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apolipoprotein e mimetic peptide protects against diffuse brain injury

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Neural Regeneration Research 2014年第5期9卷 463-473页

作者： Yaning Zhao Jianmin Li Qiqun Tang Junling Gao Changxiang Chen Liwei Jing Pan Zhang Shuxing Li College of Rehabilitation Hebei United University Affiliated Hospital of Hebei United University

apolipoprotein e plays a crucial role in inhibiting chronic neurodegenerative processes. Howev-er, its impact on neurological function following diffuse brain injury is still unclear. This study was designed to evaluate the therapeutic effects and mechanisms of action of apolipoprotein e mimetic peptide on diffuse brain injury. apolipoprotein e mimetic peptide was administered into the caudal vein of rats with diffuse brain injury before and after injury. We found that apo-lipoprotein e mimetic peptide signiifcantly decreased the number of apoptotic neurons, reduced extracellular signal-regulated kinase1/2 phosphorylation, down-regulated Bax and cytochrome c expression, decreased malondialdehyde content, and increased superoxide dismutase activity in a dose-dependent manner. These experimental ifndings demonstrate that apolipoprotein e mimetic peptide improves learning and memory function and protects against diffuse brain injury-induced apoptosis by inhibiting the extracellular signal-regulated kinase1/2-Bax mito-chondrial apoptotic pathway.

关键词： nerve regeneration brain injury apolipoprotein e diffuse brain injury learning and memory extracellular signal-regulated kinase Bax mitochondria reactive oxygen species apoptosis Scientific Research and,Development Plan of Hebei Province in China neural regeneration

apolipoprotein e polymorphisms increase the risk of post-stroke depression

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Neural Regeneration Research 2016年第11期11卷 1790-1796页

作者： Xue-bin Li Jie Wang An-ding Xu Jian-min Huang Lan-qing Meng Rui-ya Huang Jun-li Wang Stroke Center & Neurology Division the First Affiliated Hospital of Jinan University Department of Nephrology the Affiliated Hospital of Youjiang Medical University for Nationalities Department of Neurology the Affiliated Hospital of Youjiang Medical University for Nationalities Department of Laboratory Medicines the Affiliated Hospital of Youjiang Medical University for Nationalities

Recent reports have shown that apolipoprotein e （APOe） polymorphisms are involved in neurodegenerative disease. However, it is unclear whether APOe affects post-stroke depression. Accordingly, we hypothesized that APOe polymorphisms modify the risk of post-stroke depression. Here, we performed a hospital-based case-control study （including 76 cerebral infarction cases with post-stroke depression, 88 cerebral infarction cases without post-stroke depression, and 109 controls without any evidence of post-stroke depression or cerebral infarction） to determine possible association between APOe rs429358 and rs7412 polymorphisms and risk of post-stroke depression. Our findings show no difference among the groups with regards genotype distribution of the rs7412 polymorphism. In contrast, APOe genotypes with rs429358-C alleles increased the risk of post-stroke depression. Further, the rs429358 polymorphism was associated with significantly decreased regional cerebral blood flow values in the left temporal lobe of post-stroke depression cases. Additionally, the rs429358 polymorphism was not only associated with depression severity, but with increasing serum levels of total cholesterol. These resuits suggest that the APOe rs429358 polymorphism is associated with increased risk of developing post-stroke depression, and that APOe rs429358-C allele genotypes may be detrimental to recovery of nerve function after stoke. Indeed, these findings provide clinical data for future post-stroke depression gene interventions.

关键词： nerve regeneration apolipoprotein e genetic polymorphism post-stroke depression risk regional resting-state cerebral blood flow rs429358 rs7412 cerebral infarction neural regeneration

apolipoprotein e gene polymorphism in cerebrovascular diseases of the Chinese Naxi populations from Yunnan province

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Neural Regeneration Research 2011年第9期6卷 712-716页

作者： Hong Xu Qihong Yuan Xijun Fan Guoqiang He Department of Neurology First Affiliated Hospital of Kunming Medical College Kunming 650032 Yunnan Province China Department of Neurology First People's Hospital of Lijiang Lijiang 671000 Yunnan Province China

Currently it is not well known whether apolipoprotein e （Apoe） is a genetic susceptibility factor for cerebrovascular diseases in the Chinese Naxi population. The present study detected and sequenced Apoe polymorphisms of 90 patients with cerebrovascular diseases （58 cases of cerebral infarction and 32 cases of intracerebral hemorrhage）, and 50 normal people of Naxi nationality from Yunnan province, China. The populations were used to analyze the relationship of Apoe polymorphisms with cerebral infarction and intracerebral hemorrhage. Results showed an association between Apoe gene polymorphism and the onset of cerebral infarction, and a possibility that the ε4 allele is a susceptibility locus for the risk of cerebral infarction. However, there was no evidence of a relationship between the Apoe gene polymorphism and cerebral hemorrhage.

