• Title/Summary/Keyword: ERG

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Acepromazine inhibits hERG potassium ion channels expressed in human embryonic kidney 293 cells

  • Joo, Young Shin;Lee, Hong Joon;Choi, Jin-Sung;Sung, Ki-Wug
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.1
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    • pp.75-82
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    • 2017
  • The effects of acepromazine on human ether-$\grave{a}$-go-go-related gene (hERG) potassium channels were investigated using whole-cell voltage-clamp technique in human embryonic kidney (HEK293) cells transfected with hERG. The hERG currents were recorded with or without acepromazine, and the steady-state and peak tail currents were analyzed for the evaluating the drug effects. Acepromazine inhibited the hERG currents in a concentration-dependent manner with an $IC_{50}$ value of $1.5{\mu}M$ and Hill coefficient of 1.1. Acepromazine blocked hERG currents in a voltage-dependent manner between -40 and +10 mV. Before and after application of acepromazine, the half activation potentials of hERG currents changed to hyperpolarizing direction. Acepromazine blocked both the steady-state hERG currents by depolarizing pulse and the peak tail currents by repolarizing pulse; however, the extent of blocking by acepromazine in the repolarizing pulse was more profound than that in the depolarizing pulse, indicating that acepromazine has a high affinity for the open state of the channels, with a relatively lower affinity for the closed state of hERG channels. A fast application of acepromazine during the tail currents inhibited the open state of hERG channels in a concentration-dependent. The steady-state inactivation of hERG currents shifted to the hyperpolarized direction by acepromazine. These results suggest that acepromazine inhibits the hERG channels probably by an open- and inactivated-channel blocking mechanism. Regarding to the fact that the hERG channels are the potential target of drug-induced long QT syndrome, our results suggest that acepromazine can possibly induce a cardiac arrhythmia through the inhibition of hERG channels.

The Effects of ERG Factors on Organizational Attachment: Focused on the Mediating Effects of Self-Efficacy (ERG요인이 조직애착에 미치는 영향: 자기효능감의 매개효과를 중심으로)

  • Jang, Jun-ho;Jin, Chunhua
    • Journal of Digital Convergence
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    • v.19 no.3
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    • pp.109-114
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    • 2021
  • This study is to verify the mediating effect of self-efficacy in the relationship between elements of the ERG and organizational attachment. To verify this, a survey was conducted on employees working at companies in Korea and the research found that all three elements of ERG have a significant effect on self-efficacy, and self-efficacy also have a significant effect on organizational attachment. Thus, it was found that self-efficacy played a mediating role in the relationship between the three elements of ERG and organizational attachment. Based on these findings, we present practical implications while also presenting future research directions.

The Impacts of ERG Factors on Organization-based Self-esteem: Focusing on the Mediating Effects Resilience (ERG요인이 조직기반자긍심에 미치는 영향: 회복탄력성의 매개효과를 중심으로)

  • Jang, Jun-ho;Nam, Sang-Mu
    • Journal of Digital Convergence
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    • v.20 no.5
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    • pp.331-336
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    • 2022
  • This study proved that the importance of Alderfer's ERG theory. it checked the effects of these three elements on organization-based self-esteem through resilience. In particular, the relationship between the ERG and the psychological factors of the members of the organization is investigated. Moreover, we attempt to verify the mediating effect of resilience on the relationship between ERG and organization-based self-esteem. This study was used for analysis a survey on data 265 employees in 10 organizations. The major finding are as follows. it was found that all three elements of ERG was positively effected resilience. Furthermore, resilience was found to improve the level of organization-based self-esteem. Finally, it was found that resilience have played a mediating role on the relationship between the ERG and organization-based self-esteem. In the conclusion, the summary and implications of the study and the future direction of the study were presented.

hERG Channel-Related Cardiotoxicity Assessment of 13 Herbal Medicines (한약재 13종의 hERG 채널 관련 심장독성 평가)

