title: Apocynin increases glutathione synthesis and activates AP-1 in alveolar epithelial cells.
abstract: Apocynin (4-hydroxy-3-methoxy-acetophenone) is a potent intracellular inhibitor of superoxide anion production in neutrophils. In this study, we studied the effect of apocynin on the regulation of the antioxidant glutathione (GSH) and activation of the transcription factor AP-I in human alveolar epithelial cells (A549). Apocynin enhanced intracellular GSH by increasing gamma-glutamylcysteine synthetase activity in A549 cells. Apocynin also increased the expression of gamma-GCS heavy subunit mRNA. This was associated with increased AP-1 DNA binding as measured by the electrophoretic mobility shift assay. These data indicate that apocynin displays antioxidant properties, in part, by increasing glutathione synthesis through activation of AP-1.
authors.affiliation: Department of Pulmonology, Leiden University Medical Centre, The Netherlands.
authors.forename: T S
authors.initials: TS
authors.lastname: Lapperre
authors.forename: L A
authors.initials: LA
authors.lastname: Jimenez
authors.forename: F
authors.initials: F
authors.lastname: Antonicelli
authors.forename: E M
authors.initials: EM
authors.lastname: Drost
authors.forename: P S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: J
authors.initials: J
authors.lastname: Stolk
authors.forename: W
authors.initials: W
authors.lastname: MacNee
authors.forename: I
authors.initials: I
authors.lastname: Rahman
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D017931:DNA Primers; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000096:biosynthesis*; D006801:Humans; D011485:Protein Binding; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*