关键词： apolipoprotein e gene polymorphism cerebrovascular disease cerebral infarction intracerebral hemorrhage

apolipoprotein e gene polymorphism and susceptibility to intracerebral hemorrhage:A meta-analysis

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Neural Regeneration Research 2009年第1期4卷 58-61页

作者： Bo Peng Weifu Chen Zongyi Xie Yuan Cheng Department of Neurosurgery Second Affiliated Hospital of Chongqing Medical University Chongqing 400010 China

OBJeCTIVe： To evaluate the relationship between apolipoprotein e （Apoe） gene polymorphism and susceptibility to intracerebral hemorrhage （ICH） in Chinese population by a meta-analysis. MeTHODS： Related literature regarding control analysis between ICH and control groups was collected. Independent case-control studies published between 1989 and 2007 that had complete data were included; and articles not closely related to the topic were excluded. The meta-analysis software, RevMan 4.2, was applied to analyze the odds ratio （OR） value in those studies included in the analysis to assess the relationship between susceptibility to ICH and Apoe polymorphism. ReSULTS： eight papers which were in accordance with the inclusion criteria were selected, and a total of 1 249 ICH cases and 1 329 controls were involved. Meta-analysis results showed that with the wildtype e3/3 as a reference, the OR values （95% confidence interval） of intracerebral hemorrhage for subjects carrying e2/2, e3/2, e4/2, e4/3, and e4/4 were 1.15 （0.60–2.21）, 1.00 （0.79–1.28）, 3.01 （1.73–5.23）, 1.78 （1.41–2.24） and 1.94 （1.03–3.65）, respectively. The combined OR values （95% confidence interval） of intracerebral hemorrhage for ε4 and ε2 carriers were 1.53 （1.16–2.01）, and 0.93 （0.69–1.25）. CONCLUSION： The results suggest that Apoe polymorphism is significantly associated with susceptibility to intracerebral hemorrhage and that ε4 carriers have a higher risk for intracerebral hemorrhage than others.

关键词： apolipoprotein e intracerebral hemorrhage gene polymorphism Meta-analysis

apolipoprotein e polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis

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World Journal of Gastroenterology 2021年第11期27卷 1064-1075页

作者： José Carlos Rodrigues Nascimento Lianna C Pereira Juliana Magalhães C Rêgo Ronaldo P Dias Paulo Goberlânio B Silva Silvio Alencar C Sobrinho Gustavo R Coelho Ivelise Regina C Brasil edmilson F Oliveira-Filho James S Owen Pierluigi Toniutto Reinaldo B Oriá Department of Anesthesia and Surgery Liver Transplantation Fortaleza General HospitalFortaleza 60150-160CEBrazil Laboratory of the Biology of Tissue Healing Ontogeny and NutritionDepartment of Morphology and Institute of BiomedicineSchool of MedicineFederal University of CearáFortaleza 60430-270CEBrazil Department of Dental Clinic Federal University of CearáFortaleza 60430-270CEBrazil Department of Surgery Liver Transplant Unit of Federal University of CearáFortaleza 60430-270CEBrazil Transplantation Division Hospital Geral de FortalezaFortaleza 60175-742CEBrazil Institute of Virology CharitéUniversitätsmedizin BerlinBerlin 10117Germany UCL Medical School Royal Free CampusLondon NW32PFUnited Kingdom Department of Specialized Medicine Hepatology Liver Transplantation UnitAzienda Sanitaria Universitaria Integrata of UdineUdine I-33100Italy

BACKGROUND Hepatitis C virus(HCV)infection is responsible for a chronic liver inflammation,which may cause end-stage liver disease and hepatocellular *** e(protein:Apoe,gene:APOe),a key player in cholesterol metabolism,is mainly synthesized in the liver and APOe polymorphisms may influence HCV-induced liver *** To determine whether APOe alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation(OLT).MeTHODS This was a cohort study in which 179 patients,both genders and aged 34-70 years,were included before or after(up to 10 years follow-up)*** injury severity was assessed using different criteria,including MeTAVIR and models for endstage liver *** polymorphisms were analyzed by quantitative real-time polymerase chain *** The APOe3 allele was the most common(67.3%).In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant,the degree of severe inflammation(A3F4,0.0%)was significantly less frequent than in patients with minimal and moderate degree of inflammation(≤A2F4,16.2%)P=0.048,in patients carrying the APOe4 allele when compared to *** addition,a significant difference was also found(≤A2F4,64.4%vs A3F4,0.0%;P=0.043)and(A1F4,57.4%vs A3F4,0.0%;P=0.024)in APOe4 patients when compared to APOe3 *** fibrosis degree of the liver graft in 8 of 91 patients and the lack of the e4 allele was associated with more moderate fibrosis(F2)(P=0.006).CONCLUSION Our results suggest that the e4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.