  • Ha, Hyekyung;Lee, Sion;Kim, Dong-Hyun;Seo, Chang-Seob;Shin, Hyeun-kyoo
    • The Journal of Korean Medicine
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    • v.42 no.3
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    • pp.44-55
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    • 2021
  • Objectives: As the use of herbal medicinal products (HMPs) increases worldwide, systematic verification of the safety of HMPs is required. The induction of cardiotoxicity is one of the major factors in post-approval withdrawal of medicinal products, and drug-induced cardiotoxicity assessment is emerging as an important step in drug development. In the present study, we evaluated human ether-à-go-go-related gene (hERG) potassium channel-related cardiotoxicity to predict the risk of cardiac arrhythmia in thirteen herbal medicines known to have cardiac toxicity. Methods: We measured the inhibition rate of hERG potassium channel activity of 13 medicinal herbal extracts in hERG-expressing HEK 293 cells using an automated patch-clamping system. Quinidine was used as a positive control for inhibition of hERG activity. Results: Extracts of Evodiae Fructus, Strychni Semen, and Corydalis Tuber potently inhibited the activity of hERG, and IC50 values were 3.158, 19.87, and 41.26 ㎍/mL, respectively. Cnidi Fructus, Ephedra Herba, Lithospermi Radix, Polygoni Multiflori Radix, Visci Ramulus et Folium, Asiasari Radix et Rhizoma, and Scolopendra weakly inhibited hERG activity, and the IC50 value for each herbal medicine was more than 400 ㎍/mL. Aconiti Kusnezoffii Tuber and two types of Aconiti Lateralis Radix Preparata (Po and Yeom) had weak inhibitory activity against hERG, and the IC50 values were more than 700 ㎍/mL. The IC50 value of quinidine against hERG was 1.021 𝜇M. Conclusion: Evodiae Fructus, Strychni Semen, and Corydalis Tuber acted as potent inhibitors against hERG. These herbal medicines may cause cardiac arrhythmia through QT prolongation, so care should be taken when taking them.

The Impacts of ERG Factors on Organizational Attachment: Focused on the Mediating Effects Job Fit (ERG요인이 조직애착에 미치는 영향: 직무적합성의 매개효과를 중심으로)

  • Jang, Jun-ho;Qing, Cheng-lin;Jin, Xiu
    • Journal of Digital Convergence
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    • v.19 no.1
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    • pp.23-28
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    • 2021
  • This research emphasized that the importance of ERG elements such as existence needs, relatedness needs, and growth needs. Moreover, it focused on verifying the effects of these three elements on organizational attachment through person job fit. In addition, the mediating role of person job fit was clearly identified as a key variable that can lead to organizational attachment. To verify this, an empirical analysis was conducted on workers engaged in state-owned company, service, manufacturing, and distribution industries in Korea. Through empirical analysis, it was found that all three elements of ERG improve person job fit. Furthermore, person job fit was found to increase the level of organizational attachment. Thus, it was found that person job fit played a partial mediating role in the relationship between the three elements of ERG and organizational attachment. This research also identified which element has the strongest influence on person job fit. Through these results, practical implications were presented and future research directions were discussed.

Cardiotoxicity assessment of 31 herbal formulae by activity of hERG potassium channel in HEK 293 cells (hERG 칼륨채널 활성도 변화에 따른 31종 한약처방의 심장독성 평가)

  • Ha, Hyekyung;Jin, Seong Eun;Lee, Sion;Kim, Dong-Hyun;Seo, Chang-Seob;Shin, Hyeun-kyoo
    • The Journal of Korean Medicine
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    • v.43 no.1
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    • pp.33-41
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    • 2022
  • Objectives: Drug-induced blockade of the human ether-à-go-go related gene (hERG) potassium ion channel causes acquired long QT syndrome, which is known to cause cardiac arrhythmias and be fatal. To establish safety evidence of herbal formulae, we evaluated the effects of 31 herbal formulae on hERG channel activity. Methods: The current through hERG channel was measured by changing the membrane voltage before and after treatment with 31 herbal formulae in HEK 293 cell overexpressing hERG channel using a whole-cell patch clamp system. The current-voltage curves and the activity curves were fitted, and the hERG activity and 50% inhibitory concentration (IC50) according to each herbal formula were calculated. Results: Chokyungjongok-tang, Oncheong-eum, and Cheongsangbangpung-tang strongly inhibited the hERG activity, with IC50 values of 67.67, 141.2, and 296.3 ㎍/mL, respectively. Yeonkyopaedok-san, Eunkyo-san, Ukgan-san gajinphibanha, Daegunjoong-tang (except Oryzae gluten), Insamyangyoung-tang, Banhahubak-tang, SokyungHwalhyul-tang, Jodeung-san, Hyeonggaeyeongyo-tang, and Bangkeehwangkee-tang weakly inhibited hERG activity, with IC50 values ranging from 400 to 1000 ㎍/mL. The other 18 herbal formulae showed very weak hERG activity inhibition of less than 50% at the highest concentration (1000 ㎍/mL). Conclusion: This study provided safety information on cardiotoxicity by cardiac arrhythmia risk assessment of herbal formulae, and is expected to be a reference data for predicting the safety and risk of herbal formulae.

