title: Homocysteine enhances superoxide anion release and NADPH oxidase assembly by human neutrophils. Effects on MAPK activation and neutrophil migration.
abstract: Hyperhomocysteinaemia has recently been recognized as a risk factor of cardiovascular disease. However, the action mechanisms of homocysteine (Hcy) are not well understood. Given that Hcy may be involved in the recruitment of monocytes and neutrophils to the vascular wall, we have investigated the role of Hcy in essential functions of human neutrophils. We show that Hcy increased superoxide anion (O2*-) release by neutrophils to the extracellular medium, and that this effect was inhibited by superoxide dismutase and diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase activity. The enzyme from rat peritoneal macrophages displayed a similar response. These effects were accompanied by a time-dependent increased translocation of p47phox and p67phox subunits of NADPH oxidase to the plasma membrane. We also show that Hcy increased intracellular H2O2 production by neutrophils, that Hcy enhanced the activation and phosphorylation of mitogen-activated protein kinases (MAPKs), specifically p38-MAPK and ERK1/2, and that the migration of neutrophils was increased by Hcy. Present results are the first evidence that Hcy enhances the oxidative stress of neutrophils, and underscore the potential role of phagocytic cells in vascular wall injury through O2*- release in hyperhomocysteinaemia conditions.
authors.affiliation: Departamento de Bioquímica Médica y Biología Molecular, Universidad de Sevilla, Avda. Sánchez Pizjuán 4, 41009 Sevilla, Spain.
authors.forename: Moisés
authors.initials: M
authors.lastname: Alvarez-Maqueda
authors.forename: Rajaa
authors.initials: R
authors.lastname: El Bekay
authors.forename: Javier
authors.initials: J
authors.lastname: Monteseirín
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Alba
authors.forename: Pedro
authors.initials: P
authors.lastname: Chacón
authors.forename: Antonio
authors.initials: A
authors.lastname: Vega
authors.forename: Consuelo
authors.initials: C
authors.lastname: Santa María
authors.forename: Juan R
authors.initials: JR
authors.lastname: Tejedo
authors.forename: José
authors.initials: J
authors.lastname: Martín-Nieto
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Bedoya
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pintado
authors.forename: Francisco
authors.initials: F
authors.lastname: Sobrino
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000201:enzymology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D009861:Onium Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
chemical_list: D009861:Onium Compounds; D006710:Homocysteine; D013481:Superoxides; C007517:diphenyleneiodonium; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases