“…PrP C plays an important role in anti-oxidative defense, and its deficiency increases susceptibility to oxidative stress [84]. Glutathione peroxidase is one of the major antioxidant enzymes in the detoxification of hydrogen peroxide [85], [86]. The brain is considered to have lower GPx-1 activity compared with other tissues [85].…”
Section: Discussionmentioning
confidence: 99%
“…Glutathione peroxidase is one of the major antioxidant enzymes in the detoxification of hydrogen peroxide [85], [86]. The brain is considered to have lower GPx-1 activity compared with other tissues [85]. This enzyme is abundant in activated microglia and is present at low levels in most neurons [85].…”
Section: Discussionmentioning
confidence: 99%
“…The brain is considered to have lower GPx-1 activity compared with other tissues [85]. This enzyme is abundant in activated microglia and is present at low levels in most neurons [85]. In vitro studies have indicated that the lack of GPx1 enhances the toxicity of the amyloid beta-peptide [87].…”
The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed.
“…PrP C plays an important role in anti-oxidative defense, and its deficiency increases susceptibility to oxidative stress [84]. Glutathione peroxidase is one of the major antioxidant enzymes in the detoxification of hydrogen peroxide [85], [86]. The brain is considered to have lower GPx-1 activity compared with other tissues [85].…”
Section: Discussionmentioning
confidence: 99%
“…Glutathione peroxidase is one of the major antioxidant enzymes in the detoxification of hydrogen peroxide [85], [86]. The brain is considered to have lower GPx-1 activity compared with other tissues [85]. This enzyme is abundant in activated microglia and is present at low levels in most neurons [85].…”
Section: Discussionmentioning
confidence: 99%
“…The brain is considered to have lower GPx-1 activity compared with other tissues [85]. This enzyme is abundant in activated microglia and is present at low levels in most neurons [85]. In vitro studies have indicated that the lack of GPx1 enhances the toxicity of the amyloid beta-peptide [87].…”
The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed.
“…Furthermore, marmoset GPx‐1 and GPx‐4 (Fig. 1) contain tryptophan (in GPx‐1 Trp161; in GPx‐4 Trp163) and glutamine residues (in GPx‐1 Gln83; in GPx‐4 Gln108) in homologous positions supporting the presence of almost identical catalytic centers in all mammals [2, 14–16, 31, 32]. It is known that these three amino acids compose a specific triad through hydrogen bonds that provide stabilization of Se in the active center.…”
Section: Discussionmentioning
confidence: 99%
“…Additionally, four arginine residues and one lysine residue compose the electrostatic architecture of the enzyme and direct the substrate toward the catalytic center [1]. These amino acids were found at similar positions in the marmoset GPx‐1 (Arg53, 99, 180 and 181, and Lys 87) and in other primates [15, 16].…”
These findings will be of value for studies designed to assess the role of glutathione peroxidases in non-human primate models for a variety of diseases in which increased oxidative stress has been implicated.
Glutathione peroxidase (GPx-1) is regarded as one of the mammalian cell's main antioxidant enzymes inactivating hydrogen peroxide and protecting against oxidative stress. Using control, Parkinson's disease (PD), and dementia with Lewy bodies tissue (DLB) we have shown that GPx-1 is a 21-kD protein under reducing conditions in all tissues examined but is not in high abundance in human brain. Using immunohistochemistry we have mapped the cellular distribution of GPx-1 and have shown it to be in highest levels in microglia and with lower levels in neurons. Only a trace amount was detectable in astrocytes using immunofluorescence and GPx-1 was not detectable in oligodendrocytes. GPx-1 positive microglia were hypertrophied and more abundant in PD and DLB tissues and were seen to be making multiple contacts with neurons. In some cases neurons containing Lewy bodies were surrounded by microglia. Unstructured Lewy bodies were enveloped with a layer of GPx-1 that was partially colocalized with alpha-synuclein whereas concentric Lewy bodies had discrete deposits of GPx-1 around the periphery which appeared to be involved in the degradation of the Lewy bodies. These results suggest that abnormal alpha-synuclein as found in Lewy bodies produce hydrogen peroxide and these neurons are capable of directing antioxidant enzymes to regions of oxidative stress. These results also suggest that GPx-1 positive microglia are involved in neuroprotection in PD and DLB and that GPx-1 is an important antioxidant enzyme in neuronal defences.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.