关键词： apolipoprotein e Polymorphism Liver cirrhosis Hepatitis C virus Hepatocellular carcinoma Liver transplantation

Association of apolipoprotein e-219T>G promoter polymorphism with primary open angle glaucoma in Turkish population

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International Journal of Ophthalmology(english edition) 2014年第3期7卷 426-430页

作者： emel Saglar Banu Bozkurt Murat Irkec Department of Molecular Biology Faculty of ScienceHacettepe University Department of Ophthalmology Selcuk University Faculty of Medicine Department of Ophthalmology Hacettepe University Faculty of Medicine

AIM:To investigate the association between apolipoprotein e(APOe)-219 T>G promoter polymorphism and primary open angle glaucoma(POAG).MeTHODS:Patients and healthy subjects were genotyped with polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Genotype/allele frequencies were compared between 122 healthy subjects and in 75 POAG patients using Chi-square ***:Although the frequency of APOe-219 GG genotype was higher in POAG group(13.3%)than in control group(6.6%),this finding was not statistically significant(P=0.09).In glaucoma patients carrying GG genotype,mean linear C/D ratio was higher and progression was more compared to glaucoma patients with GT ***:APOe-219 T>G polymorphism does not seem to be a risk factor for the presence of glaucoma,but might play a role in deterioration of the disease,which needs further evaluation.

关键词： apolipoprotein e primary open angle glaucoma promoter single nucleotide polymorphism

Recombinant Neural Protein PrP Can Bind with Both Recombinant and Native apolipoprotein e In Vitro

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Acta Biochimica et Biophysica Sinica 2006年第9期38卷 593-601页

作者： Chen GAO~1 Yan-Jun LeI~(1,2) Jun HAN~1 Qi SHI~1 Lan CHeN~(1,3) Yan GUO~(1,4) Yong-Jun GAO~1 Jian-Ming CHeN~1 Hui-Ying JIANG~1 Wei ZHOU~1 Xiao-Ping DONG~1* 1 State Key Laboratory for Infectious Disease Prevention and Control,National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention,Beijing 100052,China 2 School of Medicine,Xi'an Jiaotong University,Xi'an 710061,China 3 National Laboratory of Medical Molecular Biology,Institute of Basic Medical Science,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China 4 College of Science and Veterinary Medicine,Northwest Agriculture and Forest University,Yangling 712100,China State Key Laboratory for Infectious Disease Prevention and Control National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 100052 China School of Medicine Xi'an Jiaotong UniversityXi'an 710061 China National Laboratory of Medical Molecular Biology Institute of Basic Medical Science Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005 China College of Science and Veterinary Medicine Northwest Agriculture and Forest UniversityYangling 712100 China

The most essential and crucial step during the pathogenesis of transmissible spongiformencephalopathy is the conformational change of cellular prion protein （PrPC） to pathologic isoform (PrPSc).Alot of data revealed that caveolae-like domains （CLDs） in the cell surface were the probable place where theconversion of PrP proteins *** e （Apoe） is an apolipoprotein which is considered toplay an important role in the development of Alzheimer's disease and other neurodegenerative diseases byforming protein complex through binding to the receptor located in the clathrin-coated pits of the cell *** this study,a 914-bp cDNA sequence encoding human Apoe3 was amplified from neuroblastoma cell *** human Apoe isomers were expressed and purified from escherichia ***-specificantiserum was prepared by immunizing rabbits with the purified ***/His pull-down assay,immunoprecipitation and eLISA revealed that three full-length Apoe isomers interact with the recombinantfull-length PrP protein in *** regions corresponding to protein binding were mapped in the N-terminalsegment of Apoe （amino acid 1-194） and the N-terminal of PrP （amino acid 23-90）.Moreover,the recombinantPrP showed the ability to form a complex with the native Apoe from liver *** data provided directevidence of molecular interaction between Apoe and *** also supplied scientific clues for assessing thesignificance of CLDs on the surface of cellular membrane in the process of conformational conversion fromPrPCto PrPScand probing into the pathogenesis of transmissible spongiform encephalopathy.

