Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1992-10-22
pubmed:abstractText
Treatment of cultured murine erythroleukemia (MEL or Friend) cells with N6-methylated derivatives of adenosine inhibited erythroid cell differentiation induced by various agents. N6-Methyladenosine (N6mAdo) inhibited initiation of commitment to terminal maturation and prevented accumulation of hemoglobin in a concentration-dependent manner. Treatment with N6mAdo slowed cell growth without causing substantial inhibition in the rate of DNA synthesis and a marked decrease in viability and clonogenic potential of MEL cells. Furthermore, N6mAdo decreased the cytoplasmic accumulation of beta(major) globin mRNA and affected its structural integrity in MEL cells. Cells pre-exposed to N6mAdo failed to initiate commitment as early as control cells upon challenge with the inducer dimethyl sulfoxide. N6mAdo-induced inhibition of commitment was not reversed but rather was potentiated by the presence of adenine, L-homocysteine and/or L-methionine, agents involved in the active methylation cycle. To this respect, N6mAdo-induced inhibition of commitment was found to be different from that caused by cordycepin (3'-deoxyadenosine, an inhibitor of RNA methylation and mRNA polyadenylation). The latter inhibition was fully reversed by the addition of L-methionine. These findings indicate that N6-methyladenosine: (a) blocks a central process that is required for initiation of commitment; and (b) decreases accumulation of beta (major) globin mRNA, causes mRNA degradation and prevents hemoglobin synthesis. Due to the differential sensitivity of N6mAdo- and cordycepin-induced blockade of commitment to L-methionine, these agents inhibit commitment by acting via two different mechanisms impinging on the final pathway of MEL erythroid cell maturation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
927-36
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Analysis of the inhibition of commitment of murine erythroleukemia (MEL) cells to terminal maturation by N6-methyladenosine.
pubmed:affiliation
Department of Pharmaceutical Sciences, School of Health Sciences, Aristotle University of Thessaloniki, Greece.
pubmed:publicationType
Journal Article, Comparative Study