Jian-Ming Chen

Chinese Center For Disease Control And Prevention, Peping, Beijing, China

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Publications (20)26.76 Total impact

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    ABSTRACT: A definitive diagnosis of Creutzfeldt-Jakob disease (CJD) can only be made by neuropathologic examination and demonstration of typical pathologic changes and the pathologic prion protein in central nervous tissues. This study investigated the diagnostic sensitivity and specificity of the microtubule-association protein tau in cerebrospinal fluid (CSF) from Chinese patients with sporadic CJD. Two hundred two CSF samples from clinically suspected patients with sporadic CJD were analyzed for tau protein by enzyme-linked immunosorbent assay and for the signal transduction regulatory protein 14-3-3 protein by immunoblot. Remarkably increased levels of tau protein and increased incidence of 14-3-3 positivity were observed in probable CJD, when compared with possible CJD and others. With a threshold of 1400 pg/mL, tau determination showed a sensitivity of 90% and a specificity of 94% for the diagnosis of probable CJD. The combination of raised tau and positive 14-3-3 increased the specificity but slightly reduced the sensitivity. Statistical analysis indicated that the raised level of tau positively correlated with the presence of 14-3-3 in CSF but not with other main clinical features, eg, age, gender, clinical manifestations and sampling time. These data suggest that Chinese patients with probable CJD have similar increased levels of tau in the CSF as in Caucasian patients. Measurement of CSF tau will be another potential technique for antemortem CJD diagnosis.
    The American Journal of the Medical Sciences 10/2010; 340(4):291-5. DOI:10.1097/MAJ.0b013e3181e92a1f · 1.52 Impact Factor
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    ABSTRACT: We compared clinical data from two related Chinese patients with fatal familial insomnia (FFI) and collected information about their pedigree. The clinical features in the two cases were similar and included initial progressive insomnia and sympathetic activation, which persisted throughout the clinical course. A total of 135 members of this family, across seven generations, were retrospectively investigated. Eleven family members, including the two FFI cases, were found to have died with similar neurological problems. Analysis of PRNP in 32 family members revealed eleven carrying the D178N allele, including the two FFI patients. Spongiform degeneration in brains was not found, but gliosis was obvious in the thalamus of the two cases at postmortem. Proteinase K-resistant prion protein (PrP) was not found in proband's brain by immunohistochemistry, but observed in some areas of brain for both cases by PrP-specific Western blot. Investigation of the pedigree has led to the identification of an additional 9 family members who had similar clinical symptoms and 9 currently healthy individuals with the D178N mutation.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 03/2010; 10(2):292-7. DOI:10.1016/j.meegid.2010.01.007 · 3.26 Impact Factor
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    ABSTRACT: Different neurodegenerative disorders like prion disease, is caused by protein misfolding conformers. Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic. To investigate the possible mechanism of neurotoxicity due to accumulation of PrP in cytosol, a PrP mutant lacking the signal and GPI (CytoPrP) was introduced into the SH-SY5Y cell. MTT and trypan blue assays indicated that the viability of cells expressing CytoPrP was remarkably reduced after treatment of MG-132. Obvious apoptosis phenomena were detected in the cells accumulated with CytoPrP, including loss of mitochondrial transmembrane potential, increase of caspase-3 activity, more annexin V/PI-double positive-stained cells and reduced Bcl-2 level. Moreover, DNA fragmentation and TUNEL assays also revealed clear evidences of late apoptosis in the cells accumulated CytoPrP. These data suggest that the accumulation of CytoPrP in cytoplasm may trigger cell apoptosis, in which mitochondrial relative apoptosis pathway seems to play critical role.
    BMB reports 08/2009; 42(7):444-9. DOI:10.5483/BMBRep.2009.42.7.444 · 1.99 Impact Factor
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    ABSTRACT: Inherited Prion diseases are characterized by mutations in the PRNP gene predispose to disease by causing the expression of abnormal PrP protein. We report a 58-year-old Chinese female with mutation in codon 188 (T188K) of the PRNP gene, while the codon 129 was a methionine homozygous genotype. The patient displayed 4-year long slowly progressive sleeping disturbance and rapid exacerbation of neurological status after other neurological manifestations appeared. Cerebral spinal fluid 14-3-3 protein was positive.
