Inhibition of COX activity by NSAIDs or ascorbate increases cAMP levels and enhances differentiation in 1alpha,25-dihydroxyvitamin D3-induced HL-60 cells.
Arachidonic acid metabolism is modulated during differentiation induced by 1alpha,25(OH)(2)D(3) in HL-60 cells. Antioxidants that affect arachidonic acid metabolism enhance this differentiation program. Ascorbate also enhances differentiation in 1alpha,25(OH)(2)D(3)-induced cells depending on the induction of cAMP. The aim of this work was to study if this cAMP rise depends on modulation of arachidonic acid metabolism by ascorbate. Cyclooxygenase inhibitors, indomethacin and aspirin, increased cAMP levels and also enhanced 1alpha,25(OH)(2)D(3)-induced differentiation in HL-60 cells. Ascorbate did not affect the release of arachidonic acid-derived metabolites but decreased the levels of TXB(2) and PGE(2), suggesting the inhibition of cyclooxygenase. On the other hand, free arachidonic acid increased both cAMP levels and differentiation in the absence or presence of 1alpha,25(OH)(2)D(3). Neither cyclooxygenase inhibitors nor ascorbate modified AA effect. Then, inhibition of cyclooxygenase activity by ascorbate could accumulate free arachidonic acid or other metabolites that increase cAMP levels and enhance differentiation in 1alpha,25(OH)(2)D(3)-induced HL-60 cells.
López-Lluch
G
G
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide, 41013 Sevilla, Spain. glopllu@upo.es
Fernández-Ayala
D J M
DJ
Alcaín
F J
FJ
Burón
M I
MI
Quesada
J M
JM
Navas
P
P
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D010084:Oxidation-Reduction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D016718:Arachidonic Acid; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D001205:Ascorbic Acid