The Relationship between H2o2-associated Oxidative Stress and Vhl Protein

Many environmental factors, including hypoxia, can induce oxidative stress. Cells that are subjected to oxidative stress often generate reactive oxygen species (ROS), which include hydrogen peroxide (H2O2). Familial von Hippel-Lindau (VHL) disease develops in individuals who are born heterotrophic for the wild-typeVHL gene, and who subsequently lose the remaining wt-VHL allele due to mutation. Excessive, unregulated quantities of ROS are known to damage cellular macromolecules, including proteins, lipids, and nucleic acids. We are currently examining the oxidative status of cells that express (wt-VHL) or lack (mut-VHL) the VHL protein, as a decrease in a cell’s ability to maintain “oxidative homeostasis” may be related to DNA damage, and expression of VHL pathology. Results from experiments in which H2O2 production was measured in VHL(+) or VHL(-) cell lines, under either normoxic (21% O2) or hypoxic (1% O2) conditions, revealed higher, basal amounts of H2O2 in VHL(-) cells in normoxic conditions, as contrasted to VHL(+) cells. Hypoxia reduced production of H2O2 in both VHL(+) and VHL(-) cell lines. Confirmation of these results using a different method of H2O2 measurement and the evaluation of expression levels of enzymes involved in the oxidative stress pathway continue.