• 제목/요약/키워드: Scrapie PrP

검색결과 13건 처리시간 0.026초

Mycosporine-like amino acids (MAAs) 처리에 따른 배양세포 내 스크래피 프리온 단백질의 형성증가 (Enhanced Formation of Scrapie Prion Protein in Cultured Cells by Treatment with Mycosporine-like Amino Acids (MAAs))

  • 이지현;모상현;류종석;김대환
    • 한국미생물·생명공학회지
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    • 제43권2호
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    • pp.91-96
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    • 2015
  • Prion은 양의 scrapie, 소의 bovine spongiform encephalopathy와 사람의 CJD와 같은 다양한 신경 퇴행성 질환을 유발시키는 단백질 병원체이다. 정상 prion 단백질인 PrPC가 병원성 PrPSc로 바뀌는 과정에 대해서는 많은 연구가 진행되었고, PrPSc로의 단백질 구조 변화가 다양한 환경적 요소에 의해서 영향 받는 것으로 추측된다. 바다조류로부터 분리된 MAAs는 다양한 스트레스 환경에서 조류를 보호해주는 것으로 알려져 있다. 이와 같은 사실에 기초하여 mycosporineglycine, porphyra-334와 shinorine 3종의 MAAs로 처리한 prion 감염 신경세포 주에서 prion 단백질 축적의 변화를 평가하였다. PK 저항성을 갖는 PrPSc를 western blot 방법으로 확인한 결과, MAA에 의해서 PrPSc 단백질의 증식을 관찰하였다.

Physiology of Cellular Prion Proteins in Reproduction

  • Zeljko M. Svedruzic;Chongsuk Ryou;Donchan Choi;Sung-Ho Lee;Yong-Pil Cheon
    • 한국발생생물학회지:발생과생식
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    • 제28권2호
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    • pp.29-36
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    • 2024
  • Cellular prion protein (PrPC) encoded at Prnp gene is well-known to form a misfolded isoform, termed scrapie PrP (PrPSC) that cause transmissible degenerative diseases in central nervous system. The physiological role of PrPC has been proposed by many studies, showing that PrPC interacts with various intracellular, membrane, and extracellular molecules including mitochondrial inner membrane as a scaffold. PrPC is expressed in most cell types including reproductive organs. Numerous studies using PrPC knockout rodent models found no obvious phenotypic changes, in particular the clear phenotypes in development and reproduction have not demonstrated in these knockout models. However, various roles of PrPC have been evaluated at the cellular levels. In this review, we summarized the known roles of PrPC in various cell types and tissues with a special emphasis on those involved in reproduction.

Prion Protein Genotypes in Pakistani Goats

  • Babar, M.E.;Nawaz, M.;Nasim, A.;Abdullah, M.;Imran, M.;Jabeen, R.;Chatha, S.A.;Haq, A.U.;Nawaz, A.;Mustafa, H.;Nadeem, A.
    • Asian-Australasian Journal of Animal Sciences
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    • 제21권7호
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    • pp.936-940
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    • 2008
  • The PCR-amplified prion protein (PrP) gene was sequenced to determine the frequency of scrapie-associated as well as novel PrP genotypes in 72 healthy goats representing five breeds. A total of six genotypes were detected, resulting from the three reported 143 (H/R), 154 (R/H) and 240 (S/P) and the two novel 39 (S/R) and 185 (I/F) amino acid polymorphisms. Of the four silent mutations 42 (a$\rightarrow$g), 138 (c$\rightarrow$t), 231 (c$\rightarrow$a) and 237 (g$\rightarrow$c) detected in this study, 237 (g$\rightarrow$c) is novel. A genotype (SIP/RFP) harboring three amino acid polymorphisms 39 (S/R), 185 (I/F) and 240 (S/P) was found in few goats. Although both scrapie-associated genotypes with 143 (H/R) and 154 (R/H) polymorphisms and others with 39 (S/R), 185 (I/F) and 240 (S/P) polymorphisms were present in the studied Pakistani goats, their frequency was lower than that of the wild-type genotype SHRIS/SHRIS (34.7%). These results emphasize the need for further sequencing of the PrP gene in a large number of goats representing the five studied breeds, so that overall PrP variability can be assessed in these breeds in research addressing future concerns about scrapie.

Effect of Polylysine on Scrapie Prion Protein Propagation in Spleen during Asymptomatic Stage of Experimental Prion Disease in Mice

  • Titlow, William B.;Waqas, Muhammad;Lee, Jihyun;Cho, Jae Youl;Lee, Sang Yeol;Kim, Dae-Hwan;Ryou, Chongsuk
    • Journal of Microbiology and Biotechnology
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    • 제26권9호
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    • pp.1657-1660
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    • 2016
  • Prion diseases are incurable neurodegenerative disorders. Our previous study demonstrated that polylysine was effective in prolonging the incubation period in a rodent model and in alleviating the scrapie prion protein (PrPSc) burden in the brain at the terminal stage of the disease. Here, we report that intraperitoneal administration of polylysine suppresses the accumulation of prions in the spleen during the early stages of the disease. This study supports the congruence of PrPSc inhibition by polylysine in both the spleen and brain.

