• 제목/요약/키워드: prion protein

검색결과 43건 처리시간 0.034초

Removal of the Glycosylation of Prion Protein Provokes Apoptosis in SF126

  • Chen, Lan;Yang, Yang;Han, Jun;Zhang, Bao-Yun;Zhao, Lin;Nie, Kai;Wang, Xiao-Fan;Li, Feng;Gao, Chen;Dong, Xiao-Ping;Xu, Cai-Min
    • BMB Reports
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    • 제40권5호
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    • pp.662-669
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    • 2007
  • Although the function of cellular prion protein (PrP$^C$) and the pathogenesis of prion diseases have been widely described, the mechanisms are not fully clarified. In this study, increases of the portion of non-glycosylated prion protein deposited in the hamster brains infected with scrapie strain 263K were described. To elucidate the pathological role of glycosylation profile of PrP, wild type human PrP (HuPrP) and two genetic engineering generated non-glycosylated PrP mutants (N181Q/N197Q and T183A/T199A) were transiently expressed in human astrocytoma cell line SF126. The results revealed that expressions of non-glycosylated PrP induced significantly more apoptosis cells than that of wild type PrP. It illustrated that Bcl-2 proteins might be involved in the apoptosis pathway of non-glycosylated PrPs. Our data highlights that removal of glycosylation of prion protein provokes cells apoptosis.

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.

Heterogeneous interaction network of yeast prions and remodeling factors detected in live cells

  • Pack, Chan-Gi;Inoue, Yuji;Higurashi, Takashi;Kawai-Noma, Shigeko;Hayashi, Daigo;Craig, Elizabeth;Taguchi, Hideki
    • BMB Reports
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    • 제50권9호
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    • pp.478-483
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    • 2017
  • Budding yeast has dozens of prions, which are mutually dependent on each other for the de novo prion formation. In addition to the interactions among prions, transmissions of prions are strictly dependent on two chaperone systems: the Hsp104 and the Hsp70/Hsp40 (J-protein) systems, both of which cooperatively remodel the prion aggregates to ensure the multiplication of prion entities. Since it has been postulated that prions and the remodeling factors constitute complex networks in cells, a quantitative approach to describe the interactions in live cells would be required. Here, the researchers applied dual-color fluorescence cross-correlation spectroscopy to investigate the molecular network of interaction in single live cells. The findings demonstrate that yeast prions and remodeling factors constitute a network through heterogeneous protein-protein interactions.

Stem Cell Biology, 최근의 진보 (Recent Advancement in the Stem Cell Biology)

  • 한창열
    • Journal of Plant Biotechnology
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    • 제33권3호
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    • pp.195-207
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    • 2006
  • Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.

Cellular Prion Protein Enhances Drug Resistance of Colorectal Cancer Cells via Regulation of a Survival Signal Pathway

  • Lee, Jun Hee;Yun, Chul Won;Lee, Sang Hun
    • Biomolecules & Therapeutics
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    • 제26권3호
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    • pp.313-321
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    • 2018
  • Anti-cancer drug resistance is a major problem in colorectal cancer (CRC) research. Although several studies have revealed the mechanism of cancer drug resistance, molecular targets for chemotherapeutic combinations remain elusive. To address this issue, we focused on the expression of cellular prion protein ($PrP^C$) in 5-FU-resistant CRC cells. In 5-FU-resistant CRC cells, $PrP^C$ expression is significantly increased, compared with that in normal CRC cells. In the presence of 5-FU, $PrP^C$ increased CRC cell survival and proliferation by maintaining the activation of the PI3K-Akt signaling pathway and the expression of cell cycle-associated proteins, including cyclin E, CDK2, cyclin D1, and CDK4. In addition, $PrP^C$ inhibited the activation of the stress-associated proteins p38, JNK, and p53. Moreover, after treatment of 5-FU-resistant CRC cells with 5-FU, silencing of $PrP^C$ triggered apoptosis via the activation of caspase-3. These results indicate that $PrP^C$ plays a key role in CRC drug resistance. The novel strategy of combining chemotherapy with $PrP^C$ targeting may yield efficacious treatments of colorectal cancer.

Single-nucleotide polymorphisms in prion protein gene of the Korean subspecies of Chinese water deer

  • Jeong, Hyun-Jeong;Lee, Joong-Bok;Park, Seung-Yong;Song, Chang-Seon;Kim, Bo-Sook;Rho, Jung-Rae;Yoo, Mi-Hyun;Jeong, Byung-Hoon;Kim, Yong-Sun;Choi, In-Soo
    • 대한수의학회지
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    • 제49권1호
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    • pp.59-62
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    • 2009
  • Susceptibility to chronic wasting disease (CWD) in cervid species has been associated with polymorphisms in the prion protein gene (PRNP). The single nucleotide polymorphisms (SNPs) were found in the PRNP of the Korean subspecies of Chinese water deer via analyses of the DNA sequences obtained from 34 individual deer. Two SNPs were detected at codons 77 and 100. One SNP at codon 77 encoding Glycine was determined to be a silent mutation but the other SNP detected at codon 100 induced an amino acid change, from Asparagine to Serine. The prion protein (PrP) amino acid sequence of the water deer showed 98.8-99.2% homology with those of American elk, white-tailed deer and mule deer. The PrP of the water deer contained amino acid residues closely related with CWD-susceptibility. This study is the first to describe genetic variations in the PRNP of the Korean subspecies of Chinese water deer.

Disulfide Bond as a Structural Determinant of Prion Protein Membrane Insertion

  • Shin, Jae Yoon;Shin, Jae Il;Kim, Jun Seob;Yang, Yoo Soo;Shin, Yeon-Kyun;Kim, Kyeong Kyu;Lee, Sangho;Kweon, Dae-Hyuk
    • Molecules and Cells
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    • 제27권6호
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    • pp.673-680
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    • 2009
  • Conversion of the normal soluble form of prion protein, PrP ($PrP^C$), to proteinase K-resistant form ($PrP^{Sc}$) is a common molecular etiology of prion diseases. Proteinase K-resistance is attributed to a drastic conformational change from ${\alpha}$-helix to ${\beta}$-sheet and subsequent fibril formation. Compelling evidence suggests that membranes play a role in the conformational conversion of PrP. However, biophysical mechanisms underlying the conformational changes of PrP and membrane binding are still elusive. Recently, we demonstrated that the putative transmembrane domain (TMD; residues 111-135) of Syrian hamster PrP penetrates into the membrane upon the reduction of the conserved disulfide bond of PrP. To understand the mechanism underlying the membrane insertion of the TMD, here we explored changes in conformation and membrane binding abilities of PrP using wild type and cysteine-free mutant. We show that the reduction of the disulfide bond of PrP removes motional restriction of the TMD, which might, in turn, expose the TMD into solvent. The released TMD then penetrates into the membrane. We suggest that the disulfide bond regulates the membrane binding mode of PrP by controlling the motional freedom of the TMD.

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.

Gerstmann-Sträussler-Scheinker병: 증례 보고 (Gerstmann-Sträussler-Scheinker Disease: A Case Report)

  • 신민지;김동현;허영진;백진욱;윤수영;정해웅
    • 대한영상의학회지
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    • 제84권3호
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    • pp.745-749
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    • 2023
  • Gerstmann-Strssler-Scheinker (이하 GSS) disease는 드문 유전성 프라이온 질환으로 초기에 발생해 진행하는 소뇌실조와 후기에 발생하는 인지기능 저하가 특징적이다. 저자들은 진행하는 보행장애와 5개월 후 발생한 구음 장애, 인지 기능 저하를 주소로 내원한 39세 남성 환자의 증례를 보고하고자 한다. 뇌 MRI에서 양측 대뇌피질과 기저핵, 시상에 확산 저하를 동반한 T2 강조영상에서의 고신호 강도 병변이 관찰되었다. 환자는 모두 40-50대에 비슷한 증상을 호소하였던 가족력을 동반하였으며 PRNP 유전자 검사를 통해 GSS로 확진되었다.