Acacetin causes a frequency- and use-dependent blockade of hKv1.5 channels by binding to the S6 domain

Wang, Hui; Wu, Wei; Sun, Hai Ying; Qin, Genggeng; Wang, Hong Bing; Wang, Panwen; Yalamanchili, Hari Krishna; Wang, Junwen; Tse, Hung Fat; Lau, Chu Pak; Vanhoutte, Paul M.; Li, Gui Rong

doi:10.1016/j.yjmcc.2011.08.022

Cited by 42 publications

(57 citation statements)

References 36 publications

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“…It has been reported that acacetin induces cell death in human T cell leukemia Jurkat cells (23) and human breast cancer MCF-7 cells (24), presumably due to its cytotoxicity. The IC 50 value obtained by post-ES viability assay in IFM/Q3+Kir+Kv1.5 (7.6 mM) was comparable to that previously determined by electrophysiological methods (3.5 mM) (18) and that obtained in the present study by measurement of current inhibition at the pulse end (4.7 mM) ( Table 1). Since cell death by acacetin was not observed without ES in IFM/ Q3+Kir+Kv1.5, the cell death upon ES was due to the blockade of the Kv1.5 channel.…”

Section: Discussionsupporting

confidence: 90%

“…Effects of acacetin and citalopram on Kv1.5 channels currents have been reported based on electrophysiological results in a heterologous expression system (17,18). However, the effects were also determined in this study using HEK293 cells heterologously expressing Kv1.5 alone under the same experimental conditions for Kv1.3 channel current measurements in Fig.…”

Section: Effects Of Acacetin and Citalopram On Membrane Currents Thromentioning

confidence: 86%

“…It has been reported that acacetin and citalopram possess inhibitory actions on the Kv1.5 channel (17,18). However, it remains to be determined whether these compounds also affect the Kv1.3 channel or not.…”

Section: Effects Of Acacetin and Citalopram On The Post-es Viability mentioning

confidence: 99%

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New Screening System for Selective Blockers of Voltage-Gated K+ Channels Using Recombinant Cell Lines Dying Upon Single Action Potential

et al. 2013

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Abstract. To develop a simple screening system for blockers of voltage-gated Kv1.3 and Kv1.5 channels, new cell lines co-expressing mutated Nav1.5 (IFM/Q3), K ir 2.1 (Kir), and Kv1.3 or Kv1.5 were introduced as IFM/Q3+Kir+Kv1.3 and IFM/Q3+Kir+Kv1.5, respectively. Electrical stimulation (ES) of a cell line, IFM/Q3+Kir, induced prolonged action potentials due to the slow inactivation of IFM/Q3 and subsequent cell death. Additional co-expression of Kv1.3 or Kv1.5 to IFM/Q3+Kir shortened the evoked action potentials and prevented cell death. In the presence of margatoxin, a selective Kv1.3-blocker, ES induced cell death in IFM/Q3+Kir+Kv1.3, but not in IFM/Q3+Kir+Kv1.5. In the presence of 4-aminopyridine, a non-selective Kv-channel blocker, ES application elicited cell death in both cell lines. The IC 50 s of acacetin, a Kv1.5-blocker, was 10.2 mM in IFM/Q3+Kir+Kv1.3 and almost identical to that in IFM/Q3+Kir+Kv1.5 (7.6 mM). The IC 50 s of citalopram, a 5-HT uptake-inhibitor, were 1.8 mM in IFM/Q3+Kir+Kv1.3 and 1.5 mM in IFM/Q3+Kir+Kv1.5, respectively. These IC 50 s were comparable to those determined electrophysiologically. In conclusion, acacetin and citalopram block both Kv1.3 and Kv1.5 without selectivity. The Kv1.3 or Kv1.5 channel inhibition assay using these new cell lines may be applicable to high-throughput screening because of its simplicity, accuracy, and high costperformance.

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Section: Discussionsupporting

confidence: 90%

Section: Effects Of Acacetin and Citalopram On Membrane Currents Thromentioning

confidence: 86%

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New Screening System for Selective Blockers of Voltage-Gated K+ Channels Using Recombinant Cell Lines Dying Upon Single Action Potential

et al. 2013

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“…The atrial and ventricular fast Na+ currents (INa) show different properties in the voltagedependent inactivation of the channel, mediating the possibility for atrial-selective sodium channel block [2]. The ultra-rapid delayed rectifier potassium current (IKur) carried by Kv1.5 channel contributes to repolarization in the atria but not in the ventricles [3,4]. Recent studies suggest that the atrial-selective blockade of IKur is a potentially effective strategy for the pharmacological treatment of AF [5].…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies suggest that the atrial-selective blockade of IKur is a potentially effective strategy for the pharmacological treatment of AF [5]. Among the selective IKur blockers, Acacetin, a natural flavone initially isolated from a traditional Chinese medicine Xuelianhua, was demonstrated to be a promising atrial-selective agent for the treatment of AF [3,5].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Anti:arrhythmic Effects of Combined Blockade of Sodium and Ultra:rapid Delayed Rectifier Potassium Channels in Human Atria

Whittaker

Wang

et al. 2016

2016 Computing in Cardiology Conference (CinC)

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Constructing E. coli Co‐Cultures for De Novo Biosynthesis of Natural Product Acacetin

Wang

Shao

et al. 2020

Biotechnology Journal

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Modular co‐culture engineering is an emerging approach for biosynthesis of complex natural products. In this study, microbial co‐cultures composed of two and three Escherichia coli strains, respectively, are constructed for de novo biosynthesis of flavonoid acacetin, a value‐added natural compound possessing numerous demonstrated biological activities, from simple carbon substrate glucose. To this end, the heterologous biosynthetic pathway is divided into different modules, each of which is accommodated in a dedicated E. coli strain for functional expression. After the optimization of the inoculation ratio between the constituent strains, the engineered co‐cultures show a 4.83‐fold improvement in production comparing to the mono‐culture controls. Importantly, cultivation of the three‐strain co‐culture in shake flasks result in the production of 20.3 mg L−1 acacetin after 48 h. To the authors' knowledge, this is the first report on acacetin de novo biosynthesis in a heterologous microbial host. The results of this work confirm the effectiveness of modular co‐culture engineering for complex flavonoid biosynthesis.

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Acacetin causes a frequency- and use-dependent blockade of hKv1.5 channels by binding to the S6 domain

Cited by 42 publications

References 36 publications

New Screening System for Selective Blockers of Voltage-Gated K+ Channels Using Recombinant Cell Lines Dying Upon Single Action Potential

New Screening System for Selective Blockers of Voltage-Gated K+ Channels Using Recombinant Cell Lines Dying Upon Single Action Potential

Synergistic Anti:arrhythmic Effects of Combined Blockade of Sodium and Ultra:rapid Delayed Rectifier Potassium Channels in Human Atria

Constructing E. coli Co‐Cultures for De Novo Biosynthesis of Natural Product Acacetin

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