Inhibition of vacuolar ATPase attenuates the TRAIL-induced activation of caspase-8 and modulates the trafficking of TRAIL receptosomes
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
23678861
DOI
10.1111/febs.12347
Knihovny.cz E-resources
- Keywords
- TRAIL, V-ATPase, acidification, apoptosis, caspase-8,
- MeSH
- Enzyme Activation MeSH
- Apoptosis MeSH
- Down-Regulation MeSH
- Endosomes metabolism MeSH
- CASP8 and FADD-Like Apoptosis Regulating Protein metabolism MeSH
- Caspase 8 metabolism MeSH
- Hydrogen-Ion Concentration MeSH
- Humans MeSH
- Macrolides pharmacology MeSH
- Cell Line, Tumor MeSH
- TNF-Related Apoptosis-Inducing Ligand pharmacology MeSH
- Antineoplastic Agents pharmacology MeSH
- Sphingolipids physiology MeSH
- Sphingomyelin Phosphodiesterase metabolism MeSH
- Death Domain Receptor Signaling Adaptor Proteins metabolism MeSH
- Signal Transduction drug effects MeSH
- Receptors, TNF-Related Apoptosis-Inducing Ligand metabolism MeSH
- Protein Transport MeSH
- Vacuolar Proton-Translocating ATPases antagonists & inhibitors metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- bafilomycin A1 MeSH Browser
- CASP8 protein, human MeSH Browser
- concanamycin A MeSH Browser
- CASP8 and FADD-Like Apoptosis Regulating Protein MeSH
- Caspase 8 MeSH
- Macrolides MeSH
- TNF-Related Apoptosis-Inducing Ligand MeSH
- Antineoplastic Agents MeSH
- Sphingolipids MeSH
- Sphingomyelin Phosphodiesterase MeSH
- Death Domain Receptor Signaling Adaptor Proteins MeSH
- TNFSF10 protein, human MeSH Browser
- Receptors, TNF-Related Apoptosis-Inducing Ligand MeSH
- Vacuolar Proton-Translocating ATPases MeSH
Tumour necrosis factor (TNF) related apoptosis inducing ligand (TRAIL), a membrane-bound ligand from the TNF family, has attracted significant attention due to its rather specific and effective ability to induce apoptotic death in various types of cancer cells via binding to and activating its pro-apoptotic death receptors. However, a significant number of primary cancer cells often develop resistance to TRAIL treatment, and the signalling platform behind this phenomenon is not fully understood. Upon blocking endosomal acidification by the vacuolar ATPase (V-ATPase) inhibitors bafilomycin A1 (BafA1) or concanamycin A, we observed a significantly reduced initial sensitivity of several, mainly colorectal, tumour cell lines to TRAIL-induced apoptosis. In cells pretreated with these inhibitors, the TRAIL-induced processing of caspase-8 and the aggregation and trafficking of the TRAIL receptor complexes were temporarily attenuated. Nuclear factor κB or mitogen activated protein/stress kinase signalling from the activated TRAIL receptors remained unchanged, and neither possible lysosomal permeabilization nor acid sphingomyelinase was involved in this process. The cell surface expression of TRAIL receptors and their TRAIL-induced internalization were not affected by V-ATPase inhibitors. The inhibitory effect of BafA1, however, was blunted by knockdown of the caspase-8 inhibitor cFLIP. Altogether, the data obtained provide the first evidence that endosomal acidification could represent an important regulatory node in the proximal part of TRAIL-induced pro-apoptotic signalling.
References provided by Crossref.org
Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin
Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL
