Effects of the PKC inhibitors chelerythrine and bisindolylmaleimide I (GF 109203X) on delayed rectifier K+ currents

Harmati, Gábor; Papp, Ferenc; Szentandrássy, Norbert; Bárándi, László; Ruzsnavszky, Ferenc; Horváth, Balázs; Bányász, Tamás; Magyar, János; Panyi, György; Krasznai, Zoltán; Nánási, Péter P.

doi:10.1007/s00210-010-0584-8

Cited by 16 publications

(7 citation statements)

References 23 publications

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“…PMA treatment augmentation of hNav1.7 resurgent current amplitude was prevented by pretreatment with the PKC antagonists Bis I or chelerythrine at the concentration of 1 lM (Fig. 1) [23,10]. In addition, 1 lM PMA also significantly shifted the peak voltage, the voltage where peak resurgent current was measured (from À39 mV for control to À33 mV for PMA treated; Suppl.…”

Section: Resultsmentioning

confidence: 90%

Protein kinase C enhances human sodium channel hNav1.7 resurgent currents via a serine residue in the domain III–IV linker

et al. 2014

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Resurgent sodium currents likely play a role in modulating neuronal excitability. Here we studied whether protein kinase C (PKC) activation can increase resurgent currents produced by the human sodium channel hNav1.7. We found that a PKC agonist significantly enhanced hNav1.7-mediated resurgent currents and this was prevented by PKC antagonists. The enhancing effects were replicated by two phosphorylation-mimicking mutations and were prevented by a phosphorylation-deficient mutation at a conserved PKC phosphorylation site (Serine 1479). Our results suggest that PKC can increase sodium resurgent currents through phosphorylation of a conserved Serine residue located in the domain III–IV linker of sodium channels.

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Section: Resultsmentioning

confidence: 90%

Protein kinase C enhances human sodium channel hNav1.7 resurgent currents via a serine residue in the domain III–IV linker

et al. 2014

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“…The structural similarity between bisindolylmaleimides, chelerythine and staurospoorine suggested that bisindolylmaleimides may be a competitive inhibitor with respect to ATP. The inhibition of PKC by bisindolylmaleimides was demonstrated to be highly dependent on the ATP concentration [4,29]. GF 109203X inhibited collagenand alpha-thrombin-induced platelet aggregation as well as collagen-triggered ATP secretion.…”

Section: Discussionmentioning

confidence: 99%

PKC Is a Target to Modulate the Expression of Receptor Mediated Endocytosis (RME) Mice Macrophages BALB/c for Optimizing the Phagocytosis toward Candida albicans

Prayitno¹,

Asnar²,

Astirin³

et al. 2013

JIBTVA

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Introduction: The existence of receptor-mediated endocytosis (RME) means that selectivity and selectivity occurs in capturing macromolecules. Protein kinase C (PKC) which can be expressed by almost all cells are proteins important in signal transduction groove that plays a role in a number of cell activity, e.g. phagocytosis. Aims: The purpose of this study is to determine the expression of RME after modulating the PKC which is characterized by the number of Candida albicans cells attached to the surface of macrophages. Methods: Peritoneal macrophages cultured BALB/c mice are treated with PMA and/or bisindolylmaleimides of providing levels of 5 ng/ml to 100 ng/ml for 10 minutes. Then immediately insert Candida albicans and observe every 30 minutes for 120 minutes. The research design used the same subject. Data collected in the form of number of Candida albicans cells attached to the surface of macrophages are analyzed with ANOVA statistical test (one way) to show the differences between treatments. Results: The test shows statistically significant difference in the number of Candida albicans cells attached to the surface of macrophages after administration of various levels of PMA (p < 0.001). The higher level of PMA is given, the more active the PKC is, the more RME are formed, the more Candida albicans cells attached to the surface of macrophages. Another result shows statistically significant difference in the number of Candida albicans cells attached to the surface of macrophages after administration of various levels of bisindolylmaleimides (p < 0.001). The higher level of bisindolylmaleimide is given, the less active PKC is, and the less RME are formed, the less Candida albicans cells attached to the surface of macrophages. Conclusion: Research shows that activator PKC (PMA) can increase the expression of RME on macrophages. Another research shows that inhibitor PKC (bisindolylmaleimides) can decrease the expression of RME on macrophages.

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“…Considering the importance of hERG as an antitarget, surprisingly few natural products have been tested for hERG channel blocking properties. A number of structurally diverse natural products have been shown to diminish hERG channel activity in vitro, e.g., naringenin, trimethyl-apigenin, curcumin, lobeline, chelerythrine, papaverine, and capsaicin [12][13][14][15][16][17][18]. It has been shown that the consumption of 1 L of freshly squeezed pink grapefruit juice (containing the hERG channel blocking flavanone naringenin) leads to a mild prolongation of the QTc interval in both young healthy volunteers and patients suffering from cardiomyopathy [12,19].…”

Section: Abbreviationsmentioning

confidence: 99%

Natural Products as Potential Human Ether-a-Go-Go-Related Gene Channel Inhibitors – Outcomes from a Screening of Widely Used Herbal Medicines and Edible Plants

et al. 2014

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Inhibition of the human ether-a-go-go-related gene channel is the single most important risk factor leading to acquired long QT syndrome. Drug-induced QT prolongation can cause severe cardiac complications, including arrhythmia, and is thus a liability in drug development. Considering the importance of the human ether-a-go-go-related gene channel as an antitarget and the daily intake of plant-derived foods and herbal products, surprisingly few natural products have been tested for channel blocking properties. In an assessment of possible human ether-a-go-go-related gene liabilities, a selection of widely used herbal medicines and edible plants (vegetables, fruits, and spices) was screened by means of a functional two-microelectrode voltage-clamp assay with Xenopus oocytes. The human ether-a-go-go-related gene channel blocking activity of selected extracts was investigated with the aid of a high-performance liquid chromatography-based profiling approach, and attributed to tannins and alkaloids. Major European medicinal plants and frequently consumed food plants were found to have a low risk for human ether-a-go-go-related gene toxicity.

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Effects of the PKC inhibitors chelerythrine and bisindolylmaleimide I (GF 109203X) on delayed rectifier K+ currents

Cited by 16 publications

References 23 publications

Protein kinase C enhances human sodium channel hNav1.7 resurgent currents via a serine residue in the domain III–IV linker

Protein kinase C enhances human sodium channel hNav1.7 resurgent currents via a serine residue in the domain III–IV linker

PKC Is a Target to Modulate the Expression of Receptor Mediated Endocytosis (RME) Mice Macrophages BALB/c for Optimizing the Phagocytosis toward Candida albicans

Natural Products as Potential Human Ether-a-Go-Go-Related Gene Channel Inhibitors – Outcomes from a Screening of Widely Used Herbal Medicines and Edible Plants

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