Inhibition of NADPH Oxidase-Mediated Superoxide Radical Formation in PMA-Stimulated Human Neutrophils by 4-Hydroxynonenal– Binding to -SH and -NH₂ Groups

Werner G. Siems Herzog-ulius Hospital of Rheumatology and Orthopaedics, Kurhausstraβe 13–17, 0-38655, Bad HarzburgGermany

Elisabetta Capuozzò Department of Biochenzical Sciences, University of Rome, P.Ie A. Moro, 1-00185, Rome, Italy

Daniela Verginelli Department of Biochenzical Sciences, University of Rome, P.Ie A. Moro, 1-00185, Rome, Italy

Costantino Salerno Laboratovy of Clinical Biochemisty University of Rome, P.Ie A. Moro, 1-00185, Rome, Italy

Carlo Crifo Department of Biochenzical Sciences, University of Rome, P.Ie A. Moro, 1-00185, Rome, Italy

Tilman Grune Clinics of Physicd Therapy and Rehabilitation, University Hospital Charité Medical Faculty of the Humboldt University, Schumannstvape 20–21, 0-10098, Berlin, Germany

Abstract

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 I,_o value for the inhibition of NADPH oxidase-mediated superoxide radical formation by 4-hydroxynonenal was found to be 19 pM. 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 hydroxy-lamine 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 I,_o values for the inhibition of NADPH oxidase-mediated superoxide formation rate of 110 pM or >300 pM, respectively.

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Inhibition of NADPH Oxidase-Mediated Superoxide Radical Formation in PMA-Stimulated Human Neutrophils by 4-Hydroxynonenal– Binding to -SH and -NH₂ Groups

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Inhibition of NADPH Oxidase-Mediated Superoxide Radical Formation in PMA-Stimulated Human Neutrophils by 4-Hydroxynonenal– Binding to -SH and -NH2 Groups

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Inhibition of NADPH Oxidase-Mediated Superoxide Radical Formation in PMA-Stimulated Human Neutrophils by 4-Hydroxynonenal– Binding to -SH and -NH₂ Groups