关键词： prion disease PrP apolipoprotein e protein interaction caveolae-like domain

apolipoprotein e GeNe POLYMORPHISMS AND RISK FOR CORONARY ARTeRY DISeASe IN CHINeSe XINJIANGUYGUR AND HAN POPULATION

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Chinese Medical Sciences Journal 2004年第2期19卷 150-154页

作者： Sheng-liYang Bing-xianHe Hui-liangLiu Zuo-yunHe HuaZhang Jian-pingLuo Xiu-fangHong Yang-chunZou DepartmentofCardiology GeneralHospitalofChinesePeople＇sArmedPoliceForcesBeijing100039 DepartmentofCardiology FirstAffiliatedHospitalofXinjiangMedicalUniversityUrumqi830054 DepartmentofCardiology XinqiaoHospitalThirdMilitaryMedicalUniversityChongqing400037

Objective To examine the relationship between apolipoprotein e (Apo e) gene polymorphism and risk of coronary artery disease (CAD), analyzing association of polymorphism with classical risk factors. Methods A total of 124 patients (including 84 Han population and 40 Uygur population) with angiographically verified CAD or myocardial infarction were prospectively evaluated. Data referring to hypertension, diabetes, and tobacco consump-tion were recorded. The levels of total cholesterol (TC), high density lipoprotein (HDL) cholesterol, Apo A1 and B, and triglycerides (TG) were determined. DNA was obtained from 124 patients and 70 controls. In order to determine Apo e genotypes, DNA was PCR amplified and digested with HhaI. The genetic polymorphism of Apo e is due to three common alleles, epsilon(ε) 2, ε3, ε4, at a single autosomal gene locus. These alleles determine the six phenotypes e2/2, e3/3, e4/4, e4/2, e4/3, and e3/2. Results In Uygur population, the frequency of the ε2, ε3, and ε4 was 0.155, 0.648, and 0.197 respectively. In Han po-pulation, the frequency of the ε2, ε3, and ε4 was 0.081, 0.772, and 0.146 respectively. In the patient group, the frequency of the ε2, ε3, and ε4was 0.060, 0.758, and 0.182 respectively. In the control group, the frequency of the ε2, ε3, and ε4 was 0.193, 0.671, and 0.136 respectively. ε2 frequency of Uygur’ patients and controls was 0.050 and 0.290 respectively. Serum low density lipoprotein (LDL) cholesterol, TC, and TG values tended to decrease from the Apo e-4 phenotypes to Apo e-2 phenotypes. When deletion polymorphism of ε2 was compared with the common risk factors for CAD, its risk ratio (RR) is 4.38. Conclusions These studies confirm and find that Apo e phenotype distribution in Uygur population differs significantly from that in Han population in Xinjiang. CAD patients have significantly lower ε2 allele and slightly higher ε3 or ε4 allele frequency than controls, especially in Uygur population. It shows protective effects of

关键词： apolipoprotein e DNA polymorphisms risk factors coronary artery disease

apolipoprotein e polymorphism in northern Chinese elderly patients with coronary artery disease

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Journal of Geriatric Cardiology 2006年第2期3卷 95-98页

作者： Yangchun ZOU Dayi HU Xiufang HONG Xingyuan JIA Xinchun YANG Liang CUI Heart and Basic Medical Center Chaoyang HospitalCapital University of Medical ScienceBeijing 100020China Department of Cardiology Affiliated Renmin HospitalPeking UniversityBeijing 100044China Department of Cardiology First Affiliated HospitalXinjiang Medical UniversityWulumuqi 830054China

Background and objective apolipoprotein e is a constituent of lipoproteins with considerable variation due to cysteine-arginine *** investigated the relationship between apo e gene polymorphism and the occurrence of coronary artery disease(CAD)in the older population of northern *** The distribution of the HhaI polymorphisms of the apolipoprotein e gene was determined among 55 patients with CAD(CAD group),which was compared with that of 36 elderly subjects without CAD(control group).Results Genotype distributions at both sites(apo e gene 112-bp and 158-bp sites)were different between the CAD and control *** CAD group had lower apolipoprotein e'ε2'frequencies than the control group(Papolipoprotein e'ε_(2)'are likely to have a reduced risk of developing coronary artery disease as demonstrated by elderly subjects in Northern China.

关键词： apolipoprotein e DNA-polymorphism elderly coronary artery disease