8 results on '"Hara,Hideyuki"'
Search Results
2. Melanin or a Melanin-Like Substance Interacts with the N-Terminal Portion of Prion Protein and Inhibits Abnormal Prion Protein Formation in Prion-Infected Cells
- Author
-
Hamanaka, Taichi, primary, Nishizawa, Keiko, additional, Sakasegawa, Yuji, additional, Oguma, Ayumi, additional, Teruya, Kenta, additional, Kurahashi, Hiroshi, additional, Hara, Hideyuki, additional, Sakaguchi, Suehiro, additional, and Doh-ura, Katsumi, additional
- Published
- 2017
- Full Text
- View/download PDF
3. Prion Protein Devoid of the Octapeptide Repeat Region Delays BSE Pathogenesis in Mice
- Author
-
Hara, Hideyuki, Miyata, Hironori, Das, Nandita Rani, Chida, Junji, Yoshimochi, Tatenobu, Uchiyama, Keiji, Watanabe, Hitomi, Kondoh, Gen, Yokoyama, Takashi, and Sakaguchi, Suehiro
- Subjects
Octapeptide repeat ,Prion protein ,animal diseases ,Bovine spongiform encephalopathy (BSE) ,mental disorders ,Prion ,nervous system diseases ,Scrapie - Abstract
Conformational conversion of the cellular isoform of prion protein PrPC, into the abnormally folded, amyloidogenic isoform, PrPSc, is a key pathogenic event in prion diseases including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrPC into PrPSc after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP-knockout background, designated Tg(PrPΔOR)/Prnp0/0 mice, did not reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPScΔOR in their brains. We show here that Tg(PrPΔOR)/Prnp0/0 mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPScΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrPC into PrPSc after infection with BSE prions. However, Tg(PrPΔOR)/Prnp0/0 mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPScΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/Prnp0/0 mice than PrPSc in control wild-type mice. Taken together, these results indicate that the OR region of PrPC could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions. IMPORTANCE Structure-function relationship studies of PrPC conformational conversion into PrPSc are worthwhile to understand the mechanism of the conversion of PrPC into PrPSc. We show here that, by inoculating the three different prion strains of RML, 22L and BSE prions, into Tg(PrP∆OR)/Prnp0/0 mice, the OR region could play a differential role in the conversion of PrPC into PrPSc after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPScΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPScΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrPC into PrPSc after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions.
- Published
- 2017
4. Mouse Prion Protein (PrP) Segment 100 to 104 Regulates Conversion of PrP C to PrP Sc in Prion-Infected Neuroblastoma Cells
- Author
-
Hara, Hideyuki, primary, Okemoto-Nakamura, Yuko, additional, Shinkai-Ouchi, Fumiko, additional, Hanada, Kentaro, additional, Yamakawa, Yoshio, additional, and Hagiwara, Ken'ichi, additional
- Published
- 2012
- Full Text
- View/download PDF
5. Mouse Prion Protein (PrP) Segment 100 to 104 Regulates Conversion of PrPC to PrPSc in Prion-Infected Neuroblastoma Cells.
- Author
-
Hara, Hideyuki, Okemoto-Nakamura, Yuko, Shinkai-Ouchi, Fumiko, Hanada, Kentaro, Yamakawa, Yoshio, and Hagiwara, Ken'ichi
- Subjects
- *
NEUROBLASTOMA , *PRIONS , *PROTEIN binding , *CANCER cells , *PRION diseases , *ALANINE , *LABORATORY mice - Abstract
Prion diseases are characterized by the replicative propagation of disease-associated forms of prion protein (PrPSc; PrP refers to prion protein). The propagation is believed to proceed via two steps; the initial binding of the normal form of PrP (PrPC) to PrPSc and the subsequent conversion of PrPC to PrPSc. We have explored the two-step model in prion-infected mouse neuroblastoma (ScN2a) cells by focusing on the mouse PrP (MoPrP) segment 92-GGTHNQWNKPSKPKTN-107, which is within a region previously suggested to be part of the binding interface or shown to differ in its accessibility to anti-PrP antibodies between PrPC and PrPSc. Exchanging the MoPrP segment with the corresponding chicken PrP segment (106-GGSYHNQKPWKPPKTN-121) revealed the necessity of MoPrP residues 99 to 104 for the chimeras to achieve the PrPSc state, while segment 95 to 98 was replaceable with the chicken sequence. An alanine substitution at position 100, 102, 103, or 104 of MoPrP gave rise to nonconvertible mutants that associated with MoPrPSc and interfered with the conversion of endogenous MoPrPC. The interference was not evoked by a chimera (designated MCM2) in which MoPrP segment 95 to 104 was changed to the chicken sequence, though MCM2 associated with MoPrPSc. Incubation of the cells with a synthetic peptide composed of MoPrP residues 93 to 107 or alanine-substituted cognates did not inhibit the conversion, whereas an anti-P8 antibody recognizing the above sequence in PrPC reduced the accumulation of PrPSc after 10 days of incubation of the cells. These results suggest the segment 100 to 104 of MoPrPC plays a key role in conversion after binding to MoPrPSc [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
