• 제목/요약/키워드: appA overexpression

검색결과 12건 처리시간 0.022초

조구등이 $\beta$APP 과발현 인간 신경아세포암에서의 항치매 효과에 관한 연구 (Study of Repair Effect of Anti-Alzheimer on $\beta$APP Overexpression In Neuroblastoma cell line by Ramulus et Uncus Uncariae)

  • 김상호;강형원;유영수
    • 동의생리병리학회지
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    • 제16권5호
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    • pp.960-966
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    • 2002
  • Ramulus et Uncus Uncariae (JGD) has sweet in flavour and slightly cold in property, acting on the liver and pericardium channels. This drug was described in a medical classic as having the ability to remove 'heat', check hyperfunction of the liver and relieve dizziness, tremors, and convulsions, and subdue 'endogenous wind'. So this study was estimated to check the anti-neuropathological effect of JGD on the Alzheimer in βAPP overexpression in neuroblastoma cell line and JGD extract was showed significantly anti-alzheimer effects (50 and 100 μg/㎖ of JGD extracts) compared with control group. Ramulus et Uncus Uncariae has anti-alzheimer effects on the βAPP overexpression in neuroblastoma cell line. So we expect that Ramulus et Uncus Uncariae may be used as a drug for neurodegenerative disease, such as stroke, Alzheimer's disease (AD). These results indicate that Ramulus et Uncus Uncariae possess strong inhibitory effect in the nervous system of apoptosis and repair effect against the degeneration of Neuroblastoma cells by βAPP expression.

향부자(香附子)가 치매병태모델에 미치는 영향(影響) (Effects of Cyperus rotundus (CPRT) on Inhibition of Impairment of Learning and Memory, and Acetylcholinesterase in Amnesia Mice)

  • 정인철;이상룡;윤상학
    • 동의신경정신과학회지
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    • 제14권1호
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    • pp.59-74
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    • 2003
  • Alzheimer's disease(AD) is a progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PS1 and PS2, and amyloid precursor proteins (APP) overexpression. The present research is to examine the inhibition effect of CPRT on PS-1, PS-2 and APP overexpression by detected to Western blotting. To verify the Effects of CPRT on cognitive deficits further, we tested it on the scopolamine-induced amnesia model of the mice using the Morris water maze tests, and there was ameliorative effects of memory impairment as a protection to scopolamine. CPRT only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine, whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracellular serum level compared with only scopolamine injection. In conclusion, studies of CPRT that has been known as anti-choline and inhibition ablilities of APP overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

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파극천(巴戟天)이 치매병태모델에 미치는 영향(影響) (Effects of Morinda officinalis (MDOF) on Inhibition of Impairment of Learning and Memory, and Acetylcholinesterase in Amnesia Mice)

  • 정인철;이상룡;김현수
    • 동의신경정신과학회지
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    • 제14권1호
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    • pp.45-58
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    • 2003
  • Alzheimer's disease(AD) is progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PS1 and PS2, and amyloid precursor proteins (APP) overexpression. The present research is to examine the inhibition effect of MDOF on PS-1, PS-2 and APP overexpression by detected to Western blotting. To verify the effects of MDOF on cognitive deficits further, we tested it on the scopolamine-induced amnesia model of the mice using the Morris water maze tests, and there was ameliorative effects of memory impairment as a protection to scopolamine. MDOF only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine, whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracelluar serum level compared with only scopolamine injection. In conclusion, studies of MDOF that has been know as anti-choline and inhibition ablilities of APP overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

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익정지황탕(益精地黃湯)이 치매병태(痴寐病態)모델에 미치는 영향(影響) (Effects of YkJungJiHwangTang(YJJHT) on Inhibition of Impairment of Learning and Memory, and Acetylcholinesterase in Amnesia Mice)

