Lipopolysaccharide induced conversion of recombinant prion protein

Saleem, Fahad; Bjorndahl, Trent C.; Ladner, Carol L.; Perez-Pineiro, Rolando; Ametaj, Burim N.; Wishart, David S.

doi:10.4161/pri.28939

Cited by 29 publications

(39 citation statements)

References 52 publications

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“…33 Our data showed that this gene was also upregulated. Moreover, Mapk14, Mapk8, and Jun all of which are part of the JNK pathway and Irak1, and Nfkbia which are involved in apoptosis were up-regulated by moPrP M C LPS M. Previously we showed that LPS interacts with moPrP and converts it into a b-rich aggregated isoform that is resistant to proteinase K. 15 We speculate that aggregates of moPrP and LPS were probably endocytosed by the colon epithelial cells and potentially induced overexpression of JNK-signaling pathway. JNK activation leads to phosphorylation of transcription factors controlling the apoptotic process, 34 thereby resulting in cell death.…”

mentioning

confidence: 89%

“…10,11 Also, an increase in PrP C expression has been demonstrated during gastric infection by Helicobacter pylori, 12 bacterial kidney infection, 13 and inflammation of the skin. 14 In a previous study we demonstrated that LPS from Escherichia coli 0111:B4 interacts with recombinant Syrian hamster PrP (shPrP) and converts the a-helix-rich protein into a b-sheet rich isoform that forms amyloid-like fibrils resistant to proteinase K. 15 Furthermore this conversion occurs under physiological conditions. Implications of interaction of prion protein with LPS are not known.…”

Section: Introductionmentioning

confidence: 99%

“…The interaction between LPS and moPrP in the colon is of pathophysiological relevance because previously we reported that LPS interacts with mouse, bovine, and Syrian hamster prions and converts them instantly from a-helix-rich proteins into b-sheet rich isoforms that form amyloid-like fibrils resistant to proteinase K. 15 This conversion occurs under physiological conditions. Addition of moPrP and LPS to the mucosal compartment (PrP M C LPS M) of the Ussing chamber was associated with modified expression of 12 genes, where 11 of them were upregulated and only (Card9) was down-regulated ( Table 1).…”

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confidence: 98%

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Recombinant mouse prion protein alone or in combination with lipopolysaccharide alters expression of innate immunity genes in the colon of mice

Dervishi

Lam

Dunn

et al. 2015

Prion

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ABSTRACT. The objectives of this study were to test whether recombinant mouse (mo)PrP alone or in combination with LPS or under simulated endotoxemia would affect expression of genes related to host inflammatory and antimicrobial responses. To test our hypotheses colon tissues were collected from 16 male mice (FVB/N strain) and mounted in an Ussing chamber. Application of moPrP to the mucosal side of the colon affected genes related to TLR-and NLR-signaling and antimicrobial responses. When LPS was added on the mucosal side of the colon, genes related to TLR, Nlrp3 inflammasome, and iron transport proteins were over-expressed. Addition of LPS to the serosal side of the colon up-regulated genes related to TLR-and NLR-signaling, Nlrp3 inflammasome, and a chemokine. Treatment with both moPrP and LPS to the mucosal side of the colon upregulated genes associated with TLR, downstream signal transduction (DST), inflammatory response, attraction of dendritic cells to the site of inflammation, and the JNK-apoptosis pathway. Administration of moPrP to the mucosal side and LPS to the serosal side of the colon affected genes related to TLR-and NLRsignaling, DST, apoptosis, inflammatory response, cytokines, chemokines, and antimicrobial peptides. Overall this study suggests a potential role for moPrP as an endogenous 'danger signal' associated with activation of colon genes related to innate immunity and antibacterial responses.

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confidence: 89%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 98%

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Recombinant mouse prion protein alone or in combination with lipopolysaccharide alters expression of innate immunity genes in the colon of mice

Dervishi

Lam

Dunn

et al. 2015

Prion

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“…While the combined actions of host and microbiota-derived proteolytic enzymes may contribute to the partial digestion of certain prion isolates in the gut lumen, detectable levels of infectious prions can survive these processes and are secreted in the faeces of BSE-, CWD-and scrapie-infected hosts (Krüger et al, 2009;Maluquer de Motes et al, 2008;Safar et al, 2008;Tamgüney et al, 2009), and can survive passage through the gastrointestinal tracts of coyotes (Canis latrans) (Nichols et al, 2015) and crows (VerCauteren et al, 2012). One study has also proposed that bacterial components, such as LPS, may potentially enhance the abnormal folding of recombinant PrP (Saleem et al, 2014).…”

Section: Direct Effects Of the Gut Microbiota On Prionsmentioning

confidence: 99%

The influence of the commensal and pathogenic gut microbiota on prion disease pathogenesis

Donaldson

Mabbott

2016

Journal of General Virology

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“…In these methods, the conversion of recPrP c to PrP β is performed through the addition of denaturants and cofactors such as detergents 5 , urea 6 , copper ions 7 , acid 6 , RNA 8,9 , DNA 10,11 , glycosaminoglycans 12 , lipids 13 and lipopolysaccharides 14 . However, conformational change to a β-sheet rich structure is not sufficient to create infectious prions (PrP Sc ).…”

Section: Introductionmentioning

confidence: 99%

Role of polysaccharide and lipid in lipopolysaccharide induced prion protein conversion

Ladner-Keay

LeVatte

Wishart

2016

Prion

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Conversion of native cellular prion protein (PrPc) from an α-helical structure to a toxic and infectious β-sheet structure (PrPSc) is a critical step in the development of prion disease. There are some indications that the formation of PrPSc is preceded by a β-sheet rich PrP (PrPβ) form which is non-infectious, but is an intermediate in the formation of infectious PrPSc. Furthermore the presence of lipid cofactors is thought to be critical in the formation of both intermediate-PrPβ and lethal, infectious PrPSc. We previously discovered that the endotoxin, lipopolysaccharide (LPS), interacts with recombinant PrPc and induces rapid conformational change to a β-sheet rich structure. This LPS induced PrPβ structure exhibits PrPSc-like features including proteinase K (PK) resistance and the capacity to form large oligomers and rod-like fibrils. LPS is a large, complex molecule with lipid, polysaccharide, 2-keto-3-deoxyoctonate (Kdo) and glucosamine components. To learn more about which LPS chemical constituents are critical for binding PrPc and inducing β-sheet conversion we systematically investigated which chemical components of LPS either bind or induce PrP conversion to PrPβ. We analyzed this PrP conversion using resolution enhanced native acidic gel electrophoresis (RENAGE), tryptophan fluorescence, circular dichroism, electron microscopy and PK resistance. Our results indicate that a minimal version of LPS (called detoxified and partially de-acylated LPS or dLPS) containing a portion of the polysaccharide and a portion of the lipid component is sufficient for PrP conversion. Lipid components, alone, and saccharide components, alone, are insufficient for conversion.

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Lipopolysaccharide induced conversion of recombinant prion protein

Cited by 29 publications

References 52 publications

Recombinant mouse prion protein alone or in combination with lipopolysaccharide alters expression of innate immunity genes in the colon of mice

Recombinant mouse prion protein alone or in combination with lipopolysaccharide alters expression of innate immunity genes in the colon of mice

The influence of the commensal and pathogenic gut microbiota on prion disease pathogenesis

Role of polysaccharide and lipid in lipopolysaccharide induced prion protein conversion

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