Inhibition of NADPH oxidase-mediated superoxide radical formation in PMA-stimulated human neutrophils by 4-hydroxynonenal--binding to -SH and -NH2 groups.
4-Hydroxynonenal (HNE), a major lipid peroxidation product, effectively inhibits the superoxide radical formation by NADPH oxidase of phorbol myristate acetate (PMA)--stimulated human PMNL. The I50 value for the inhibition of NADPH oxidase-mediated superoxide radical formation by 4-hydroxynonenal was found to be 19 microM. The HNE inhibition involves the reaction with both -SH and -NH2 groups. Superoxide formation as final result of the NADPH oxidase cascade was almost completely restored by addition of dithiothreitol. In presence of hydroxylamine only a minor restoration of superoxide radical formation was found. A combination of dithiothreitol and hydroxylamine yielded the greatest recovery. Two other aldehydes with the same chain length as HNE but different binding to lysine, histidine and cysteine residues, trans-2,3-nonenal and nonanal, gave I50 values for the inhibition of NADPH oxidase-mediated superoxide formation rate of 110 microM or > 300 microM, respectively.
Siems
W G
WG
Herzog-Julius Hospital of Rheumatology and Orthopaedics, Bad Harzburg, Germany.
Capuozzo
E
E
Verginelli
D
D
Salerno
C
C
Crifò
C
C
Grune
T
T
D000447:Aldehydes / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000447:Aldehydes; D002273:Carcinogens; D015853:Cysteine Proteinase Inhibitors; D005609:Free Radicals; D013481:Superoxides; D019255:NADPH Oxidases; C027576:4-hydroxy-2-nonenal; D013755:Tetradecanoylphorbol Acetate