Brefeldin A detoxification in rat extraorbital lacrimal glands.

Abstract

Brefeldin A (BFA) has been extensively used, during the last 10 years, as a tool for the study of intracellular trafficking mechanisms. This antibiotic, produced by several fungi, was found to inhibit intracellular protein transit and to disrupt the Golgi apparatus structure. Although it is now well established that BFA acts by preventing the association of the ADP ribosylation factor (ARF) to the Golgi membranes, its molecular target has not yet been isolated and characterized. One major feature of BFA is that its action is rapidly reversible after removal of the drug.1 Nevertheless, a spontaneous reversion was observed in hepatocyte cultures even in the presence of the drug.2,3 This suggested that BFA could be metabolized to an inactive form. More recently, Brüning et al.4 showed that, in Chinese hamster ovary cells, BFA could be converted to glutathione derivatives by glutathione-S-transferase, a well-known enzyme involved in the detoxification of numerous compounds.5,6 In the general glutathionebased detoxification pathway, the toxic compound is intracellularly converted to a glutathione derivative by glutathione-S-transferase. The glutathione derivative is then extruded from the cells and extracellularly converted to a cysteine derivative by γ-glutamyl transpeptidase.KeywordsChinese Hamster Ovary CellLacrimal GlandGolgi MembraneDetoxification PathwaySpontaneous ReversionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.