction of sanguinarine and its dihydroderivative with the Na+/K+-ATPase. Complex view on the old problem

Cited by 16 publications

References 19 publications

Canonical Bcl-2 Motifs of the Na<sup>+</sup>/K<sup>+</sup> Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

Canonical Bcl-2 Motifs of the Na<sup>+</sup>/K<sup>+</sup> Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

Assessing the risk of epidemic dropsy from black salve use

Surface-Enhanced Raman Spectroscopy (SERS) Tracking of Chelerythrine, a Na⁺/K⁺Pump Inhibitor, into Cytosol and Plasma Membrane Fractions of Human Lens Epithelial Cell Cultures

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Interaction of sanguinarine and its dihydroderivative with the Na+/K+-ATPase. Complex view on the old problem

Cited by 16 publications

References 19 publications

Canonical Bcl-2 Motifs of the Na<sup>+</sup>/K<sup>+</sup> Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

Canonical Bcl-2 Motifs of the Na<sup>+</sup>/K<sup>+</sup> Pump Revealed by the BH3 Mimetic Chelerythrine: Early Signal Transducers of Apoptosis?

Assessing the risk of epidemic dropsy from black salve use

Surface-Enhanced Raman Spectroscopy (SERS) Tracking of Chelerythrine, a Na+/K+Pump Inhibitor, into Cytosol and Plasma Membrane Fractions of Human Lens Epithelial Cell Cultures

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Surface-Enhanced Raman Spectroscopy (SERS) Tracking of Chelerythrine, a Na⁺/K⁺Pump Inhibitor, into Cytosol and Plasma Membrane Fractions of Human Lens Epithelial Cell Cultures