Linked Life Data

7646543

Source:http://linkedlifedata.com/resource/pubmed/id/7646543

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-9-19
pubmed:abstractText
To investigate the mechanisms that may be involved in zidovudine (AZT)-induced hematopoietic toxicity, spleen cells isolated from phenylhydrazine-treated anemic mice or murine bone marrow erythroid progenitor cells were treated with AZT (1-10 microM) for 24 hr. A concentration-dependent inhibition of the binding of 125I-labeled erythropoietin (Epo) was observed, suggesting down-regulation of Epo receptors. To determine if this effect is due to modulation of the levels of Epo receptor mRNA and to assess the effect of AZT on the expression of protooncogenes, mRNA levels were monitored by the slot blot hybridization technique. AZT caused a concentration-dependent inhibition in the levels of the mRNA of Epo receptors and c-fos, whereas the level of c-myc mRNA was unaffected. AZT also inhibited protein kinase C (PKC) activity in a concentration- and time-dependent manner, causing 50% inhibition at 10 microM within 3 hr. Simultaneous addition of Epo or interleukin-3 (IL-3) partially reversed the inhibitory effects of AZT on the levels of the mRNAs and on PKC activity; however, a combination of Epo and IL-3 was significantly more effective. These studies demonstrate that (i) AZT-induced down-regulation of Epo receptors and c-fos expression coupled with inhibition of Epo receptor-mediated signal transduction through PKC are significant contributory factors to AZT-induced erythroid toxicity, and (ii) these inhibitory effects can be overcome by treatment with a combination of Epo and IL-3.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
413-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Inhibitory effects of zidovudine in erythroid progenitor cells. Reversal with a combination of erythropoietin and interleukin-3.
pubmed:affiliation
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.