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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1992-10-22
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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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyadenosines,
http://linkedlifedata.com/resource/pubmed/chemical/Dimethyl Sulfoxide,
http://linkedlifedata.com/resource/pubmed/chemical/Hemoglobins,
http://linkedlifedata.com/resource/pubmed/chemical/Homocysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Methionine,
http://linkedlifedata.com/resource/pubmed/chemical/N(6)-methyladenosine,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/cordycepin
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
927-36
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1530661-Adenine,
pubmed-meshheading:1530661-Adenosine,
pubmed-meshheading:1530661-Animals,
pubmed-meshheading:1530661-Cell Differentiation,
pubmed-meshheading:1530661-Cell Division,
pubmed-meshheading:1530661-Cell Survival,
pubmed-meshheading:1530661-Deoxyadenosines,
pubmed-meshheading:1530661-Dimethyl Sulfoxide,
pubmed-meshheading:1530661-Hemoglobins,
pubmed-meshheading:1530661-Homocysteine,
pubmed-meshheading:1530661-Leukemia, Erythroblastic, Acute,
pubmed-meshheading:1530661-Methionine,
pubmed-meshheading:1530661-Mice,
pubmed-meshheading:1530661-RNA, Messenger,
pubmed-meshheading:1530661-Structure-Activity Relationship,
pubmed-meshheading:1530661-Tumor Cells, Cultured
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pubmed:year |
1992
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pubmed:articleTitle |
Analysis of the inhibition of commitment of murine erythroleukemia (MEL) cells to terminal maturation by N6-methyladenosine.
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pubmed:affiliation |
Department of Pharmaceutical Sciences, School of Health Sciences, Aristotle University of Thessaloniki, Greece.
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pubmed:publicationType |
Journal Article,
Comparative Study
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