alpha-Tocopherol inhibits the respiratory burst in human monocytes: attenuation of p47phox membrane translocation and phosphorylation

• Published in: The Journal of biological chemistry Vol. 273; no. 49; pp. 32801 - 32805
• Main Authors: Cachia, O. (Insitut de Biologie, Montpellier, France.), El Benna, J, Pedruzzi, E, Descomps, B, Gougerot-Pocidalo, M.A, Leger, C.L
• Format: Journal Article
• Language: English
• Published: 04.12.1998
• Subjects: ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; CELL MEMBRANES; ENZYMIC ACTIVITY; FOSFORILACION; FREE RADICALS; GENERO HUMANO; GENRE HUMAIN; INHIBICION; INHIBITION; MANKIND; MEMBRANAS CELULARES; MEMBRANE CELLULAIRE; METABOLISME DES PROTEINES; METABOLISMO PROTEICO; MONOCITOS; MONOCYTE; MONOCYTES; NADPH OXIDASE; OXIDOREDUCTASES; OXIDORREDUCTASAS; OXIGENO; OXYDOREDUCTASE; OXYGEN; OXYGENE; PHOSPHORYLATION; PLASMA MEMBRANES; PROTEIN KINASE; PROTEIN KINASE C; PROTEIN METABOLISM; PROTEIN TRANSPORT; PROTEINA QUINASA; PROTEINE KINASE; RADICAL LIBRE; RADICALES LIBRES; SERINA; SERINE; SUPEROXIDE ANIONS; TOCOFEROLES; TOCOPHEROL; TOCOPHEROLS
• ISSN: 0021-9258; 1083-351X

Vitamin E ( alpha -tocopherol), one of the most important natural antioxidants, is assumed to be beneficial in the prevention of cardiovascular diseases. alpha -Tocopherol exhibits acyl-peroxyl-radical scavenger properties and exerts cell-mediated actions in the hemovascular compartment, such as inhibition of superoxide anion (O- sub(2)) production by leukocytes. The aim of this study was to examine the mechanism underlying the inhibitory effect of alpha -tocopherol on O- sub(2) production by human monocytes. In activated monocytes O- sub(2) is produced by the NADPH-oxidase enzyme complex. The oxidase activation elicited by phorbol myristate acetate (PMA) requires membrane translocation of several cytosolic factors. We found that in human PMA-stimulated adherent monocytes alpha -tocopherol (but not beta -tocopherol) inhibited O- sub(2) production in intact cells but had no effect on a membrane preparation containing activated NADPH-oxidase, suggesting that alpha -tocopherol impairs the assembly process of the enzyme complex. We showed that translocation and phosphorylation of the cytosolic factor p47phox were reduced in monocytes preincubated with alpha -tocopherol. We verified that the tryptic phosphopeptide map of monocyte p47phox was similar to that of neutrophil p47phox, indicating that several serine residues were phosphorylated. Peptides whose phosphorylation is dependent on protein kinase C (PKC) were phosphorylated to a lesser degree when p47phox was immunoprecipitated from alpha -tocopherol-treated monocytes. In vitro, the activity of PKC from monocytes was inhibited by alpha -tocopherol in a specific manner compared with that of beta -tocopherol or Trolox registered . Membrane translocation of PKC was not affected. These results show that alpha -tocopherol inhibits O- sub(2) production by human adherent monocytes by impairing the assembly of the NADPH-oxidase and suggest that the inhibition of phosphorylation and translocation of the cytosolic factor p47phox results from a decrease in PKC activity.