Cell culture density affects the susceptibility of human glioma cells to β‐ODAP toxicity

β‐ODAP is a neurotoxin that is found in the seeds of the grass pea, Lathyrus satvius, and is reported to cause neurolathyrism. The mechanism by which β‐OD AP causes neurolathyrism is not well understood, but it has been shown to be a transportable inhibitor of the transporter, system x c − . System x c − is involved in the exchange of cystine and glutamate across the plasma membrane in order to supply the cell with the cysteine necessary to maintain cellular glutathione levels. Previous studies in our lab have shown that system x c − cell surface expression is regulated by the redox state of the cell and cell culture density. In this study, we used β‐ODAP to inhibit cystine uptake by system x c − in order to reduce cellular glutathione levels in cultured glioma cells, and we subsequently examined the susceptibility of these cells to oxidative cell death. We have shown that effect of β‐ODAP on cellular glutathione levels and susceptibility to oxidative cell death is also dependent on cell culture density, with confluent cultures demonstrating an increased capacity to maintain cellular gluathione levels and resist oxidative cell death compared to non‐confluent cells. We hypothesize that the observed differences in susceptibility of confluent and non‐confluent cultures to β‐ODAP are a result of reduced capacity of non‐confluent cells to increase cell surface expression of System x c − when the oxidative load of the cell is increased.