Effects of the protein kinase C inhibitor H-7 and calmodulin antagonist W-7 on superoxide production in growing and resting human histiocytic leukemia cells (U937).
Serum, phorbol 12,13-didecanoate (PDD) and 1-oleoyl-2-acetoy-sn-glycerol (OAG) stimulated O2- release in human histiocytic leukemia U937 cells. The kinetics of O2- release caused by PDD but not by serum or OAG in growing cells differed from those in resting cells. Both the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl) 2-methylpiperidine (H-7) and calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) reduced the superoxide generation induced by these stimuli. H-7 inhibited the O2- release either from growing or resting cells but the effect of W-7 varied according to the growth phase. From these results, it is suggested that activation of protein kinase C and calmodulin-dependent process has an important role in O2(-)-release induced by serum, OAG and PDD, and that the mechanism for PDD-induced O2(-)-release is different in growing and resting cells.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002455:Cell Division; D002460:Cell Line; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D007951:Leukemia, Myeloid; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
D002147:Calmodulin; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D013481:Superoxides; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C