스크래피에 감염된 마우스의 뇌 및 간조직에서의 DNA Methylation (DNA Methylation in Brain and Liver Tissues of Mice Infected with Scrapie Agent)

  • 최은경;;;;김용선
    • 대한바이러스학회지
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    • 제28권2호
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    • pp.183-192
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    • 1998
  • DNA methylation degree in the several murine brain and liver genes of different ages and after scrapie infection have been examined by using methylation-sensitive restriction endonuclease digestion. We found that the methylation of c-fos and c-myc in the brain and liver was increased during the late fetal to one month postnatal developmental periods. However, those of the SGP-2, $S100{\beta}$, APP950, PrP, and APLP1 genes were decreased at the same periods. The comparison of the DNA methylation patterns between scrapie infected brains and controls demonstrated there is no significant difference in methylation degree of scrapie-infected brains. These observations indicate that DNA methylation might be importantly related to the aging process. The scrapie-infected murine brain was not significantly developed more senescent than the same age-controls did.

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Generation of ovine recombinant prion protein (25-232): Characterisation via anti-PrP monoclonal antibodies and CD spectroscopy

  • Yang, Su-Jeong;Thackray, Alana;Bujdoso, Raymond
    • 한국동물위생학회지
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    • 제28권4호
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    • pp.393-405
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    • 2005
  • In prion pathogenesis, the structural conversion of the cellular prion protein $(PrP^c)$ to its abnormal isomer $(PrP^{Sc})$ is believed to be a major event. The susceptibility or resistance to natural sheep scrapie is associated with polymorphisms of host PrP gene (PRNP) at amino acid residues 136, to a lesser extent 154. The 112 residue in ovine PrP displays a natural polymorphism, Methionine to Threonine, which has not been thoroughly investigated. However the cell-free conversion assay showed that ARQ with Thr112 $(T_{112}ARQ)^{1)}$ presents lower convertibility to $PrP^{Sc}$than wild type ARQ $(M_{112}ARQ)$ [1] In this study we generated ovine recombinant PrPs of 112 allelic variants by metal chelate affinity chromatography and cation exchange chromatography. The final purity of the ovine PrP ARQ was more than $95\%$. These variants showed similar immunoreactivity against anti-PrP monoclonal antibodies in Western blot and ELISA. The refolded $M_{112}ARQ$ and $M_{112}ARQ$ presented the secondary structural content to similar extent via CD spectroscopy analysis. The inherited structural features of $M_{112}ARQ$ and $M_{112}ARQ$ under the different biophysical conditions are in the middle of investigation.

The role of cellular prion protein in immune system

  • Seunghwa Cha;Mi-Yeon Kim
    • BMB Reports
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    • 제56권12호
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    • pp.645-650
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    • 2023
  • Numerous studies have investigated the cellular prion protein (PrPC) since its discovery. These investigations have explained that its structure is predominantly composed of alpha helices and short beta sheet segments, and when its abnormal scrapie isoform (PrPSc) is infected, PrPSc transforms the PrPC, leading to prion diseases, including Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. Given its ubiquitous distribution across a variety of cellular types, the PrPC manifests a diverse range of biological functions, including cell-cell adhesion, neuroprotection, signalings, and oxidative stress response. PrPC is also expressed in immune tissues, and its functions in these tissues include the activation of immune cells and the formation of secondary lymphoid tissues, such as the spleen and lymph nodes. Moreover, high expression of PrPC in immune cells plays a crucial role in the pathogenesis of prion diseases. In addition, it affects inflammation and the development and progression of cancer via various mechanisms. In this review, we discuss the studies on the role of PrPC from various immunological perspectives.

Solution Structure of a Prion Protein: Implications for Infectivity

  • He Liu;Jones, Shauna-Farr;Nikolai Ulyanov;Manuel Llinas;Susan Marqusee;Fred E. Cohen;Stanley B. Prusiner;Thomas L. James
    • 한국자기공명학회논문지
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    • 제2권2호
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    • pp.85-105
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    • 1998
  • Prions cause neurodegenerative diseases in animals and humans. The scrapie prion protein (PrPSc) is the major-possibly only-component of the infectious prion and is generated from the cellular isoform (PrPC) by a conformational change. Limited proteolysis of PrPSc produces an polypeptide comprised primarily of residues 90 to 231, which retains infectivity. The three-dimensional structure of rPrP(90-231), a recombinant protein resembling PrPC with the Syrian hamster (SHa) sequence, was solved using multidimensional NMR. Low-resolution structures of rPrP(90-231), synthetic peptides up to 56 residues, a longer (29-231, full-length) protein with SHa sequence, and a short here further structure refinement of rPrP(90-231) and dynamic features of the protein. Consideration of these features in the context of published data suggests regions of conformational heterogeneity, structural elements involved in the PrPC\longrightarrowPrPSc transformation, and possible structural features related to a species barrier to transmission of prion diseases.

