Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M109154200 on November 7, 2001

J. Biol. Chem., Vol. 277, Issue 4, 2505-2510, January 25, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/4/2505    most recent
M109154200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kimchi-Sarfaty, C.
Right arrow Articles by Rahamimoff, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kimchi-Sarfaty, C.
Right arrow Articles by Rahamimoff, H.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Transport Activity and Surface Expression of the Na+-Ca2+ Exchanger NCX1 Are Inhibited by the Immunosuppressive Agent Cyclosporin A and by the Nonimmunosuppressive Agent PSC833*

Chava Kimchi-SarfatyDagger , Judith Kasir§, Suresh V. AmbudkarDagger , and Hannah RahamimoffDagger §

From the Dagger  Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892-4255 and § Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel

Cyclosporin A (CsA) treatment of HEK 293 cells expressing the rat heart RHE-1 (NCX1.1, EMBL accession number X68191) or the rat brain RBE-2 (NCX1.5, GenBankTM accession number X68813) Na+-Ca2+ exchanger inhibited their transport activity in a concentration-dependent manner. The inhibition was detectable at 2 µM CsA, and exposure of the cells to 20 µM CsA resulted in a decrease of the Na+-dependent Ca2+ uptake to about 20% relative to that of untreated cells. Determination of the surface expression of the exchanger protein revealed a parallel concentration-dependent reduction in the amount of the immunoreactive protein. No reduction was detected in the amount of total immunoreactive exchanger protein in CsA-treated cells relative to untreated ones. Among the different drugs tested, only PSC833, an analog of cyclosporin D, mimicked the effects of CsA. Exposure of the transfected cells to the chemically related cyclosporin D and macrolide drugs (FK506 or rapamycin) had no effect on the transport activity or the surface expression of the Na+-Ca2+ exchanger. Co-expression of the human multidrug transporter P-glycoprotein (of which both drugs are modulators) with the cloned Na+-Ca2+ exchanger revealed that transport activity and surface expression of each transporter in the co-transfected system were similar to those of each transporter alone in both the presence and absence of CsA or PSC833. CsA and PSC833 inhibited the surface expression of the NCX1 protein but did not alter the surface expression of P-glycoprotein. Unlike some P-glycoprotein endoplasmic reticulum-retained mutants (Loo, T. W., and Clarke, D. M. (1997) J. Biol. Chem. 272, 709-712), CsA did not rescue RBE-2/F913right-arrowStop, an endoplasmic reticulum-retained function-competent mutant of the Na+-Ca2+ exchanger (Kasir, J., Ren, X., Furman, I., and Rahamimoff, H. (1999) J. Biol. Chem. 274, 24873-24880) and did not induce its kinesis to the surface membrane, further demonstrating molecular differences between P-glycoprotein and NCX1 mutants for interaction with CsA.

* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Biochemistry, Hebrew University-Hadassah Medical School, P. O. Box 12272, Jerusalem 91120, Israel. Tel.: 972-2-6758511; Fax: 972-2-6784010; E-mail: Hannah@cc.huji.ac.il.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
B. Elbaz, A. Alperovitch, M. M. Gottesman, C. Kimchi-Sarfaty, and H. Rahamimoff
Modulation of Na+-Ca2+ Exchanger Expression by Immunosuppressive Drugs Is Isoform-Specific
Mol. Pharmacol., April 1, 2008; 73(4): 1254 - 1263.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Sabella, E. Faszewski, L. Himic, K. M. Colpitts, J. Kaltenbach, M. M. Burger, and X. Fernandez-Busquets
Cyclosporin A Suspends Transplantation Reactions in the Marine Sponge Microciona prolifera
J. Immunol., November 1, 2007; 179(9): 5927 - 5935.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. R. Romero, A. Rivera, V. Lanca, M. D. P. Bicho, P. R. Conlin, and D. A. Ricupero
Na+/Ca2+ Exchanger Activity Modulates Connective Tissue Growth Factor mRNA Expression in Transforming Growth Factor {beta}1- and Des-Arg10-kallidin-stimulated Myofibroblasts
J. Biol. Chem., April 15, 2005; 280(15): 14378 - 14384.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement