Inhibition of NADPH oxidase-mediated superoxide radical formation in PMA-stimulated human neutrophils by 4-hydroxynonenal--binding to -SH and -NH2 groups

• Published in: Free radical research Vol. 27; no. 4; p. 353
• Main Authors: Siems, W G, Capuozzo, E, Verginelli, D, Salerno, C, Crifò, C, Grune, T
• Format: Journal Article
• Language: English
• Published: England 01-01-1997
• Subjects: Aldehydes - pharmacology; Carcinogens - pharmacology; Cysteine Proteinase Inhibitors - pharmacology; Free Radicals - metabolism; Humans; NADPH Oxidases - antagonists & inhibitors; NADPH Oxidases - metabolism; Neutrophil Activation - drug effects; Neutrophils - metabolism; Superoxides - metabolism; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 1071-5762
• DOI: 10.3109/10715769709065774

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.