Prion Protein-Deficient Cells Show Altered Response to Oxidative Stress Due to Decreased SOD-1 Activity

Brown, David R.; Schulz‐Schaeffer, Walter; Schmidt, Bernhard; Kretzschmar, Hans A.

doi:10.1006/exnr.1997.6505

Cited by 416 publications

(346 citation statements)

References 37 publications

Supporting

Mentioning

318

Contrasting

Unclassified

Order By: Relevance

“…Studies in vivo, on the brains of PrP-null mouse lines, and in vitro, on primary neuronal cultures derived from these lines, have revealed a reduction in the activities of the antioxidant enzymes SOD1 and glutathione reductase in the absence of PrP. 46,47 Additionally, cultured PrP-deficient neurons were found to have increased susceptibility to hydrogen peroxide or oxygenfree radical toxicity. Furthermore, we have found evidence of oxidative stress-induced damage in the form of increased levels of protein oxidation and lipid peroxidation in the brains of the Dpl-expressing ataxic, Rcm0, line as compared with the nonataxic, Npu, line.…”

Section: Discussionmentioning

confidence: 99%

Male Infertility and DNA Damage in Doppel Knockout and Prion Protein/Doppel Double-Knockout Mice

Paisley

Banks

Selfridge

et al. 2004

The American Journal of Pathology

View full text Add to dashboard Cite

The prion protein (PrP) and Doppel (Dpl) have many structural and biochemical properties in common, leading to the suggestion that the lack of an obvious phenotype in PrP-deficient mice maybe because of compensation by Dpl. To test this hypothesis and also investigate the function of Dpl we have generated Prnd ؊/؊ and Prnp ؊/؊ /Prnd ؊/؊ mouse lines. Both develop normally and display an identical male sterility phenotype that differs from that reported for another Prnd ؊/؊ mouse line. Sperm from both our mutant lines were present at normal concentrations, had normal motility, and no morphological abnormalities. Despite only rarely fertilizing oocytes in vivo, because of an inability to perform the acrosome reaction, mutant sperm were capable of fertilization in vitro, albeit at reduced rates compared to wild type. Elevated levels of oxidative DNA damage were found in both types of mutant sperm and resulting embryos failed at an early stage. Therefore we found no evidence that Dpl compensates for the loss of PrP function in mutant mouse lines, but it does have an important anti-oxidant function necessary for sperm integrity and male fertility.

show abstract

Section: Discussionmentioning

confidence: 99%

Male Infertility and DNA Damage in Doppel Knockout and Prion Protein/Doppel Double-Knockout Mice

Paisley

Banks

Selfridge

et al. 2004

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…However, other studies have not reproduced these results, since subcellular fractions of WT and PrP c knockout mice show equal Cu 2+ level and Cu/Zn SOD and CitC oxidase activity (Waggoner et al, 2000). Far from these discrepancies, in vitro cerebellar neuron cultures revealed that PrP c modulates oxidative stress through regulating Superoxide Dismutase-1 (SOD-1) activity in a Copper-dependent manner (Brown et al, 1997b;Sorenson, 2001). …”

Section: Prp C Andmentioning

confidence: 99%

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

Nicolas

Gavı́n

Rı́o

2009

Brain Research Reviews

View full text Add to dashboard Cite

show abstract

“…Supporting the latter function, the region between codons 50 and 91, comprising one nona-and four octapeptide repeats, specifically binds copper (4). The fact that copper is a key redox transition metal and the observation that PrP C regulates the activity of the Cu 2ϩ /Zn 2ϩ -superoxide dismutase (5)(6)(7)(8)(9) suggest that PrP C plays a role in redox balance.…”

mentioning

confidence: 99%

Prion Protein Glycosylation Is Sensitive to Redox Change

Capellari

Zaidi

Urig

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

The conversion of soluble prion protein into an insoluble, pathogenic, protease-resistant isoform is a key event in the development of prion diseases. Although the mechanism by which the conversion engenders a pathogenic event is unclear, there is increasing evidence to suggest that this may depend on the function of the prion protein in preventing oxidative damage. Therefore, in this study, we assessed the interrelationship between redox-sensitive cysteine, glycosylation, and prion metabolism. Cells were treated with a thioreductant, dithiothreitol, to assess the effect of the cellular oxidation state on the synthesis of the prion protein. This change in redox balance affected the glycosylation of the prion protein, resulting in the sole production of glycosylated forms. The role of the single disulfide bridge in mediating this effect within the prion protein was confirmed by mutating the cysteine residues involved in its formation. These data suggest that conditions that increase the rate of formation of the disulfide bridge favor formation of the unglycosylated prion protein. Thus, since the presence of glycans on the prion protein is protective against its pathogenic conversion, a change in the redox status of the cell would increase the risk of developing a prion disease by favoring the production of the unglycosylated form.

show abstract

Prion Protein-Deficient Cells Show Altered Response to Oxidative Stress Due to Decreased SOD-1 Activity

Cited by 416 publications

References 37 publications

Male Infertility and DNA Damage in Doppel Knockout and Prion Protein/Doppel Double-Knockout Mice

Male Infertility and DNA Damage in Doppel Knockout and Prion Protein/Doppel Double-Knockout Mice

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

Prion Protein Glycosylation Is Sensitive to Redox Change

Contact Info

Product

Resources

About