6. Protective role of cytosolic prion protein against virus infection in prion-infected cells.
- Author
-
Hara H, Chida J, Batchuluun B, Takahashi E, Kido H, and Sakaguchi S
- Subjects
- Animals, Mice, Humans, Mitochondria metabolism, PrPSc Proteins metabolism, Prion Diseases metabolism, Prion Diseases pathology, Cell Line, Superoxide Dismutase metabolism, Prions metabolism, Prion Proteins metabolism, Necroptosis, Cytosol metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Inflammasomes metabolism, NF-kappa B metabolism, Reactive Oxygen Species metabolism
- Abstract
Production of the amyloidogenic prion protein, PrP
Sc , which forms infectious protein aggregates, or prions, is a key pathogenic event in prion diseases. Functional prion-like protein aggregations, such as the mitochondrial adaptor protein MAVS and the inflammasome component protein ASC, have been identified to play a protective role in viral infections in mammalian cells. In this study, to investigate if PrPSc could play a functional role against external stimuli, we infected prion-infected cells with a neurotropic influenza A virus strain, IAV/WSN. We found that prion-infected cells were highly resistant to IAV/WSN infection. In these cells, NF-κB nuclear translocation was disturbed; therefore, mitochondrial superoxide dismutase (mtSOD) expression was suppressed, and mitochondrial reactive oxygen species (mtROS) was increased. The elevated mtROS subsequently activated NLRP3 inflammasomes, leading to the suppression of IAV/WSN-induced necroptosis. We also found that prion-infected cells accumulated a portion of PrP molecules in the cytosol, and that the N-terminal potential nuclear translocation signal of PrP impeded NF-κB nuclear translocation. These results suggest that PrPSc might play a functional role in protection against viral infections by stimulating the NLRP3 inflammasome-dependent antivirus mechanism through the cytosolic PrP-mediated disturbance of NF-κB nuclear translocation, which leads to suppression of mtSOD expression and consequently upregulation of the NLRP3 inflammasome activator mtROS., Importance: Cytosolic PrP has been detected in prion-infected cells and suggested to be involved in the neurotoxicity of prions. Here, we also detected cytosolic PrP in prion-infected cells. We further found that the nuclear translocation of NF-κB was disturbed in prion-infected cells and that the N-terminal potential nuclear translocation signal of PrP expressed in the cytosol disturbed the nuclear translocation of NF-κB. Thus, the N-terminal nuclear translocation signal of cytosolic PrP might play a role in prion neurotoxicity. Prion-like protein aggregates in other protein misfolding disorders, including Alzheimer's disease were reported to play a protective role against various environmental stimuli. We here showed that prion-infected cells were partially resistant to IAV/WSN infection due to the cytosolic PrP-mediated disturbance of the nuclear translocation of NF-κB, which consequently activated NLRP3 inflammasomes after IAV/WSN infection. It is thus possible that prions could also play a protective role in viral infections., Competing Interests: The authors declare no conflict of interest.- Published
- 2024
- Full Text
- View/download PDF
7. Prion Protein Devoid of the Octapeptide Repeat Region Delays Bovine Spongiform Encephalopathy Pathogenesis in Mice.
- Author
-
Hara H, Miyata H, Das NR, Chida J, Yoshimochi T, Uchiyama K, Watanabe H, Kondoh G, Yokoyama T, and Sakaguchi S
- Subjects
- Animals, Brain pathology, Cattle, Encephalopathy, Bovine Spongiform prevention & control, Humans, Mice, Mice, Transgenic, Oligopeptides chemistry, Oligopeptides genetics, PrPC Proteins genetics, Prion Diseases prevention & control, Prions chemistry, Prions genetics, Sequence Deletion, Disease Susceptibility, Encephalopathy, Bovine Spongiform physiopathology, PrPC Proteins chemistry, PrPC Proteins physiology, Prion Diseases physiopathology, Prions pathogenicity
- Abstract
Conformational conversion of the cellular isoform of prion protein, PrP
C , into the abnormally folded, amyloidogenic isoform, PrPSc , is a key pathogenic event in prion diseases, including Creutzfeldt-Jakob disease in humans and scrapie and bovine spongiform encephalopathy (BSE) in animals. We previously reported that the octapeptide repeat (OR) region could be dispensable for converting PrPC into PrPSc after infection with RML prions. We demonstrated that mice transgenically expressing mouse PrP with deletion of the OR region on the PrP knockout background, designated Tg(PrPΔOR)/ Prnp0 / 0 mice, did not show reduced susceptibility to RML scrapie prions, with abundant accumulation of PrPSc ΔOR in their brains. We show here that Tg(PrPΔOR)/ Prnp0 / 0 mice were highly resistant to BSE prions, developing the disease with markedly elongated incubation times after infection with BSE prions. The conversion of PrPΔOR into PrPSc ΔOR was markedly delayed in their brains. These results suggest that the OR region may have a crucial role in the conversion of PrPC into PrPSc after infection with BSE prions. However, Tg(PrPΔOR)/ Prnp0 / 0 mice remained susceptible to RML and 22L scrapie prions, developing the disease without elongated incubation times after infection with RML and 22L prions. PrPSc ΔOR accumulated only slightly less in the brains of RML- or 22L-infected Tg(PrPΔOR)/ Prnp0 / 0 mice than PrPSc in control wild-type mice. Taken together, these results indicate that the OR region of PrPC could play a differential role in the pathogenesis of BSE prions and RML or 22L scrapie prions. IMPORTANCE Structure-function relationship studies of PrPC conformational conversion into PrPSc are worthwhile to understand the mechanism of the conversion of PrPC into PrPSc We show here that, by inoculating Tg(PrPΔOR)/ Prnp0 / 0 mice with the three different strains of RML, 22L, and BSE prions, the OR region could play a differential role in the conversion of PrPC into PrPSc after infection with RML or 22L scrapie prions and BSE prions. PrPΔOR was efficiently converted into PrPSc ΔOR after infection with RML and 22L prions. However, the conversion of PrPΔOR into PrPSc ΔOR was markedly delayed after infection with BSE prions. Further investigation into the role of the OR region in the conversion of PrPC into PrPSc after infection with BSE prions might be helpful for understanding the pathogenesis of BSE prions., (Copyright © 2017 American Society for Microbiology.)- Published
- 2017
- Full Text
- View/download PDF
8. Mouse prion protein (PrP) segment 100 to 104 regulates conversion of PrP(C) to PrP(Sc) in prion-infected neuroblastoma cells.
- Author
-
Hara H, Okemoto-Nakamura Y, Shinkai-Ouchi F, Hanada K, Yamakawa Y, and Hagiwara K
- Subjects
- Amino Acid Motifs, Amino Acid Sequence, Animals, Cell Line, Chickens, Humans, Mice, Molecular Sequence Data, PrPC Proteins chemistry, PrPC Proteins genetics, PrPC Proteins metabolism, PrPSc Proteins chemistry, PrPSc Proteins genetics, PrPSc Proteins metabolism, Prion Proteins, Prions genetics, Sequence Alignment, Neuroblastoma metabolism, Prion Diseases metabolism, Prions chemistry, Prions metabolism
- Abstract
Prion diseases are characterized by the replicative propagation of disease-associated forms of prion protein (PrP(Sc); PrP refers to prion protein). The propagation is believed to proceed via two steps; the initial binding of the normal form of PrP (PrP(C)) to PrP(Sc) and the subsequent conversion of PrP(C) to PrP(Sc). We have explored the two-step model in prion-infected mouse neuroblastoma (ScN2a) cells by focusing on the mouse PrP (MoPrP) segment 92-GGTHNQWNKPSKPKTN-107, which is within a region previously suggested to be part of the binding interface or shown to differ in its accessibility to anti-PrP antibodies between PrP(C) and PrP(Sc). Exchanging the MoPrP segment with the corresponding chicken PrP segment (106-GGSYHNQKPWKPPKTN-121) revealed the necessity of MoPrP residues 99 to 104 for the chimeras to achieve the PrP(Sc) state, while segment 95 to 98 was replaceable with the chicken sequence. An alanine substitution at position 100, 102, 103, or 104 of MoPrP gave rise to nonconvertible mutants that associated with MoPrP(Sc) and interfered with the conversion of endogenous MoPrP(C). The interference was not evoked by a chimera (designated MCM2) in which MoPrP segment 95 to 104 was changed to the chicken sequence, though MCM2 associated with MoPrP(Sc). Incubation of the cells with a synthetic peptide composed of MoPrP residues 93 to 107 or alanine-substituted cognates did not inhibit the conversion, whereas an anti-P8 antibody recognizing the above sequence in PrP(C) reduced the accumulation of PrP(Sc) after 10 days of incubation of the cells. These results suggest the segment 100 to 104 of MoPrP(C) plays a key role in conversion after binding to MoPrP(Sc).
- Published
- 2012
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.