Conventional protein kinase C isoenzymes undergo dephosphorylation in neutrophil-like HL-60 cells treated by chelerythrine or sanguinarine
Jazyk angličtina Země Švýcarsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- alkaloidy chemie farmakologie MeSH
- benzofenantridiny chemie farmakologie MeSH
- bezbuněčný systém MeSH
- buněčná smrt účinky léků MeSH
- fosforylace účinky léků MeSH
- HL-60 buňky MeSH
- isochinoliny chemie farmakologie MeSH
- izoenzymy metabolismus MeSH
- lidé MeSH
- NADPH-oxidasy metabolismus MeSH
- neutrofily cytologie účinky léků enzymologie MeSH
- protein-serin-threoninkinasy metabolismus MeSH
- proteinkinasa C metabolismus MeSH
- proteinkinasy PDK MeSH
- respirační vzplanutí účinky léků MeSH
- substrátová specifita účinky léků MeSH
- transport proteinů účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alkaloidy MeSH
- benzofenantridiny MeSH
- chelerythrine MeSH Prohlížeč
- isochinoliny MeSH
- izoenzymy MeSH
- NADPH-oxidasy MeSH
- PDPK1 protein, human MeSH Prohlížeč
- protein-serin-threoninkinasy MeSH
- proteinkinasa C MeSH
- proteinkinasy PDK MeSH
- sanguinarine MeSH Prohlížeč
The quaternary benzo[c]phenanthridine alkaloid chelerythrine is widely used as an inhibitor of protein kinase C (PKC). However, in biological systems chelerythrine interacts with an array of proteins. In this study, we examined the effects of chelerythrine and sanguinarine on conventional PKCs (cPKCs) and PKC upstream kinase, phosphoinositide-dependent protein kinase 1 (PDK1), under complete inhibition conditions of PKC-dependent oxidative burst. In neutrophil-like HL-60 cells, sanguinarine and chelerythrine inhibited N-formyl-Met-Leu-Phe, phorbol 12-myristate 13-acetate (PMA)-, and A23187-induced oxidative burst with IC(50) values not exceeding 4.6 micromol/L, but the inhibition of PMA-stimulated cPKC activity in intact cells required at least fivefold higher alkaloid concentrations. At concentrations below 10 micromol/L, sanguinarine and chelerythrine prevented phosphorylation of approximately 80 kDa protein and sequestered approximately 60 kDa phosphoprotein in cytosol. Moreover, neither sanguinarine nor chelerythrine impaired PMA-stimulated translocation of autophosphorylated PKCalpha/betaII isoenzymes, but both alkaloids induced dephosphorylation of the turn motif in PKCalpha/betaII. The dephosphorylation did not occur in unstimulated cells and it was not accompanied by PKC degradation. Furthermore, cell treatment with sanguinarine or chelerythrine resulted in phosphorylation of approximately 70 kDa protein by PDK1. We conclude that PKC-dependent cellular events are affected by chelerythrine primarily by multiple protein interactions rather than by inhibition of PKC activity.
Citace poskytuje Crossref.org
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