modeofcelldeathinductionbypharmacologicalvacuolar stronghstrong -atpase(v.pdfVIP

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 288, NO. 2, pp. 1385–1396, January 11, 2013 © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A. Mode of Cell Death Induction by Pharmacological Vacuolar □ H -ATPase (V-ATPase) Inhibition* S Received for publication, August 20, 2012, and in revised form, November 11, 2012 Published, JBC Papers in Press, November 20, 2012, DOI 10.1074/jbc.M112.412007 ‡1 ‡ § ¶ ¶ Karin von Schwarzenberg , Romina M. Wiedmann , Prajakta Oak , Sabine Schulz , Hans Zischka , Gerhard Wanner, Thomas Efferth**, Dirk Trauner‡‡, and Angelika M. Vollmar‡ From the ‡Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University, 81377 Munich, Germany, the §Department of Pharmacy, Pharmaceutical Biology-Biotechnology, Ludwig-Maximilians-University, 81377 Munich, Germany, the ¶Institute of Toxicology, Helmholtz Center Munich, German Research Center for Environmental Health, 80539 Neuherberg, Germany, the Department of Biology I, Ludwig-Maximilians-University, 81377 Munich, Germany, the **Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, 55099 Mainz, Germany, and the ‡‡Department of Chemistry, Ludwig-Maximilians-University, 81377 Munich, Germany Background: V-ATPase is proposed as tumor target, but information on cell death-inducing mechanisms is rare. Results: Cell death induced by the V-ATPase inhibitor archazolid involves the cellular stress response. Conclusion: Archazolid is a chemical tool to decipher V-ATPase-