Oxidative stress and the prion protein in transmissible spongiform encephalopathies

Protein aggregation in bacteria: the thin boundary between functionality and toxicity

“…In bacterial cells, calcium ions are involved in the maintenance of cell structure, motility, transport and cell differentiation processes such as sporulation, heterocyst formation and fruiting body development (Herbaud et al, 1998). There are a wide range of data published on cellular responses to the intracellular redox status and free Ca 2+ levels in cells exposed to toxic aggregates (Milhavet & Lehmann, 2002). Changes have been observed consisting of a sharp increase in the quantity of reactive oxygen species, reactive nitrogen species, lipid peroxidation, deregulation of NO metabolism, protein nitrosylation and upregulation of haem oxygenase-1, a specific marker of oxidative stress (Choi et al, 2000;Guentchev et al, 2000;Hyun et al, 2002).…”

Cellular pathogenesis in prion diseases

“…It is therefore easy to imagine that loss of these functions could directly increase susceptibility to oxidative stress and result in cell death. This is exemplified by studies reporting an increased susceptibility of PrP knock-out neuronal cells to oxidative stress [80]. Moreover, PrP exerts an anti-apoptotic function via its anti-Bax activity.…”

“…Conversion of PrP C into PrP Sc could alter this function and result in the loss of anti-oxidant defences [100]. In addition as abnormal protein accumulates in the injured brain, there is an increase of oxidative substances such as reactive oxygen species (ROS) (for review see [80]). The loss of the anti-oxidant defences will increase cell susceptibility to oxidative substances and therefore promotes cell death.…”

Impact of methionine oxidation as an initial event on the pathway of human prion protein conversion

“…7,8 In proteins, particularly the sulfur containing side chains of cysteine (Cys) and methionine (Met) residues are most sensitive to oxidation by highly reactive oxygen species (ROS). 9 Copper redox cycling in the presence of physiological reductants, e.g., ascorbate, is the main source of ROS formation in the organisms, converting the moderate hydrophobic thioether side chain of methionines into a more hydrophilic sulfoxide that frequently affects the structural integrity of proteins.…”