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Conventional protein kinase C isoenzymes undergo dephosphorylation in neutrophil-like HL-60 cells treated by chelerythrine or sanguinarine
J. Vrba, Z. Dvořák, J. Ulrichová, M Modrianský
Jazyk angličtina Země Nizozemsko
Typ dokumentu práce podpořená grantem
E-zdroje NLK
ProQuest Central od 1997-01-01 do Před 1 rokemMedline Complete (EBSCOhost) od 2000-02-01 do Před 1 rokem
Nursing & Allied Health Database (ProQuest) od 1997-01-01 do Před 1 rokem
Health & Medicine (ProQuest) od 1997-01-01 do Před 1 rokem
Public Health Database (ProQuest) od 1997-01-01 do Před 1 rokem
- MeSH
- alkaloidy farmakologie chemie MeSH
- benzofenantridiny farmakologie chemie MeSH
- bezbuněčný systém MeSH
- buněčná smrt účinky léků MeSH
- fosforylace účinky léků MeSH
- HL-60 buňky MeSH
- isochinoliny farmakologie chemie MeSH
- izoenzymy metabolismus MeSH
- lidé MeSH
- NADPH-oxidasy metabolismus MeSH
- neutrofily cytologie enzymologie účinky léků MeSH
- protein-serin-threoninkinasy metabolismus MeSH
- proteinkinasa C metabolismus 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
- práce podpořená grantem MeSH
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.
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- $a Conventional protein kinase C isoenzymes undergo dephosphorylation in neutrophil-like HL-60 cells treated by chelerythrine or sanguinarine / $c J. Vrba, Z. Dvořák, J. Ulrichová, M Modrianský
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- $a Department of Medical Chemistry and Biochemistry, Faculty of Medicine, Palacky University, Olomouc, Czech Republic. vrbambv@seznam.cz
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- $a 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.
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