    Cases Journal 05/2009; 2:7820. DOI:10.1186/1757-1626-2-7820
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    ABSTRACT: To establish a stable PrP(Sc) panel from brain tissues of experimental hamsters infected with scrapie agent 263K for evaluating diagnostic techniques of human and animals' prion diseases. Thirty brain tissue samples from hamsters intracerebrally infected with scrapie strain 263K and another 30 samples from normal hamsters were selected to prepare 10%, 1%, and 0.5% brain homogenates, which were aliquoted into stocks. PrP(Sc) in each brain homogenate was determined by proteinase K digestions followed by Western blot assay and partially by immunohistochemistry. Stability and glycoforms of PrP(Sc) were repeatedly detected by PrP(Sc)-specific Western blots in half a year and 3 years later. PrP(Sc) signals were observed in all 10% brain homogenates of infected hamsters. Twenty out of 30 stocks and 19 out of 30 stocks were PrP(Sc) positive in 1% and 0.5% brain homogenatesof infected hamsters, respectively. Twenty-seven out of 30 stocks presented three positive bands in 10% brain homogenates, whereas none of 1% and 0.5% homogenates contained 3 bands. The detection of PrP(Sc)-specific signals stored in half a year and 3 years later demonstrated that the ratio of PrP(Sc) positive samples and glycoforms was almost unchanged. All normal hamsters' brain homogenates were PrP(Sc) negative. A PrP(Sc) panel of prion disease can be established, which displays reliably stable PrP(Sc)-specific signals and glycoforms.
    Biomedical and Environmental Sciences 05/2009; 22(2):151-6. DOI:10.1016/S0895-3988(09)60038-6 · 1.26 Impact Factor
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    ABSTRACT: To study the circulation, distribution, and genomic diversity of HPVs in common warts in Beijing area of China. Forty eight patients with pathologically diagnosed common warts were screened for the presence of HPV with HPV type-specific PCR and direct sequencing analysis. The genomic diversity of HPVs prevalent in Chinese patients was analyzed based on LCR. Forty one (85.5%) samples were positive for HPV DNA, 13 (31.7%)--HPV-57, 12 (29.3%)--HPV-1a, 7 (17%)--HPV-27 and 5(12.2%)--HPV-2a. Four cases were infected with two different HPV types, two (4.9%) with HPV-1a and HPV-27, one (2.4%) with HPV-1 and HPV-57 and one (2.4%) with HPV-27 and HPV-57. In contrast to the prevalence of single strain of novel HPV-57 variant and HPV-1 prototype, two HPV-2 and three HPV-27 novel variants were found to circulate in Beijing. HPV-1, -2, -27 and -57 are predominantly prevalent in patients with common warts in Beijing.
    Biomedical and Environmental Sciences 03/2009; 22(1):55-61. DOI:10.1016/S0895-3988(09)60023-4 · 1.26 Impact Factor
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    ABSTRACT: To investigate the epidemiological, genealogic characteristic, familial history of the families with fatal familial insomnia, its clinical and pathological features as well as the heredity rule of related genes. 135 familial members of 7 eras were studied. Vein blood samples from patients as well as from some familial members were collected. PRNP gene was studied with PCR, its serial was determined and then authenticated with Nsp I . Brain tissue was obtained for neuropathological test and PrP(Sc) test with Western blot method. Clinical symptoms of the 2 diagnosed cases were typical. 11 familial members died of similar neural disease. 32 samples of their familial members, codon at D178N of PRNP of 11 members was mutated, with mutation rate as 34.38% while D129N showed as methionine. Brain tissue of both probands denaturalized into spongiform and the nerve fiber was absent but PrP(Sc) protein was identified. Genealogy was described in the family with fatal familial insomnia since the patients had typical clinical symptoms and pathological characteristics. It seemed necessary to confirm cases of fatal familial insomnia and their genealogy with epidemiological data and to investigate its gene characteristics as well as with neuropathological and Western blot tests.
    Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 02/2009; 30(1):1-5.
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    ABSTRACT: Transmissible spongiform encephalopathies (TSEs), or prion diseases, are transmissible neurodegenerative disorders of protein conformation. This group of diseases is caused by infectious agents, termed prions, which can convert normal conformation (PrP(C)) into misfolded protein (PrP(Sc)). The infectivity of non-neuronal tissues has been wildly addressed, but the propagating features and the biochemical properties of prion generated from these tissues are only partially settled. In this study, utilizing protein misfolding cyclic amplification (PMCA), the in vitro conversion of PrP(C) into PrP(Sc) in spleen and muscle tissues can be induced by PrP(Sc) produced in vivo. The further propagation of newly formed PrP(Sc) in normal brain and some of the biochemical properties of new PrP(Sc) are similar as the brain-derived prions, implying the naturally infectious pathway of prion from peripheral generation to neuro-invasion. However, compared with the brain-derived PrP(Sc), the weaker resistance of new PrP(Sc) to some inactivated agents, i.e. sodium hydroxide and thermal inactivation, are observed. Our data provide the reliable evidence that the brain-derived PrP(Sc) can utilize the PrP(C) from non-neuronal tissues for its propagation. Similarity of the replicative ability in PMCA in vitro and the infectivity in vivo highlights the possibility to use PMCA instead of bioassay to investigate the propagation of prion.
    Virus Research 02/2009; 141(1):26-33. DOI:10.1016/j.virusres.2008.12.010 · 2.83 Impact Factor
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    ABSTRACT: Human transmissible spongiform encephalopathies (HTSE), or Creutzfeldt-Jakob disease (CJD), is a group of rare and fatal diseases in central nervous system. Since outbreak of bovine spongiform encephalopathy (BSE) and variant CJD, a worldwide CJD surveillance network has been established under the proposition of WHO. In China, a national CJD surveillance system has started since 2002. The data of CJD surveillance from 2006 to 2007 was analyzed. Total 12 provinces are included in CJD surveillance system. The surveillance unit in each province consists of one or two sentinel hospitals and the provincial CDC. All suspected CJD cases reported from CJD surveillance were diagnosed and subtyped based on the diagnostic criteria for CJD issued by WHO. Total 192 suspected CJD cases were reported and 5 genetic CJD, 51 probable and 30 possible sporadic CJD (sCJD) cases were diagnosed. The collected sCJD cases distribute sporadically without geographical clustering and seasonal relativity and the highest incidences in both probable and possible sCJD cases appeared in the group of 60-69 year. The most common three foremost symptoms were progressive dementia, cerebellum and mental-related symptoms. The probable sCJD patients owning both typical EEG alteration and CSF protein 14-3-3 positive have more characteristic clinical syndromes than the ones having only one positive. The polymorphisms of codon 129 of all tested reported cases shows typical patterns of Han Chinese as previous reports, that M129M are predominant whereas M129V are seldom. Chinese CJD patients possessed similar epidemiological and clinical characteristics as worldwide.
    BMC Public Health 11/2008; 8:360. DOI:10.1186/1471-2458-8-360 · 2.32 Impact Factor
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    ABSTRACT: To explore the possible molecular interaction between CK2 and PrP, the full length sequences of human CK2alpha and CK2beta genes were amplified with RT-PCR using the mRNA from cell line SH-SY5Y as the template, and then the fusion proteins HIS-CK2alpha and GST-HIS-CK2beta were expressed in E. coli. The interaction between CK2 and PrP was evaluated with immunoprecipitation and pull-down assays. The results demonstrated that recombinant PrP bound specifically with CK2alpha, but not with CK2beta. The native CK2 and PrP in the hamster brains interacted each other, forming protein complexes. The domain responsible for interacting with CK2alpha was located at the C-terminal segment of PrP (residues 90-231). This study proposed reliable experimental data for the molecular interaction between PrP and CK2alpha, both in recombinant and native categories. These results supply scientific clues for further assessing the potential biological significance of the interaction of PrP with CK2 and possible role of CK2 in the pathogenesis of prion diseases.
    Bing du xue bao = Chinese journal of virology / [bian ji, Bing du xue bao bian ji wei yuan hui] 10/2008; 24(5):335-9.