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Prion Protein Does Not Interfere with SNARE Complex Formation and Membrane Fusion

  • Yang, Yoo-Soo;Shin, Jae-Il;Shin, Jae-Yoon;Oh, Jung-Mi;Lee, Sang-Ho;Yang, Joo-Sung;Kweon, Dae-Hyuk
    • Food Science and Biotechnology
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    • 제18권3호
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    • pp.782-787
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    • 2009
  • In prion disease, spongiform neurodegeneration is preceded by earlier synaptic dysfunction. There is evidence that soluble N-ethylmaleimide sensitive factor attachment receptor (SNARE) complex formation is reduced in scrapie-infected in vivo models, which might explain this synaptic dysfunction because SNARE complex plays a crucial role in neuroexocytosis. In the present study, however, it is shown that prion protein (PrP) does not interfere with SNARE complex formation of 3 SNARE proteins: syntaxin 1a, SNAP-25, and synaptobrevin. Sodium dodecyl sulfate-resistant complex formation, SNAREdriven membrane fusion, and neuroexocytosis of PC12 cells were not altered by PrP. Thus, PrP does not alter synaptic function by directly interfering with SNARE complex formation.

국내, 외 광우병의 발생 현황과 대응 방안 (The current status and control measures of BSE in the worldwide)

  • 유한상
    • 한국환경농학회:학술대회논문집
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    • 한국환경농학회 2009년도 정기총회 및 국제심포지엄
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    • pp.273-282
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    • 2009
  • The transmissible spongiform encephalopathies (TSEs) disease group are fatal neurodegenerative disorders affecting a wide range of hosts. The group includes kuru and Creutzfeldt-Jakob disease (CJD) in humans, scrapie in sheep and goats and Bovine spongiform encephalopathy (BSE) in cattle. The exact nature of the infectious agent involved in the transmission of these diseases remains controversial. However, a central event in their pathogenesis is the accumulation in infected tissues of an abnormal form of a host-encoded protein, the prion protein (PrP). Whereas the normal cellular protein is fully sensitive to protease ($PrP^{sen}$), the disease-associated prion protein ($PrP^d$) is only partly degraded ($PrP^{res}$), its amino-terminal end being removed. BSE was first reported in the mid-80s in the UK. Ten years later, a new form of human prion disease, variant CJD (vCJD) developed in the wake of the BSE epidemic, and there is now strong scientific evidence that vCJD was initiated by the exposure of humans to BSE-infected tissues, thus indicating a zoonotic disease. However, the ban on the feeding of animal-derived proteins to ruminants, and the apparent lack of vertical transmission of BSE, have led to a decline in the incidence of the disease within cattle herd and therefore, an assumed decreased risk for human contacting vCJD. The origin of the original case(s) of BSE still remains an enigma even though three hypotheses have been raised. Hypotheses are i) sheep- or goat-derived scrapie-infected tissues included in meat and bone meal fed to cattle, ii) a previously undetected sporadic or genetic bovine TSE contaminating cattle feed or iii) originating from a human TSE through animal feed contaminated with human remains. A host cellular membrane protein ($PrP^C$), which is abundant in central nervous system tissue, appear to be conformationally altered in the diseased host into a prion protein ($PrP^{Sc}$). This $PrP^{Sc}$ is detergent insoluble and partially protease-resistant ($PrP^{res}$). The term $PrP^{res}$ is normally used to describe the protein detected after protease treatment, in techniques such as Western immunoblotting, and enzyme-linked immunosorbant assay using fresh/frozen tissue. Immunohistochemistry may performed with formalin-fixed tissues. Also, clinical signs of the BSE are one of the major diagnostic indicators. Recently, atypical forms (known as H- and L-type) of BSE have appeared in several European countries, Japan, Canada and the United States. An unusual case was also reported in a miniature zebu. The atypical BSE fall into two groups based on the relative molecular mass (Mm) of the unglycosylated $PrP^{res}$ band relative to that of classical BSE, one of the higher Mm (H-type) and the other lower (L-type). Both types have been detected worldwide as rare cases in older animals, at a low prevalence consistent with the possibility of sporadic forms of prion diseases in cattle. This raises the unwelcome possibility that vCJD could increase in the human population. Now, active surveillance program against BSE is going on in Korea. In regional veterinary service lab, ELISA is applied to screen the BSE in slaughter and confirmatory tests by Western immunoblotting and immunohistochemisty are carried out if there are positive or suspect in the screening test. Also, the ruminant feed ban is rigorously enforced. Removal of specified risk materials such as brain and spinal cord from cattle is mandatory process at slaughter to prevent the infected material from entering the human food chain.

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