title: Characteristics of cyclic AMP enhancement of retinoic acid induction of increased transglutaminase activity in HL60 cells.
abstract: When the human myeloid leukemia cell line (HL60) is induced to differentiate with retinoic acid (RA), there is a concentration-dependent increase in transglutaminase (TGase) activity which peaks on day 5. While dibutyryl 3',5'-cyclic adenosine monophosphate (db-cAMP) alone produced only a slight increase in TGase activity in HL60 cells, the concomitant addition of db-cAMP (100 microM) with RA (10(-12)-10(-4) M) potentiates RA induction of TGase activity. Maximal increases in TGase activity (2- to 10-fold) were observed with 10(-4)-10(-7) M RA and when db-cAMP was present from 24 to 48 h after the addition of RA. The cyclic nucleotide enhancement was dose-dependent from 10 to 100 microM of cAMP. Less marked increases were observed with 8-bromo-cAMP and with the phosphodiesterase inhibitor theophylline. Although the simultaneous addition of PGE1 or PGE2 (10(-8)-10(-6) M) produced no enhancement of RA-induced TGase activity, adding PGE1 or PGE2 24 or 48 h following RA treatments produced an enhancement of TGase activity. The phosphodiesterase inhibitor potentiated the increases produced by db-cAMP and the prostaglandins. Dibutyryl cAMP enhanced the ability of RA to induce the cells to reduce nitroblue tetrazolium (NBT), a functional measure of differentiation, at lower concentrations of RA and with shorter treatment durations. cAMP potentiates RA-induced TGase activity in HL60 cells and the combination appears to be associated with enhanced RA-induced differentiation.
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid; D013806:Theophylline / Q000494:pharmacology; D011503:Transglutaminases / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology*
chemical_list: D002087:Butyrates; D020148:Butyric Acid; D015124:8-Bromo Cyclic Adenosine Monophosphate; D014212:Tretinoin; D003994:Bucladesine; D013806:Theophylline; D000242:Cyclic AMP; D011503:Transglutaminases; D000527:Alprostadil; D000241:Adenosine; D015232:Dinoprostone