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    ABSTRACT: Common warts are close associated with HPVs infection. In this study, we amplified and sequenced the LCR fragment and E2 gene of HPV-2 that infected the patient of extensive common wart with cutaneous horns, and we constructed the recombinant CAT-reporter plasmids pBLCAT-LCR containing HPV-2 prototype or variant LCR and mammalian expression plasmids pcDNA3. 1-E2 containing prototype or variant E2 ORF individually. The promoter activities of HPV-2 variant and the transcriptional repression activities of the mutated E2 protein were evaluated by transient transfection into HeLa cells. The results showed that there were several mutations in LCR and E2 gene of HPV-2 variant. Compared with the prototype, the viral early promoter activity of variant was significantly increased uder the control of LCR. Compared with the wild type E2 protein, the transcriptional repression activities of the mutated E2 protein was abolished partially. We speculate herein that increased promoter activities and decreased repression effect of the mutated E2 protein are linked, at least partially, with the clinical phenotypes of the uncommon huge common wart.
    Bing du xue bao = Chinese journal of virology / [bian ji, Bing du xue bao bian ji wei yuan hui] 08/2008; 24(4):268-71.
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    ABSTRACT: To establish a new Western blotting assay for PrP(Sc) detection, we optimized the Western blotting assay with a precipitation procedure of streptomycin sulfate. After digestion with PK, 10% scrapie infected hamster brain homogenates were incubated with 60 mmol/L streptomycin and the precipitated PrP(Sc) was recovered by centrifugation. The enrichment of PrP(Sc) by streptomycin sulfate precipitation was evaluated using Western blotting assay. The results showed streptomycin could bind to PK-treated PrP(Sc), forming high molecular masses, but not influence the glycosylated patterns on SDS-PAGE. Western blot assay revealed that the detective sensitivity of the streptomycin-precipitation PrP(Sc) was remarkably improved. As a sensitive, specific, rapid and flexible protocol for PrP(Sc), the protocol in this study has the potential utility, alone or combined with other techniques, for the detection of low level PrP(Sc) in the specimens from central nerve system, or from peripheral organs or body fluids.
    Bing du xue bao = Chinese journal of virology / [bian ji, Bing du xue bao bian ji wei yuan hui] 06/2008; 24(3):185-9.
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    ABSTRACT: Microtubule dynamics is essential for many vital cellular processes such as in intracellular transport, metabolism, and cell division. Some evidences demonstrate that PrP may associate with microtubular cytoskeleton and its major component, tubulin. In the present study, the molecular interaction between PrP and tubulin was confirmed using pull-down assays, immunoprecipitation and ELISA. The interacting regions within PrP with tubulin were mapped in the N-terminus of PrP spanning residues 23-50 and 51-91. PrP octapeptide repeats are critical for the binding activity with tubulin, that the binding activity of PrP with tubulin became stronger along with the number of the octapeptide repeats increased. Microtubule assembly assays, sedimental tests and transmission electron microscopy demonstrated that the full-length PrP (aa 23-231) obviously inhibited the microtubule polymerization processes in vitro, whereas the N- (aa 23-91) and C- (aa 91-231) terminal peptides of PrP did not affect microtubule polymerization. Moreover, the familial Cruetzfeldt Jacob disease (fCJD) related PrP mutants with inserted or deleted octapeptide repeats showed much stronger inhibitive capacities on the microtubule dynamics in vitro than wild-type PrP. Our data highlight a potential role of PrP in regulating the microtubule dynamics in neurons.
    Archives of Biochemistry and Biophysics 03/2008; 470(1):83-92. DOI:10.1016/j.abb.2007.11.007 · 3.04 Impact Factor
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    ABSTRACT: To establish a sandwich ELISA method for detecting vascular endothelial growth factor (VEGF) in sera of population and the patients with hepatocellular carcinoma (HCC). Full length and two truncated human VEGF cDNA sequences were amplified from a commercial plasmid pBLAST49-hVEGF by PCR and inserted into the prokaryotic-expression plasmid pET-32a or pGEX-2T. Various VEGF proteins were expressed and purified from E. coli in His-Trx or GST fusion forms. The specific VEGF antibodies were elicited in experimental rabbits and mice by immunization of the full length VEGF fusion protein His-Trx-VEGF1-165. After purification of antibodies with chromatograph of Protein G, a sandwich ELISA technique was established. Serum VEGF levels were evaluated in 229 adults and 291 HCC patients. SDS-PAGE displayed that the molecular weights of the expressed full length (His-Trx-VEGF1-165), N-terminal (His-Trx-VEGF1-100) and C-terminal (GST-VEGF100-165) human VEGF fusion proteins were about 38KD, 31KD, and 33KD, respectively. Western blots confirmed that the prepared antisera were able to recognize both prokaryoticly and eukaryoticly expressed recombinant VEGF proteins. Assays of serially diluted His-Trx-VEGF1-100 by the established sandwich ELISA method showed that the linear range of the standard curve was 0.625-320 ng/mL, with the squared correlation coefficient R2 = 0.991. Screening of a serum panel containing 291 serum samples of HCC patients and 229 health adults revealed that the average VEGF level in HCC patients was higher than that in healthy controls, with a statically significant difference. The established sandwich ELISA reflects the level of serum VEGF and provide scientific basis for screening metastasis and recurrence of HCC using serum VEGF as an index.
