PuSH - Publikationsserver des Helmholtz Zentrums München: Mode of cell death induction by pharmacological Vacuolar H<sup>+</sup>-ATPase (V-ATPase) inhibition.

Informationen

Hinweise zu Qualitätskriterien von Zeitschriften

Open-Access-Richtlinie der Helmholtz-Gemeinschaft 2016

CC Licencences

Metriken für Publikationen

Navigation

Startseite

English

EVA: Veröffentlichen

Neuer EVA Antrag

Recherche

Erweiterte Suche

Durchblättern nach ...

... HMGU-Autoren/Konsortien

... Organisationsstruktur

... Zeitschriften

... Publikationstypen

... Forschungsdaten

... Arbeitsgruppen

... Erscheinungsjahr

Publikationen im Überblick

Statistik

HGF Fortschrittsbericht

OA Publikationen

Eintragen

Neue Publikation eintragen

Neue Publikation holen aus...

...EVA

Fehlende Publikation melden

Highlights

Suche

Hilfe & Kontakt

Ansprechpartner

Hilfe

Datenschutz

Helmholtz Open Science

Bibliometrische Indikatoren

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

von Schwarzenberg, K.* ; Wiedmann, R.M.* ; Oak, P.* ; Schulz, S. ; Zischka, H. ; Wanner, G.* ; Efferth, T.* ; Trauner, D.* ; Vollmar, A.M.*

Mode of cell death induction by pharmacological Vacuolar H⁺-ATPase (V-ATPase) inhibition.

J. Biol. Chem. 288, 1385-1396 (2013)

Verlagsversion Volltext

DOI

PMC

	Open Access Gold

Abstract
Metriken
Zusatzinfos

The vacuolar H(+)-ATPase (V-ATPase), a multisubunit proton pump, has come into focus as an attractive target in cancer invasion. However, little is known about the role of V-ATPase in cell death, and especially the underlying mechanisms remain mostly unknown. We used the myxobacterial macrolide archazolid B, a potent inhibitor of the V-ATPase, as an experimental drug as well as a chemical tool to decipher V-ATPase-related cell death signaling. We found that archazolid induced apoptosis in highly invasive tumor cells at nanomolar concentrations which was executed by the mitochondrial pathway. Prior to apoptosis induction archazolid led to the activation of a cellular stress response including activation of the hypoxia-inducible factor-1α (HIF1α) and autophagy. Autophagy, which was demonstrated by degradation of p62 or fusion of autophagosomes with lysosomes, was induced at low concentrations of archazolid that not yet increase pH in lysosomes. HIF1α was induced due to energy stress shown by a decline of the ATP level and followed by a shutdown of energy-consuming processes. As silencing HIF1α increases apoptosis, the cellular stress response was suggested to be a survival mechanism. We conclude that archazolid leads to energy stress which activates adaptive mechanisms like autophagy mediated by HIF1α and finally leads to apoptosis. We propose V-ATPase as a promising drugable target in cancer therapy caught up at the interplay of apoptosis, autophagy, and cellular/metabolic stress.

Impact Factor

Scopus SNIP

Web of Science
Times Cited

Scopus
Cited By

Altmetric

4.773

1.234

PuSH - Publikationsserver des Helmholtz Zentrums München

Mode of cell death induction by pharmacological Vacuolar H+-ATPase (V-ATPase) inhibition.

Mode of cell death induction by pharmacological Vacuolar H⁺-ATPase (V-ATPase) inhibition.