2009
Stixová, Lenka; Procházková, Jirina; Soucek, Karel; Hofmanová, Jirina; Kozubík, Alois
5-Lipoxygenase inhibitors potentiate 1alpha,25-dihydroxyvitamin D3-induced monocytic differentiation by activating p38 MAPK pathway. Journal Article
In: Molecular and cellular biochemistry, vol. 330, no. 1-2, pp. 229–238, 2009, ISSN: 1573-4919 0300-8177, (Place: Netherlands).
Abstract | Links | BibTeX | Tags: Arachidonate 5-Lipoxygenase/*genetics, Benzoquinones/pharmacology, Cell Differentiation/*drug effects, HL-60 Cells, Humans, Indoles/pharmacology, Lipoxygenase Inhibitors/*pharmacology, Monocytes/*cytology, p38 Mitogen-Activated Protein Kinases/*metabolism, Vitamin D/*analogs & derivatives/pharmacology
@article{stixova_5-lipoxygenase_2009,
title = {5-Lipoxygenase inhibitors potentiate 1alpha,25-dihydroxyvitamin D3-induced monocytic differentiation by activating p38 MAPK pathway.},
author = {Lenka Stixová and Jirina Procházková and Karel Soucek and Jirina Hofmanová and Alois Kozubík},
doi = {10.1007/s11010-009-0138-x},
issn = {1573-4919 0300-8177},
year = {2009},
date = {2009-10-01},
journal = {Molecular and cellular biochemistry},
volume = {330},
number = {1-2},
pages = {229–238},
abstract = {The treatment of human promyelocytic leukemia cell lines HL-60, and to some extent NB-4, with 1alpha,25-dihydroxyvitamin D(3) (VD3) induces differentiation toward the monocytic/macrophage lineage, demonstrated by the increased expression of CD11b and CD14, and the production of opsonized zymosan particles (OZP)-stimulated reactive oxygen species (ROS). Moreover, in more sensitive HL-60 cells, increased expression of 5-lipoxygenase (5-LPO), Mcl-1, IkappaB, and c-Jun, accompanied by the activation of p38 MAPK, was detected. These VD3 effects on HL-60 cell differentiation were significantly potentiated by 5-LPO inhibitors MK-886 and AA-861 and were inverted by SB202190 (SB), a p38 MAPK inhibitor. The inhibition of differentiation by SB was demonstrated by a reduction of CD14 expression and by a decrease in OZP-activated ROS production. These results indicated that p38 MAPK pathway is involved in 5-LPO inhibitors-dependent potentiation of VD3-induced monocytic differentiation.},
note = {Place: Netherlands},
keywords = {Arachidonate 5-Lipoxygenase/*genetics, Benzoquinones/pharmacology, Cell Differentiation/*drug effects, HL-60 Cells, Humans, Indoles/pharmacology, Lipoxygenase Inhibitors/*pharmacology, Monocytes/*cytology, p38 Mitogen-Activated Protein Kinases/*metabolism, Vitamin D/*analogs & derivatives/pharmacology},
pubstate = {published},
tppubtype = {article}
}
The treatment of human promyelocytic leukemia cell lines HL-60, and to some extent NB-4, with 1alpha,25-dihydroxyvitamin D(3) (VD3) induces differentiation toward the monocytic/macrophage lineage, demonstrated by the increased expression of CD11b and CD14, and the production of opsonized zymosan particles (OZP)-stimulated reactive oxygen species (ROS). Moreover, in more sensitive HL-60 cells, increased expression of 5-lipoxygenase (5-LPO), Mcl-1, IkappaB, and c-Jun, accompanied by the activation of p38 MAPK, was detected. These VD3 effects on HL-60 cell differentiation were significantly potentiated by 5-LPO inhibitors MK-886 and AA-861 and were inverted by SB202190 (SB), a p38 MAPK inhibitor. The inhibition of differentiation by SB was demonstrated by a reduction of CD14 expression and by a decrease in OZP-activated ROS production. These results indicated that p38 MAPK pathway is involved in 5-LPO inhibitors-dependent potentiation of VD3-induced monocytic differentiation.
2006
Andrysík, Zdenek; Machala, Miroslav; Chramostová, Katerina; Hofmanová, Jirina; Kozubík, Alois; Vondrácek, Jan
In: Toxicology and applied pharmacology, vol. 211, no. 3, pp. 198–208, 2006, ISSN: 0041-008X, (Place: United States).