    Biomedical and Environmental Sciences 03/2008; 21(1):69-74. DOI:10.1016/S0895-3988(08)60009-4 · 1.26 Impact Factor
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    ABSTRACT: The methods for detecting and typing human papillomavirus (HPV) in most molecular epidemiological surveys of verrucae vulgaris were based on PCR followed by sequencing or hybridization. However, the amplification efficacies of different assays for the detection of HPV DNAs varied largely. In this study, a novel multiplex PCR method to detect and type the HPVs (HPV-1, -2, -27 and -57) related to verrucae vulgaris was described. This method allows detecting and typing HPV DNA simultaneously in one reaction based on the length of the PCR products after electrophoresis. The sensitivity and specificity of this multiplex PCR method was assessed with the standard template panels and the spiking sample panels, and evaluated with the clinical samples, compared with PCR assay with primer MY09/11. The results showed the novel method had reliable clinical sensitivity (97.6%) and specificity (100%), significantly higher than that of the PCR using consensus primer, MY09/11. In addition, this method can effectively detect multiple HPV infection within the lesions. This simplified, economic and time-saving multiplex PCR method provides a useful additional tool for the clinical epidemiological study of verrucae vulgaris.
    Journal of Virological Methods 02/2008; 147(1):72-7. DOI:10.1016/j.jviromet.2007.08.005 · 1.88 Impact Factor
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    ABSTRACT: To address the possible alteration of casein kinase 2 (CK2) in transmissible spongiform encephalopathies (TSEs), the levels and patterns of CK2 in the brain tissues of hamsters or C57BL mice inoculated intracerebrally with scrapie agents 263K or 139A were evaluated by Western blots, followed by quantitative analysis. Specific semi-quantitative RT-PCR for evaluating the mRNA transcripts of CK2 subunits was performed in parallel. Compared with normal animals, the levels of CK2alpha and CK2beta in the brains of infected hamsters and mice were significantly decreased, regardless of which scrapie agent was. However, the expression of CK2alpha' or CK2alpha'/CK2alpha'' in the animals infected with agents 263K or 139A was considerably increased. Furthermore, decreases of CK2alpha and CK2beta and increases of CK2alpha'/CK2alpha'' were observed in cerebella homogenates from one familial Creutzfeldt-Jakob disease (fCJD) case and one fatal familial insomnia (FFI) case. These results suggest that alterations of CK2 subunits in brains are illness-correlative phenomena in TSEs and indicate a potential linkage of CK2 changes with the pathogenesis of prion diseases.
    Archives of Virology 02/2008; 153(6):1013-20. DOI:10.1007/s00705-008-0084-z · 2.28 Impact Factor
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    ABSTRACT: To describe the incidence condition and characteristic of Creutzfeldt-Jakob disease (CJD) in China. The clinical and epidemical information of patients from China CJD surveillance network was analyzed. Blood and cerebrospinal fluid (CSF) specimens from these patients were differently collected to be used to detect the 14-3-3 protein in the CSF and to analyze the PRNP gene. Ten possible and 8 probable clinically diagnosed CJD patients were found. These patients had sporadic CJD. There were no geographic clustering and occupational risk with these patients. The mean age at onset of disease was approximately 60 years. The male to female ratio was approximately 1:1; rapidly progressive dementia was the main early symptom, which was present in 44% of patients. The geographic distribution, occupation, the ratio of male to female and the mean age of onset were consistent with the characteristics of sporadic CJD.
    Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of experimental and clinical virology 10/2007; 21(3):205-7.
