Induction of hemoglobin synthesis by xylosyladenine in murine erythroleukemia cells. Metabolism of xylosyladenine and effects on transmethylation.
The adenosine analog xylosyladenine is a potent inducer of hemoglobin synthesis in Friend virus-infected murine erythroleukemia (MEL) cells. In cultures treated with 0.1 microM xylosyladenine and an inhibitor of adenosine deaminase, 80% of the cells accumulated hemoglobin. Under these conditions, cell growth was inhibited by 50%. No effect was observed in the absence of adenosine deaminase inhibition. An adenosine kinase-deficient MEL subline was isolated and was found to be resistant to induction by xylosyladenine. Treated cells accumulated substantial amounts of the xylofuranosyl analogs of ATP, S-adenosylmethionine, and S-adenosylhomocysteine, indicating that metabolites of xylosyladenine participate in S-adenosylmethionine-mediated transmethylation reactions. Measurements of in vivo nucleic acid methylation showed that xylosyladenine causes a marked inhibition of 2'-O-methyluridine, 2'-O-methylcytidine, 5-methyluridine, and 5-methylcytidine formation in the RNA of treated cells. DNA methylation was not inhibited. These data suggest that the xylofuranosyl analogs of S-adenosylmethionine and/or S-adenosylhomocysteine can inhibit intracellular RNA methylation in MEL cells while having little or no such effect on DNA methylation.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis*; D007700:Kinetics; D007942:Leukemia, Experimental / Q000378:metabolism*; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D008745:Methylation; D051379:Mice
D006454:Hemoglobins; C014251:9-xylosyladenine; D008716:Methionine Adenosyltransferase; D000241:Adenosine; D004121:Dimethyl Sulfoxide