Block of hERG $K^+$ Channel by Classic Histamine $H_1$ Receptor Antagonist Chlorpheniramine

  • Hong, Hee-Kyung;Jo, Su-Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.3
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    • pp.215-220
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    • 2009
  • Chlorpheniramine is a potent first-generation histamine $H_1$ receptor antagonist that can increase action potential duration and induce QT prolongation in several animal models. Since block of cardiac human ether-a-go-go-related gene (hERG) channels is one of leading causes of acquired long QT syndrome, we investigated the acute effects of chlorpheniramine on hERG channels to determine the electrophysiological basis for its proarrhythmic potential. We examined the effects of chlorpheniramine on the hERG channels expressed in Xenopus oocytes using two-microelectrode voltage-clamp techniques. Chlorpheniramine induced a concentration-dependent decrease of the current amplitude at the end of the voltage steps and hERG tail currents. The $IC_{50}$ of chlorpheniramine-dependent hERG block in Xenopus oocytes decreased progressively relative to the degree of depolarization. Chlorpheniramine affected the channels in the activated and inactivated states but not in the closed states. The S6 domain mutations Y652A and F656A partially attenuated (Y652A) or abolished (F656A) the hERG current block. These results suggest that the $H_1$ antihistamine, chlorpheniramine is a blocker of the hERG channels, providing a molecular mechanism for the drug-induced arrhythmogenic side effects.

Relation of BAALC and ERG Gene Expression with Overall Survival in Acute Myeloid Leukemia Cases

  • Rashed, Reham A;Kadry, Dalia Y;Taweel, Maha EL;Abd El Wahab, Nahed;Abd El Hameed, Thoreya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.17
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    • pp.7875-7882
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    • 2015
  • Background: The objectives of this study were to evaluate the expression of brain and acute leukemia, cytoplasmic (BAALC) gene and erythroblast transformation-specific related gene (ERG) in de novo cases of acute myeloid leukemia (AML) and identify roles in disease progression and outcome. Materials and Methods: This study included 50 newly diagnosed AML patients, along with 10 apparently healthy normal controls. BAALC and ERG expression was detected in the bone marrow of both patients and controls using real-time RT-PCR. Results: BAALC and ERG expression was detected in 52% of cases but not in any controls. There was a statistically significant correlation between BAALC and ERG gene expression and age (p-value=0.004 and 0.019, respectively). No statistical significance was noted for sex, lymphadenopathy, hepatomegaly, splenomegaly, other hematological findings, immunophenotyping and FAB sub-classification except for ERG gene and FAB (p-value=0.058). A statistical significant correlation was found between response to treatment with ERG expression (p-value=0.028) and age (p-value=0.014). A statistically significant variation in overall survival was evident with patient age, BM blast cells, FAB subgroups, BAALC and ERG expression (p-value=<0.001, 0.045, 0.041, <0.008 and 0.025 respectively). Conclusions: Our results suggest that BAALC and ERG genes are specific significant molecular markers in AML disease progression, response to treatment and survival.

ERG Signal Modeling Based on the Retinal Model

  • Chae, S.P.;Lee, J.W.;Jang, W.Y.;Kim, M.N.;Kim, S.Y.;Cho, J.H.
    • Proceedings of the IEEK Conference
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    • 2000.07b
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    • pp.637-640
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    • 2000
  • ERG signal represents the responses of the each layer of retina for the visual stimulus and accumulated responses according to the signal processing occurring in the retina. By investigating the reaction types of each wave of the ERG, various kinds of information for the diagnosis and the signal processing mechanisms in the retina can be obtained. In this paper, the ERG signal is generated by simulating of the volume conductor field of response of each retina layer and summing of them algebraically. The retina model used for simulation is Shah’s Computer Retina model which is one of the most reliable models recently developed. The generated ERG is compared with the typical ERG and shows a very close similarity. By changing the parameters of the retina model, the diagnostic investigation is performed with the variation of the ERG waveform.

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Cardiac Safety Assessment of Medicinal Herbal Formulas Using hERG-HEK 293 cell (hERG 칼륨 채널 매개성 HEK 293 세포를 이용한 한약 처방의 심장 독성 평가 연구)

  • Choi, Susanna;Kwon, Oh-Bin;Lee, SION;Seo, Chang-Seob;Shin, Hyeun-Kyoo
    • The Journal of Korean Medicine
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    • v.40 no.2
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    • pp.94-105
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    • 2019
  • Objectives: The correlation between medicinal herbal formulas and a risk of cardiotoxicity has been controversial. Thus, this study investigated cardiac safety assessment of 52 most commonly used medicinal herbal formulas. Methods: We evaluated the in vitro effects of medicinal herbal formulas on recombinant human embryonic kidney 293 (HEK 293) cell line expressing human ether-a-go-go-related gene (hERG) potassium channel. Results and Conclusion: Our results demonstrated that all of 52 medicinal herbal formulas did not show inhibition of hERG current in hERG-HEK 293 recombinant cells. In conclusion, these safety data suggest that 52 medicinal herbal formulas were not associated with an increased risk of cardiotoxicity in hERG-HEK 293 recombinant cells.