Biochemical and Biophysical Research Communications
The time-course of cyclic AMP signaling is critical for leukemia U-937 cell differentiation☆,☆☆
Section snippets
Materials and methods
Materials. Cell culture medium, isobutylmethylxanthine (IBMX), cAMP, dbcAMP, forskolin, prostaglandin E2 (PGE2), Fura 2 acetoxymethyl ester (Fura 2-AM), bovine serum albumin (BSA), and rhC5a were obtained from Sigma Chemical Company (St. Louis, MO). Fetal calf serum was purchased from Natocor (Argentina). Amthamine and 6[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl)heptane-carboxamide (HTMT dimaleate) were from Tocris Cookson (Ballwin, MO). H-7 was obtained from Calbiochem (La Jolla,
Cyclic AMP elevation in response to different agents in U-937 cells
Cyclic AMP levels were induced in U-937 cells by amthamine and PGE2, two agonists that stimulate G protein-coupled receptors (GPCR), histamine H2 receptor, and PGE2 receptors, respectively. Forskolin, a direct adenylyl cyclase-activating agent, was also used to increase cAMP levels. All agents elevated cAMP levels in a concentration-dependent manner, with EC50 values of 465 ± 95 nM (n=5), 39 ± 6 nM (n=3), and 40 ± 7 μM (n=3) for amthamine, PGE2, and forskolin, respectively. These agents evoked similar
Discussion
The formation of the different blood cells is essential for the development of a normal individual. New blood cells belonging to different cell lineages are formed from stem cells not only during embryogenesis but also during the adult lifetime. Abnormalities in the normal developmental program of blood cell formation result in various types of hematological diseases, including leukemia which involves an uncoupling of the regulatory mechanisms that normally integrate cell proliferation with
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2011, Journal of Biological ChemistryCitation Excerpt :In mouse myeloid leukemia cells as well as in the human promonocytic U937 cell line, dibutyryl cyclic AMP (Bt2cAMP) induces monocytic differentiation (5, 6). We previously reported that the time course of cAMP signaling is critical for leukemia U937 cell differentiation (6, 7). Furthermore, despite a large increase in cAMP levels mediated by H2 receptor activation, U937 cells trigger PDE4 activation and G-protein-coupled receptor kinase 2 (GRK2)-mediated receptor desensitization.
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This study was supported by grants from the Universidad Buenos Aires (Grant B022) and Consejo Nacional de Investigaciones Cientı́ficas y Técnicas (PICT 9805-03514).
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Abbreviations: APL, acute promyelocytic leukemia; cAMP, cyclic adenosine monophosphate; dbcAMP, dibutyryl cAMP; PDE, phosphodiesterase; GRK, G protein-coupled receptor kinase; GPCR, G protein-coupled receptor; IBMX, isobutylmethylxanthine; PGE2, prostaglandin E2; Fura 2-AM, Fura 2 acetoxymethyl ester; BSA, bovine serum albumin; rhC5a, recombinant human C5a; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide.