HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, Y. Articles by Simon, S. M. Search for Related Content PubMed PubMed Citation Articles by Chen, Y. Articles by Simon, S. M. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 26, 18364-18373, June 25, 1999

A Mechanism for Tamoxifen-mediated Inhibition of Acidification

Yu Chen, Melvin Schindler^¶, and Sanford M. Simon

From the  Laboratory of Cellular Biophysics, Rockefeller University, New York, New York 10021 and the ^¶ Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824

Tamoxifen has been reported to inhibit acidification of cytoplasmic organelles in mammalian cells. Here, the mechanism of this inhibition is investigated using in vitro assays on isolated organelles and liposomes. Tamoxifen inhibited ATP-dependent acidification in organelles from a variety of sources, including isolated microsomes from mammalian cells, vacuoles from Saccharomyces cerevisiae, and inverted membrane vesicles from Escherichia coli. Tamoxifen increased the ATPase activity of the vacuolar proton ATPase but decreased the membrane potential (V_m) generated by this proton pump, suggesting that tamoxifen may act by increasing proton permeability. In liposomes, tamoxifen increased the rate of pH dissipation. Studies comparing the effect of tamoxifen on pH gradients using different salt conditions and with other known ionophores suggest that tamoxifen affects transmembrane pH through two independent mechanisms. First, as a lipophilic weak base, it partitions into acidic vesicles, resulting in rapid neutralization. Second, it mediates coupled, electroneutral transport of proton or hydroxide with chloride. An understanding of the biochemical mechanism(s) for the effects of tamoxifen that are independent of the estrogen receptor could contribute to predicting side effects of tamoxifen and in designing screens to select for estrogen-receptor antagonists without these side effects.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				H. Devalapally, Z. Duan, M. V. Seiden, and M. M. Amiji Modulation of Drug Resistance in Ovarian Adenocarcinoma by Enhancing Intracellular Ceramide Using Tamoxifen-Loaded Biodegradable Polymeric Nanoparticles Clin. Cancer Res., May 15, 2008; 14(10): 3193 - 3203. [Abstract] [Full Text] [PDF]

				J. Liu, W. Lu, D. Reigada, J. Nguyen, A. M. Laties, and C. H. Mitchell Restoration of Lysosomal pH in RPE Cells from Cultured Human and ABCA4-/- Mice: Pharmacologic Approaches and Functional Recovery Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 772 - 780. [Abstract] [Full Text] [PDF]

				D. C. Miguel, J. K. U. Yokoyama-Yasunaka, W. K. Andreoli, R. A. Mortara, and S. R. B. Uliana Tamoxifen is effective against Leishmania and induces a rapid alkalinization of parasitophorous vacuoles harbouring Leishmania (Leishmania) amazonensis amastigotes J. Antimicrob. Chemother., September 1, 2007; 60(3): 526 - 534. [Abstract] [Full Text] [PDF]

				G. I. Gorodeski, U. Hopfer, C. C. Liu, and E. Margles Estrogen Acidifies Vaginal pH by Up-Regulation of Proton Secretion via the Apical Membrane of Vaginal-Ectocervical Epithelial Cells Endocrinology, February 1, 2005; 146(2): 816 - 824. [Abstract] [Full Text] [PDF]

				V. Paharkova-Vatchkova, R. Maldonado, and S. Kovats Estrogen Preferentially Promotes the Differentiation of CD11c+ CD11bintermediate Dendritic Cells from Bone Marrow Precursors J. Immunol., February 1, 2004; 172(3): 1426 - 1436. [Abstract] [Full Text] [PDF]

				A. Rajagopal and S. M. Simon Subcellular Localization and Activity of Multidrug Resistance Proteins Mol. Biol. Cell, August 1, 2003; 14(8): 3389 - 3399. [Abstract] [Full Text] [PDF]

				A. Rajagopal, A. C. Pant, S. M. Simon, and Y. Chen In Vivo Analysis of Human Multidrug Resistance Protein 1 (MRP1) Activity Using Transient Expression of Fluorescently Tagged MRP1 Cancer Res., January 1, 2002; 62(2): 391 - 396. [Abstract] [Full Text] [PDF]

				C. H Mitchell, K. Peterson-Yantorno, M. Coca-Prados, and M. M Civan Tamoxifen and ATP synergistically activate Cl- release by cultured bovine pigmented ciliary epithelial cells J. Physiol., May 15, 2000; 525(1): 183 - 193. [Abstract] [Full Text] [PDF]

				M. Braun and F. Thévenod Photoaffinity Labeling and Purification of ZG-16p, a High-Affinity Dihydropyridine Binding Protein of Rat Pancreatic Zymogen Granule Membranes that Regulates a K+-Selective Conductance Mol. Pharmacol., February 1, 2000; 57(2): 308 - 316. [Abstract] [Full Text]