Inhibitory modulation of ATP-sensitive potassium channels by gallate-ester moiety of (-)-epigallocatechin-3-gallate

Authors
Won-Ki BaekByeong-Churl JangJun Hee LimTaeg-Kyu KwonHyun-Young LeeChi-Heum ChoDae-Kwang KimDong-Hoon ShinJong-Gu ParkJeong-Geun LimJi-Hyun BaeJae-Hoon BaeSun Kyun YooWon-Kyun ParkDae-Kyu Song
Department
Dept. of Physiology (생리학); Dept. of Microbiology (미생물학); Dept. of Molecular Medicine (분자의학); Dept. of Immunology (면역학); Dept. of Neurology (신경과학); Dept. of Preventive Medicine (예방의학); Dept. of Obstetrics & Gynecology (산부인과학); Dept. of Medical Education (의학교육학); Dept. of Medical Genetics(의학유전학)
Issue Date
2005
Citation
Biochemical Pharmacology, Vol.70(11) : 1560-1567, 2005
ISSN
0006-2952
Abstract
(−)-Epigallocatechin-3-gallate (EGCG), a major polyphenolic substance found in green tea, is well recognized to be beneficial for human health. However, it is still controversial as to what dose of this compound is indeed good for human health. Though some recent studies have interestingly reported various beneficial effects of EGCG in cell culture system, however, plasma levels of EGCG attainable by oral regular intake in humans are normally in nanomolar range. However, potential side effects of EGCG when administered parenterally at higher concentration have not been thoroughly tested. Here, we evaluated the effect of EGCG on ATP-sensitive potassium (KATP) channels expressed in Xenopus oocytes. EGCG inhibited the activity of the Kir6.2/SUR1 and Kir6.2ΔC36 channels with IC50 of 142 ± 37 and 19.9 ± 1.7 μM, respectively. Inhibition of EGCG was also observed in Kir6.2/SUR2A or Kir6.2/SUR2B channels. Notably, (−)-epicatechin-3-gallate (ECG), another major polyphenolic substance in green tea, was found to reduce the channel activity with greater potency than EGCG. In contrast to EGCG and ECG, which have the gallic acid-ester moiety in their own structures, (−)-epigallocatechin and (−)-epicatechin exhibited very weak inhibition of the KATP channel. Collectively, these results suggest that the gallate-ester moiety of epicatechins may be critical for inhibiting the KATP channel activity via the pore-forming subunit Kir6.2 and this may be a possible mechanism by which green tea extracts or EGCG may cause unexpected side effects at micromolar plasma level. Keywords EGCG; ATP-sensitive potassium channel; Gallate-ester moiety; Kir6.2; Xenopus oocyte; Pancreatic β-cell
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35150
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Neurology (신경과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Obstetrics & Gynecology (산부인과학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Medical Education (의학교육학)
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Medical Genetics (의학유전학)
Keimyung Author(s)
배재훈; 송대규; 백원기; 장병철; 박종구; 권택규; 임정근; 신동훈; 조치흠; 김대광; 박원균
Full Text
https://www.sciencedirect.com/science/article/pii/S0006295205005952?via%3Dihub
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