tokyo medical and dental university, tokyo, japan, 2000-2005

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

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

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

Page 2: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 3: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Both panaxadiols and panaxatriols activate IKs.

Page 4: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

NO produced by eNOS, but not nNOS, is responsible for IKsenhancement by ginsenoside Re.

Page 5: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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 IKsenhancement.

Page 6: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 7: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Involvement of sex hormone receptors on IKs enhancement by ginsenosides

Page 8: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of ginsenoside Re on Akt phosphorylation

Page 9: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 10: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of ginsenosides on proliferation of MCF-7 and LNCaP

Page 11: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of ginsenoside on recruitmentof coactivator examined by

FRET experiments

Page 12: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 13: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of testosterone on APD

Page 14: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of testosterone on membrane currents

Page 15: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Dose-dependence of ICa,L suppression and IKsenhancement by testosterone

Page 16: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of nisoldipine and chromanol 293B on APD shortening

Page 17: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 18: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of inhibitors of the signal molecules in thenongenomic pathway of testosterone

Page 19: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Phosphorylation of Akt and NOS3 bytestosterone

Page 20: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of testosterone on isolated Langendorff-perfused hearts

Page 21: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Proposed schematic model for regulatory mechanismof testosterone on ICa,L and IKs

Page 22: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Role of Nitric Oxide in Ca2 Sensitivity of the SlowlyActivating 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

Page 23: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 24: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Effects of IKs blocker and ICa,L blocker onA23187-induced APD shortening

Page 25: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 26: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 27: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 28: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 29: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

The University of Oklahoma Health Sciences Center2005-2009

Page 30: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Activation of TRPP2 through mDia1-dependent voltage gating

Chang-Xi Bai1, Sehyun Kim1, Wei-PingLi1,3, Andrew J Streets2, Albert CM Ong2

and Leonidas Tsiokas1,*

Department of Cell Biology, University of Oklahoma Health SciencesCenter, 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

Page 31: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 32: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 33: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Voltage-dependent block of TRPP2 by activated mDia1

Page 34: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Structure–function analysis of mDia1

Page 35: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 36: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Activation of TRPP2 by EGF through mDia1-dependent gating

Page 37: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Proposed scheme of the mDia1-dependent regulation of TRPP2

Page 38: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

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

Page 39: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005
Page 40: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005

Figure 5. Co-localization of TRPP2 and TRPC1 in primary cilium and association in rat kidney membranes(A) LLC-PK1 cells were stained with a monoclonal antibody to acetylated a-tubulin (611B) (red) or rabbit polyclonal antibody to TRPC1 (green). mIMCD3 cells were stained with a mouse polyclonal antibody to TRPC1 (1F1) (red) or rabbit polyclonal antibody to TRPP2 (green). ( B) Mouse pre-immune serum (lane 2) or mouse polyclonal a-TRPC1

(lane 3) was used to immunoprecipitate endogenous TRPC1. Lane 1: 100 µg kidney membrane lysates were immunoblotted with chick en a-TRPP2.

199

1 2 3

TRPP2

lysate

s (

inp

ut)

Pre

-im

mu

ne

a-T

RP

C1

A B

a-tubulin TRPC1 merge

TRPC1 TRPP2 merge

LL

C-P

K1

mIM

CD

3

128

85

Page 41: Tokyo Medical and Dental University, Tokyo, Japan, 2000-2005