Oxidative stress evaluated for prion susceptibility
Disturbances in the normal redox state of a cell can cause toxic effects through the production of molecules such as free radicals that can damage all components of the cell, including proteins and DNA. In humans, oxidative stress is involved in many diseases, including atherosclerosis and Parkinson's disease and is implicated in the ageing process in general. Susceptibility to prion diseases including scrapie and Bovine spongiform encephalopathy (BSE) may also be linked to oxidative stress conditions. The normal prion protein, PrPc has an antioxidant activity that may enhance the survival of cells. This suggested that accumulation of the abnormal prion protein, PrPSc, may alter the redox or oxidative state of the cell. Partners in the OXPRION EU-funded project have investigated the role of oxidative stress on prion disease susceptibility. One of the steps in the research priocess was to impose an oxidative stress in mice using the organophosphate, dimethoate. In order to develop the model effectively, it was necessary to determine the level of dose that induced oxidative stress conditions. Extent of response of the relevant detoxifying enzyme systems in the liver were measured at different doses over varying times. These stress enzymes included catalase, and peroxidase GSHPx. An acute stress was measured in terms of the amounts of carbonyl groups in proteins. In this way, researchers were able to determine the dosage and duration of the treatment in order to induce the required state of oxidative stress in tissues. Further research could help to improve the basic understanding of the molecular mechanisms underlying susceptibility to prion-based diseases and contribute to the development of cellular tools to improve treatment.
