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Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005.

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Presentation on theme: "Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005."— Presentation transcript:

1 Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

2 Ginsenoside Re, a Main Phytosterol of Panax ginseng, Activates Cardiac Potassium Channels via a Nongenomic Pathway of Sex Hormones Chang-Xi Bai, Asami Kaihara, Eri Ozaki, Takashi Kawano, Yutaka Nakaya, Muhammad Awais, Moritoshi Sato, Yoshio Umezawa, and Junko Kurokawa Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University MOLECULAR PHARMACOLOGY Vol. 70, No. 6 Copyright © 2006 The American Society for Pharmacology and Experimental Therapeutics 28134/3156556 Mol Pharmacol 70:1916–1924, 2006

3 Both panaxadiols and panaxatriols activate IKs.

4 NO produced by eNOS, but not nNOS, is responsible for IKs enhancement by ginsenoside Re.

5 Signaling cascade of IKs enhancement by ginsenoside Re. A–C, effects of SH-6 (A), an Akt inhibitor, PP2 (B), a c-Src inhibitor, and wortmannin (C), a PI-3 kinase inhibitor, on ginsenoside Re-induced IKs enhancement.

6 Effects of preincubation with various blockers on ginsenoside Re (3 M)-induced IKs enhancement

7 Involvement of sex hormone receptors on IKs enhancement by ginsenosides

8 Effects of ginsenoside Re on Akt phosphorylation

9 Ginsenoside Re binds to the human AR, ER, and PR

10 Effects of ginsenosides on proliferation of MCF-7 and LNCaP

11 Effects of ginsenoside on recruitment of coactivator examined by FRET experiments

12 Nontranscriptional Regulation of Cardiac Repolarization Currents by Testosterone Chang-Xi Bai, MD, PhD; Junko Kurokawa, PhD; Masaji Tamagawa, BE; Haruaki Nakaya, MD, PhD; Tetsushi Furukawa, MD, PhD Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University

13 Effects of testosterone on APD

14 Effects of testosterone on membrane currents

15 Dose-dependence of ICa,L suppression and IKs enhancement by testosterone

16 Effects of nisoldipine and chromanol 293B on APD shortening

17 Role of NO in testosterone-induced APD shortening, ICa,L suppression, and IKs enhancement

18 Effects of inhibitors of the signal molecules in the nongenomic pathway of testosterone

19 Phosphorylation of Akt and NOS3 by testosterone

20 Effects of testosterone on isolated Langendorff-perfused hearts

21 Proposed schematic model for regulatory mechanism of testosterone on ICa,L and IKs

22 Role of Nitric Oxide in Ca2 Sensitivity of the Slowly Activating Delayed Rectifier K Current in Cardiac Myocytes Chang-Xi Bai, Iyuki Namekata, Junko Kurokawa, Hikaru Tanaka, Koki Shigenobu, Tetsushi Furukawa Department of Bio-informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University

23 Effects of A23187 on [Ca2]i, APD, and IKs

24 Effects of IKs blocker and ICa,L blocker on A23187-induced APD shortening

25 NO and NOS3 play a role in the A23187-induced APD shortening and IKs enhancement

26 CaM, but not Akt, is involved in A23187-induced IKs enhancement and APD shortening

27 Effects of A23187 on interactions of NOS3 with Cav-3 and CaM

28 Effects of digoxin and rise in [Ca2]o on [Ca2]i, APD, and IKs

29 The University of Oklahoma Health Sciences Center 2005-2009

30 Activation of TRPP2 through mDia1- dependent voltage gating Chang-Xi Bai1, Sehyun Kim1, Wei-Ping Li1,3, Andrew J Streets2, Albert CM Ong2 and Leonidas Tsiokas1,* Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA The EMBO Journal (2008) 27, 1345–1356 | & 2008 European Molecular Biology Organization | All Rights Reserved 0261-4189/08 www.embojournal.org &2008 European Molecular Biology Organization The EMBO Journal VOL 27 | NO 9 | 2008 THE EMBO JOURNAL

31 Colocalization of mDia1 and TRPP2 at the plasma membrane of LLC-PK1 cells

32 Voltage-dependent block of endogenous TRPP2 by mDia1 in LLC-PK1 cells

33 Voltage-dependent block of TRPP2 by activated mDia1

34 Structure–function analysis of mDia1

35 Voltage-dependent gating of TRPP2 by purified mDia1 in inside-out patches

36 Activation of TRPP2 by EGF through mDia1-dependent gating

37 Proposed scheme of the mDia1-dependent regulation of TRPP2

38 Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and TRPC1 subunits Chang-Xi Bai1*, Aure´lie Giamarchi 2*, Lise Rodat-Despoix 2, Franc¸oise Padilla 2, Tamyra Downs1, Leonidas Tsiokas1+ & Patrick Delmas 2+ EMBO reports scientific report

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