Inhibition of vacuolar ATPase attenuates the TRAIL-induced activation of caspase-8 and modulates the trafficking of TRAIL receptosomes
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
23678861
DOI
10.1111/febs.12347
Knihovny.cz E-zdroje
- Klíčová slova
- TRAIL, V-ATPase, acidification, apoptosis, caspase-8,
- MeSH
- aktivace enzymů MeSH
- apoptóza MeSH
- down regulace MeSH
- endozomy metabolismus MeSH
- FLIP (buněčný) metabolismus MeSH
- kaspasa 8 metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- makrolidy farmakologie MeSH
- nádorové buněčné linie MeSH
- protein TRAIL farmakologie MeSH
- protinádorové látky farmakologie MeSH
- sfingolipidy fyziologie MeSH
- sfingomyelinfosfodiesterasa metabolismus MeSH
- signální adaptorové proteiny receptorové domény smrti metabolismus MeSH
- signální transdukce účinky léků MeSH
- TRAIL receptory metabolismus MeSH
- transport proteinů MeSH
- vakuolární protonové ATPasy antagonisté a inhibitory metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- bafilomycin A1 MeSH Prohlížeč
- CASP8 protein, human MeSH Prohlížeč
- concanamycin A MeSH Prohlížeč
- FLIP (buněčný) MeSH
- kaspasa 8 MeSH
- makrolidy MeSH
- protein TRAIL MeSH
- protinádorové látky MeSH
- sfingolipidy MeSH
- sfingomyelinfosfodiesterasa MeSH
- signální adaptorové proteiny receptorové domény smrti MeSH
- TNFSF10 protein, human MeSH Prohlížeč
- TRAIL receptory MeSH
- vakuolární protonové ATPasy 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.
Citace poskytuje Crossref.org
Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin
Enzymatically active cathepsin D sensitizes breast carcinoma cells to TRAIL
