|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
4
|
|
pubmed:dateCreated |
2002-12-10
|
|
pubmed:abstractText |
Hydroxyurea (HU) has been shown to increase the proportion of fetal haemoglobin (HbF) in most sickle cell patients. A low-dosage regimen increased total haemoglobin (Hb) levels in some thalassaemia intermedia patients by preferentially increasing beta-globin biosynthesis. To further characterize these apparent dose-dependent effects of HU, we examined erythroid cells exposed to HU (5-100 micro mol/l) in two-phase liquid culture. Low doses (from 5 to 25 micro mol/l) increased Hb levels by up to 2.7-fold, and a high dose (100 micro mol/l) increased Hb levels when added at d 3-6 of phase II, with no significant changes in response to HU during the late stage of phase II culture (> or = 9 d). HU exposure during d 0-3 of phase II culture increased the number of erythroid colonies to a maximum of fivefold at 5 micro mol/l HU. GATA-1 mRNA was downregulated at a high dose and GATA-2 was dose dependently upregulated over a lower dosage range. Treatment with 100 micro mol/l HU dramatically upregulated the death receptor DR-5, caspase 3, as determined by cDNA microarray analysis. In contrast, 10 micro mol/l HU modestly upregulated mRNA levels of the early growth response gene. Our results suggest that HU exerts concentration-dependent effects on HbF production and erythropoiesis and that these two effects are mediated by distinct molecular mechanisms.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Erythroid-Specific DNA-Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/GATA1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GATA2 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/GATA2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Globins,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyurea,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0007-1048
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
119
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1098-105
|
|
pubmed:dateRevised |
2008-11-21
|
|
pubmed:meshHeading |
pubmed-meshheading:12472594-Adult,
pubmed-meshheading:12472594-Cell Culture Techniques,
pubmed-meshheading:12472594-Cell Differentiation,
pubmed-meshheading:12472594-Chromatography, High Pressure Liquid,
pubmed-meshheading:12472594-Colony-Forming Units Assay,
pubmed-meshheading:12472594-DNA-Binding Proteins,
pubmed-meshheading:12472594-Dose-Response Relationship, Drug,
pubmed-meshheading:12472594-Erythroid Precursor Cells,
pubmed-meshheading:12472594-Erythroid-Specific DNA-Binding Factors,
pubmed-meshheading:12472594-Erythropoiesis,
pubmed-meshheading:12472594-GATA1 Transcription Factor,
pubmed-meshheading:12472594-GATA2 Transcription Factor,
pubmed-meshheading:12472594-Gene Expression Profiling,
pubmed-meshheading:12472594-Gene Expression Regulation,
pubmed-meshheading:12472594-Globins,
pubmed-meshheading:12472594-Humans,
pubmed-meshheading:12472594-Hydroxyurea,
pubmed-meshheading:12472594-Nucleic Acid Synthesis Inhibitors,
pubmed-meshheading:12472594-RNA, Messenger,
pubmed-meshheading:12472594-Transcription Factors
|
|
pubmed:year |
2002
|
|
pubmed:articleTitle |
Hydroxyurea exerts bi-modal dose-dependent effects on erythropoiesis in human cultured erythroid cells via distinct pathways.
|
|
pubmed:affiliation |
The Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
