Journal article
Acute exposure to prion infection induces transient oxidative stress progressing to be cumulatively deleterious with chronic propagation in vitro
CL Haigh, AR McGlade, V Lewis, CL Masters, VA Lawson, SJ Collins
Free Radical Biology and Medicine | Published : 2011
Abstract
Neuronal loss is a pathological feature of prion diseases for which increased reactive oxygen species (ROS) and consequent oxidative stress is one proposed mechanism. The processes underlying ROS production in prion disease and the precise relationship to misfolding of the prion protein remain obscure. Using cell culture models of prion infection we found that cells demonstrate a rapid, prion protein (PrP) dependent, increase in intracellular ROS following exposure to infectious inoculum. ROS production correlated with internalisation and increased intracellular protease resistant PrP (PrP Res). The ROS increase was predominantly lysosomal in origin but not sustained, with cells adapting wit..
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Grants
Awarded by Brain Foundation
Funding Acknowledgements
The authors would like to acknowledge A/Prof AF Hill for the kind gift of the pIRES vector containing the PrP open reading frames and Dr Simon Drew for the SR-VAD-FMK reagent. The OBL-21 cell line used in this study were a kind gift of Dr Michael Oldstone, The Scripps Research Institute, La Jolla, California, USA. This study was funded by a Brain Foundation research grant. SJC is supported by an NH&MRC Practitioner Fellowship #400183 and an NH&MRC programme grant #400202. VL is supported by an NH&MRC Training (Postdoctoral) Fellowship #567123. VAL is supported by a University of Melbourne CR Roper fellowship.