Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-32555

Dumitru, C A; Sandalcioglu, I E; Wagner, M; Weller, M; Gulbins, E (2009). Lysosomal ceramide mediates gemcitabine-induced death of glioma cells. Journal of Molecular Medicine, 87(11):1123-1132.

[img]
Preview
Accepted Version
PDF
1MB

View at publisher
[img] PDF - Registered users only
296kB

Abstract

Acid sphingomyelinase-induced ceramide release has been shown by many studies to induce apoptosis in response to various stimuli. However, the mechanisms of acid sphingomyelinase/ceramide-mediated death signaling following treatment with chemotherapeutic drugs have not been fully elucidated thus far. The present study demonstrates that treatment of glioma cells with clinically achievable doses of gemcitabine results in acid sphingomyelinase activation, lysosomal accumulation of ceramide, cathepsin D activation, Bax insertion into the mitochondria, and cell death. Pharmacological inhibition or genetic deficiency of acid sphingomyelinase prevented these events while overexpression of the enzyme sensitized cells to gemcitabine. Likewise, inhibitors of lysosomal functions also prevent gemcitabine-induced cell death. Our data indicate a critical role of the acid sphingomyelinase/ceramide system for gemcitabine-induced signaling and suggest that lysosomal ceramide accumulation mediates cell death induced by a chemotherapeutic drug.

Citations

15 citations in Web of Science®
18 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

0 downloads since deposited on 01 Mar 2010
5 downloads since 12 months

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
DDC:610 Medicine & health
Language:English
Date:2009
Deposited On:01 Mar 2010 07:59
Last Modified:17 Jul 2014 05:08
Publisher:Springer
ISSN:0946-2716
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:10.1007/s00109-009-0514-8
PubMed ID:19763526

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page