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    ABSTRACT: To assess the influences of the mutations within the long control region (LCR) and E2 open reading frame (ORF) of the human papillomavirus-2 (HPV-2) isolates from patients with extensive verrucae vulgaris with cutaneous horns in the activities of the viral early promoters. A PCR method was applied for screening HPV DNA in the lesion specimens and the complete HPV-2 genomes was analyzed. Recombinant CAT-reporter plasmids containing various HPV-2 LCRs and mammalian expression plasmids containing E2 ORF were constructed. The promoter activity was evaluated by transient transfection. The whole HPV-2 genomes were obtained from both patients. Several mutations in LCR and mutations leading to alterations of amino acids in E2 protein were identified in isolate-1, while a few point mutations in LCR were seen in isolate-2. Under the control of LCRs, the viral early promoter activities of isolate-1 and isolate-2 were increased 3- and 2-fold, respectively. Alterations of amino acids in E2 protein of isolate-1 partially abolished its promoter repressive activity. Compared with that of prototype HPV-2, the promoter activity of isolate-1 in the presence of its E2-expressing plasmid was significantly increased. The increased promoter activities might be linked, at least partially, to the clinical phenotypes of the uncommon huge verrucae vulgaris.
    Intervirology 02/2007; 50(5):353-60. DOI:10.1159/000107706 · 1.77 Impact Factor
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    ABSTRACT: In order to further study the potential interaction between PrP protein and the tubulin and identify the binding region in PrP with tubulin, native tubulin was extracted from rabbit brian tissues, while various recombinant PrP proteins were expressed and purified. The possible molecular interaction between various PrP fusion proteins and tubulin was tested by pull-down and immunoprecipitation assays. Remarkable molecular interaction between the full length PrP and tubulin was observed by pull-down and immunoprecipitation assays. Subsequently, the binding regions within PrP with tubulin were firstly mapped in the aa 23 -- 91 region within N-terminus of PrP peptide. The studies of the association of PrP with tubulin may further provide insight into the unresolved mechanism of active transport of PrP protein in neurons and possible cellular pathways by which prion causes disease.
    Bing du xue bao = Chinese journal of virology / [bian ji, Bing du xue bao bian ji wei yuan hui] 02/2007; 23(1):28-32.
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    ABSTRACT: The most essential and crucial step during the pathogenesis of transmissible spongiform encephalopathy is the conformational change of cellular prion protein (PrP(C)) to pathologic isoform (PrP(Sc)). A lot of data revealed that caveolae-like domains (CLDs) in the cell surface were the probable place where the conversion of PrP proteins happened. Apolipoprotein E (ApoE) is an apolipoprotein which is considered to play an important role in the development of Alzheimer's disease and other neurodegenerative diseases by forming protein complex through binding to the receptor located in the clathrin-coated pits of the cell surface. In this study, a 914-bp cDNA sequence encoding human ApoE3 was amplified from neuroblastoma cell line SH-SY5Y. Three human ApoE isomers were expressed and purified from Escherichia coli. ApoE-specific antiserum was prepared by immunizing rabbits with the purified ApoE3. GST/His pull-down assay, immunoprecipitation and ELISA revealed that three full-length ApoE isomers interact with the recombinant full-length PrP protein in vitro. The regions corresponding to protein binding were mapped in the N-terminal segment of ApoE (amino acid 1-194) and the N-terminal of PrP (amino acid 23-90). Moreover, the recombinant PrP showed the ability to form a complex with the native ApoE from liver tissues. Our data provided direct evidence of molecular interaction between ApoE and PrP. It also supplied scientific clues for assessing the significance of CLDs on the surface of cellular membrane in the process of conformational conversion from PrP(C) to PrP(Sc) and probing into the pathogenesis of transmissible spongiform encephalopathy.
    Acta Biochimica et Biophysica Sinica 10/2006; 38(9):593-601. DOI:10.1111/j.1745-7270.2006.00209.x · 2.09 Impact Factor

Publication Stats

149 Citations
26.76 Total Impact Points

Institutions

  • 2009–2010
    • Chinese Center For Disease Control And Prevention
      Peping, Beijing, China
    • Jiangsu Provincial Center for Disease Control and Prevention
      Chiang-tu, Jiangsu Sheng, China
  • 2007–2010
    • Beijing Centers for Disease Control and Prevention
      Peping, Beijing, China
  • 2007–2008
    • Shanghai Jiao Tong University
      • School of Medicine
      Shanghai, Shanghai Shi, China