title: Metabolism of 4-hydroxy-2-nonenal in human polymorphonuclear leukocytes.
abstract: Intracellular metabolism of 4-hydroxy-2-nonenal (HNE), a major product and mediator of oxidative stress and inflammation, is analyzed in resting and fMLP-stimulated human polymorphonuclear leukocytes (PMNL), where this compound is generated during activation of the respiratory burst. HNE consumption rate in PMNL is very low, if compared to other cell types (rat hepatocytes, rabbit fibroblasts), where HNE metabolism is always an important part of secondary antioxidative defense mechanisms. More than 98% of HNE metabolites are identified. The pattern of HNE intermediates is quite similar in stimulated and resting PMNL - except for higher water formation in resting PMNL - while the initial velocity of HNE degradation is somewhat higher in resting cells, 0.44 instead of 0.28 nmol/(min×10(6) cells). The main products of HNE metabolism are 4-hydroxynonenoic acid (HNA), 1,4-dihydroxynonene (DHN) and the glutathione adducts with HNE, HNA, and DHN. Protein-bound HNE and water account for about 3-4% of the total HNE derivatives in stimulated cells, while in resting cells protein-bound HNE and water are 4% and 20%, respectively. Cysteinyl-glycine-HNE adduct and mercapturic acids contribute to about 5%.
authors.affiliation: Department of Physiotherapy and Gerontology, KortexMed Institute of Medical Education, Bad Harzburg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Siems
authors.forename: Carlo
authors.initials: C
authors.lastname: Crifo
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Capuozzo
authors.forename: Koji
authors.initials: K
authors.lastname: Uchida
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
authors.forename: Costantino
authors.initials: C
authors.lastname: Salerno
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D004151:Dipeptides / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D006880:Hydroxy Acids / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D011817:Rabbits; D051381:Rats
chemical_list: C406867:4-hydroxynonenoic acid; D000447:Aldehydes; D004151:Dipeptides; D005231:Fatty Acids, Unsaturated; D006880:Hydroxy Acids; C028505:cysteinylglycine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005978:Glutathione; C027576:4-hydroxy-2-nonenal; D000111:Acetylcysteine