Abstract:
:Inhibition of p38MAPK alpha/beta is known to enhance 1,25-dihydroxyvitamin (1,25D)-induced monocytic differentiation, but the detailed mechanism of this effect was not clear. We now show that the enhancement of differentiation becomes apparent with slow kinetics (12-24 h). Interestingly, the inhibition of p38MAPK alpha/beta by their selective inhibitor SB202190 (SB) leads to an upregulated expression of p38MAPK isoforms gamma and delta in 1,25D-treated AML cells, in cell lines and in primary culture. Although the expression and activating phosphorylations of p38MAPK alpha are also increased by an exposure of the cells to SB, its kinase activity is blocked by SB, as shown by reduced levels of phosphorylated Hsp27, a downstream target of p38MAPK alpha. A positive role of p38MAPKs in 1,25D-induced differentiation is shown by the inhibition of differentiation by antisense oligonucleotides to all p38MAPK isoforms. Other principal branches of MAPK pathways showed early (6 h) activation of MEK/ERK by SB, followed by activation of JNK1/2 pathway and enhanced expression and/or activation of PU.1, ATF-2 differentiation-related transcription factors. Taken together with previous reports, the results indicate that 1,25D-induced differentiation is enhanced by the activation of at least three branches of MAPK pathways (ERK1/2; p38MAPK gamma/delta; JNK1/2). This activation may result from the removal of feedback inhibition of an upstream regulator of those pathways, when p38MAPK alpha and beta are inhibited by SB.
journal_name
Exp Cell Resjournal_title
Experimental cell researchauthors
Zhang J,Harrison JS,Studzinski GPdoi
10.1016/j.yexcr.2010.08.010subject
Has Abstractpub_date
2011-01-01 00:00:00pages
117-30issue
1eissn
0014-4827issn
1090-2422pii
S0014-4827(10)00404-0journal_volume
317pub_type
杂志文章abstract::The interaction of fluorescein-labeled nerve growth factor (NGF) with human melanoma cells (A875) has been studied in order to assess better methodology for rigorous NGF binding studies. The NGF was modified at a single carboxyl group with iodoacetamidofluorescein after reaction with carbodiimide and cystamine. The mo...
journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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pub_type: 杂志文章
doi:10.1006/excr.1995.1004
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journal_title:Experimental cell research
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journal_title:Experimental cell research
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