Apocynin increases glutathione synthesis and activates AP-1 in alveolar epithelial cells

Apocynin (4-hydroxy-3-methoxy-acetophenone) is a potent intracellular inhib itor of superoxide anion production in neutrophils. In this study, we studi ed the effect of apocynin on the regulation of the antioxidant glutathione (GSH) and activation of the transcription factor AP-1 in human alveolar epi thelial cells (A549). Apocynin enhanced intracellular GSH by increasing gam ma-glutamylcysteine synthetase activity in A549 cells. Apocynin also increa sed the expression of gamma-GCS heavy subunit mRNA. This was associated wit h increased AP-1 DNA binding as measured by the electrophoretic mobility sh ift assay. These data indicate that apocynin displays antioxidant propertie s, in part, by increasing glutathione synthesis through activation of AP-1. (C) 1999 Federation of European Biochemical Societies.