Benoxaprofen activates membrane-associated oxidative metabolism in human polymorphonuclear leucocytes by apparent modulation of protein kinase C.
1. The non-steroidal anti-inflammatory drug (NSAID) benoxaprofen at concentrations of 15, 30 and 60 micrograms ml-1 caused a dose-related activation of superoxide generation by human polymorphonuclear leucocytes (PMNL) in vitro. 2. The protein kinase C (PKC) inhibitor H-7 prevented benoxaprofen-mediated activation of superoxide generation by PMNL. 3. Benoxaprofen, by apparent substitution for phosphatidylserine, caused a dose-related activation of purified PKC from rat brain and in cytosolic extracts from human platelets. 4. Benoxaprofen-mediated stimulation of PMNL membrane-associated oxidative metabolism is due to apparent activation of PKC by this NSAID. These findings establish the molecular basis of the pro-oxidative properties of benoxaprofen.
Lukey
P T
PT
Department of Medical Microbiology, University of Pretoria, Republic of South Africa.
Anderson
R
R
Dippenaar
U H
UH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001711:Biotransformation; D002462:Cell Membrane / Q000201:enzymology; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D010084:Oxidation-Reduction; D010879:Piperazines / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D007546:Isoquinolines; D010879:Piperazines; D011422:Propionates; D047428:Protein Kinase Inhibitors; D013481:Superoxides; C011677:benoxaprofen; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C