Abstract | Links | BibTeX | Tags: *Epithelial Cells/cytology/drug effects/enzymology, *Liver/cytology/drug effects/enzymology, Animals, Apoptosis/*drug effects, Cell Cycle/drug effects, Cell Line, Cell Proliferation/drug effects, Enzyme Activation/drug effects, Enzyme Inhibitors/pharmacology, Extracellular Signal-Regulated MAP Kinases/*metabolism, JNK Mitogen-Activated Protein Kinases/metabolism, p38 Mitogen-Activated Protein Kinases/*metabolism, Phosphorylation, Polycyclic Aromatic Hydrocarbons/*toxicity, Rats
@article{andrysik_activation_2006,
title = {Activation of ERK1/2 and p38 kinases by polycyclic aromatic hydrocarbons in rat liver epithelial cells is associated with induction of apoptosis.},
author = {Zdenek Andrysík and Miroslav Machala and Katerina Chramostová and Jirina Hofmanová and Alois Kozubík and Jan Vondrácek},
doi = {10.1016/j.taap.2005.06.007},
issn = {0041-008X},
year = {2006},
date = {2006-03-01},
journal = {Toxicology and applied pharmacology},
volume = {211},
number = {3},
pages = {198–208},
abstract = {Deregulation of various signaling pathways, linked either to induction of cell proliferation or to modulation of cellular differentiation and apoptosis, has been proposed to contribute to carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). In the present study, we investigated effects of the PAHs previously shown to induce cell proliferation and/or apoptosis in contact-inhibited rat liver epithelial WB-F344 cells, with an aim to define the role of mitogen-activated protein kinases in both events. We found that only strong genotoxin dibenzo[a,l]pyrene (DBalP) activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 kinase, but not c-Jun N-terminal kinases (JNKs), at concentrations inducing both apoptosis and phosphorylation of p53 tumor suppressor at serine 15 residue. In contrast, the PAHs stimulating cell proliferation in WB-F344 cell line had no effect on activation of ERK1/2, p38 or JNKs. Synthetic inhibitors of ERK1/2 activation (U0126) or p38 kinase activity (SB203580) prevented both apoptosis and induction of p53 phosphorylation by DBalP. Pifithrin-alpha, inhibitor of p53 transcriptional activity, prevented induction of apoptosis and activation of ERK1/2 and p38. Taken together, our data suggest that both ERK1/2 and p38 are activated in response to DBalP and that they might be involved in regulation of cellular response to DNA damage induced by DBalP, while neither kinase is involved in the release from contact inhibition induced by PAHs.},
note = {Place: United States},
keywords = {*Epithelial Cells/cytology/drug effects/enzymology, *Liver/cytology/drug effects/enzymology, Animals, Apoptosis/*drug effects, Cell Cycle/drug effects, Cell Line, Cell Proliferation/drug effects, Enzyme Activation/drug effects, Enzyme Inhibitors/pharmacology, Extracellular Signal-Regulated MAP Kinases/*metabolism, JNK Mitogen-Activated Protein Kinases/metabolism, p38 Mitogen-Activated Protein Kinases/*metabolism, Phosphorylation, Polycyclic Aromatic Hydrocarbons/*toxicity, Rats},
pubstate = {published},
tppubtype = {article}
}
Deregulation of various signaling pathways, linked either to induction of cell proliferation or to modulation of cellular differentiation and apoptosis, has been proposed to contribute to carcinogenicity of polycyclic aromatic hydrocarbons (PAHs). In the present study, we investigated effects of the PAHs previously shown to induce cell proliferation and/or apoptosis in contact-inhibited rat liver epithelial WB-F344 cells, with an aim to define the role of mitogen-activated protein kinases in both events. We found that only strong genotoxin dibenzo[a,l]pyrene (DBalP) activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 kinase, but not c-Jun N-terminal kinases (JNKs), at concentrations inducing both apoptosis and phosphorylation of p53 tumor suppressor at serine 15 residue. In contrast, the PAHs stimulating cell proliferation in WB-F344 cell line had no effect on activation of ERK1/2, p38 or JNKs. Synthetic inhibitors of ERK1/2 activation (U0126) or p38 kinase activity (SB203580) prevented both apoptosis and induction of p53 phosphorylation by DBalP. Pifithrin-alpha, inhibitor of p53 transcriptional activity, prevented induction of apoptosis and activation of ERK1/2 and p38. Taken together, our data suggest that both ERK1/2 and p38 are activated in response to DBalP and that they might be involved in regulation of cellular response to DNA damage induced by DBalP, while neither kinase is involved in the release from contact inhibition induced by PAHs.