Changes in GDPase/UDPase enzymatic activity in response to oxidative stress in four Candida species.

The terminal processing of proteins and lipids occurs in the Golgi apparatus and involves the transport of sugar nucleotides into the Golgi lumen by specific carriers and the accumulation of nucleoside diphosphates (NDPs) as a result of oligosaccharide-protein glycosyltransferase activity. NDPs are converted into the corresponding nucleoside monophosphates (NMPs) by nucleoside diphosphatases (NDPases), thus relieving inhibition of sugar transferases. In addition, NMPs are then exchanged for equimolecular amounts of cytosolic sugar nucleotides by antiport transport systems. NDPases, commonly GDPase and UDPase, thus play a critical role in glycoprotein maturation and may influence fungal pathogenesis, morphogenesis, and cell wall properties. Interest of this laboratory has recently focused on the effect of reactive oxygen species (ROS) on enzymes involved in detoxification of these oxidants and on the metabolism of biomolecules such as lipids, nucleic acids, and proteins in human pathogenic Candida species. We therefore consider it important to extend these studies to determine how GDPase and UDPase are affected after exposure of cells to oxidants such as menadione, a superoxide (O2 (•-))-generator, and H2O2. Results indicate that activity of both enzymes decrease in response to these agents suggesting that ROS may also affect other critical cell functions such as protein glycosylation.