Positive modulation of hemoglobin, heme, and transferrin receptor synthesis by murine interferon-alpha and -beta in differentiating Friend cells. Pivotal role of heme synthesis.
Administration of highly purified preparations of murine interferon (IFN)-alpha 1, -alpha 4, -alpha 6, or -beta to Friend leukemia cells induced to differentiate by dimethyl sulfoxide leads to a 100% increase of benzidine-positive (B+) cells. Different efficiencies for the two IFN species have been observed; a 10-fold higher dose of IFN-alpha is needed for stimulation of hemoglobin production and inhibition of cell growth as compared with IFN-beta. Both species of IFN induce a substantial increase in heme, hemoglobin, and transferrin receptor levels. In vitro run-on transcription assays indicate that IFN-beta moderately stimulates transcription of the alpha-globin gene but not the transferrin receptor gene. It is postulated that IFN induces the enhancing effect on differentiation via a marked increase of heme synthesis and number of transferrin receptors, which in turn leads to an enhancement of globin chain synthesis. In this regard, the negative feedback reported in a variety of other cell types for the regulation of transferrin receptor expression by heme does not seem to be operative in maturing Friend erythroleukemia cells, which present evidence for a positive mechanism.
Battistini
A
A
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Marziali
G
G
Albertini
R
R
Habetswallner
D
D
Bulgarini
D
D
Coccia
E M
EM
Fiorucci
G
G
Romeo
G
G
Orsatti
R
R
Testa
U
U
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D006418:Heme / Q000096:biosynthesis* / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis*; D007370:Interferon Type I / Q000494:pharmacology*; D007700:Kinetics; D007942:Leukemia, Experimental; D051379:Mice; D011990:Receptors, Transferrin / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
D006454:Hemoglobins; D007370:Interferon Type I; D011990:Receptors, Transferrin; D006418:Heme; D005914:Globins; D004121:Dimethyl Sulfoxide