The time-course of cyclic AMP signaling is critical for leukemia U-937 cell differentiation.
The regulation of the cAMP signaling is intimately involved in several cellular processes, including cell differentiation. Here, we provide strong evidence supporting that the time-course of cAMP signal is critical for leukemia U-937 cell differentiation. Three stimulating-cAMP agents were used to analyze the correlation between cAMP time-course and cell differentiation. All three agents denoted similar cAMP maximal responses in dose-response experiments. The kinetic of desensitization showed differential characteristics, while H2 receptor desensitized homologously without affecting PGE2 or forskolin effect, PGE2 response showed mixed desensitization characterized by a homologous initial phase followed by a heterologous phase. Regarding forskolin, long-term stimuli attenuated PGE2 and H2 agonist response without affecting adenylyl cyclase activity. In the absence of phosphodiesterase inhibitors, the three agents induced similar maximal cAMP levels after 5 min, but only that induced by the H2 agonist returned to basal levels. Consistent with this observation, H2 agonist was not able to induce U-937 cell maturation in contrast to PGE2 and forskolin, supporting the importance of time-course signaling in the determination of cell behavior.
Shayo
Carina
C
Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina. cshayo@dna.uba.ar
Legnazzi
Bibiana Lemos
BL
Monczor
Federico
F
Fernández
Natalia
N
Riveiro
María Eugenia
ME
Baldi
Alberto
A
Davio
Carlos
C
D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D015936:Complement C5a / Q000235:genetics / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000096:biosynthesis; D011970:Receptors, Histamine H2 / Q000187:drug effects; D018078:Receptors, Prostaglandin E / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D020298:U937 Cells
D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D011970:Receptors, Histamine H2; D018078:Receptors, Prostaglandin E; D011994:Recombinant Proteins; D013844:Thiazoles; C076207:amthamine; D005576:Colforsin; D015936:Complement C5a; D000242:Cyclic AMP; D015232:Dinoprostone; D002118:Calcium