  • 최병만;이상룡
    • 동의신경정신과학회지
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    • 제11권2호
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    • pp.23-42
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    • 2000
  • Alzheimer's disease(AD) is progressive neurodegenerative disease, which is pathologically characterized by neuritic plaques and neurofibrillary tangles associated with the acetylcholinesterase, apolipoprotein E and butylcholinesterase, and by mutations in the presenilin genes PSI and PS2, and amyloid precursor proteins (APP) overexpression. The present research is to examine the inhibition effect of YJJHT on PS-1, PS-2 and APP overexpression by detected to Western blotting. To verify the EFFects of YJJHT on cognitive deficits further, we tested it on the scopolamine-induced amnesia model of the mice using the Morris water maze tests. and there was ameliorative effects of memory impairment s a protection to scopolamine. YJJHT only partially blocked the increase in blood serum level of acetylcholinesterase and Uric acid induced by scopolamine. whereas blood glucose level was shown to attenuate the amnesia induced by scopolamine and inreased extracellular serum level compared with only scopolamine injection. In conclusion, studies of YJJHT that has been know as anti-choline and inhibition ablilities of APP overexpression, this could also be used further as a important research data for a preventive and promising symptomatic treatment for Alzheimer's disease.

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MiR-144-3p and Its Target Gene β-Amyloid Precursor Protein Regulate 1-Methyl-4-Phenyl-1,2-3,6-Tetrahydropyridine-Induced Mitochondrial Dysfunction

  • Li, Kuo;Zhang, Junling;Ji, Chunxue;Wang, Lixuan
    • Molecules and Cells
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    • 제39권7호
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    • pp.543-549
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    • 2016
  • MicroRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. The present study focused on the role of hsa-miR-144-3p in one of the neuro-degenerative diseases, Parkinson's disease (PD). Our study showed a remarkable down-regulation of miR-144-3p expression in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated SH-SY5Y cells. MiR-144-3p was then overexpressed and silenced in human SH-SY5Y cells by miRNA-mimics and miRNA-inhibitor transfections, respectively. Furthermore, ${\beta}$-amyloid precursor protein (APP) was identified as a target gene of miR-144-3p via a luciferase reporter assay. We found that miR-144-3p overexpression significantly inhibited the protein expression of APP. Since mitochondrial dysfunction has been shown to be one of the major pathological events in PD, we also focused on the role of miR-144-3p and APP in regulating mitochondrial functions. Our study demonstrated that up-regulation of miR-144-3p increased expression of the key genes involved in maintaining mitochondrial function, including peroxisome proliferator-activated receptor ${\gamma}$ coactivator-$1{\alpha}$(PGC-$1{\alpha}$), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM). Moreover, there was also a significant increase in cellular ATP, cell viability and the relative copy number of mtDNA in the presence of miR-144-3p overexpression. In contrast, miR-144-3p silencing showed opposite effects. We also found that APP overexpression significantly decreased ATP level, cell viability, the relative copy number of mtDNA and the expression of these three genes, which reversed the effects of miR-144-3p overexpression. Taken together, these results show that miR-144-3p plays an important role in maintaining mitochondrial function, and its target gene APP is also involved in this process.

Effect of Transgenic Rhizobacteria Overexpressing Citrobacter braakii appA on Phytate-P Availability to Mung Bean Plants

  • Patel, Kuldeep J.;Vig, Saurabh;Nareshkumar, G.;Archana, G.
    • Journal of Microbiology and Biotechnology
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    • 제20권11호
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    • pp.1491-1499
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    • 2010
  • Rhizosphere microorganisms possessing phytase activity are considered important for rendering phytate-phosphorus (P) available to plants. In the present study, the Citrobacter braakii phytase gene (appA) was overexpressed in rhizobacteria possessing plant growth promoting (PGP) traits, for increasing their potential as bioinoculants. AppA was cloned under the lac promoter in the broadhost-range expression vector pBBR1MCS-2. Transformation of the recombinant construct pCBappA resulted in high constitutive phytase activity in all of the eight rhizobacterial strains belonging to genera Pantoea, Citrobacter, Enterobacter, Pseudomonas (two strains), Rhizobium (two strains), and Ensifer that were studied. Transgenic rhizobacterial strains were found to display varying levels of phytase activity, ranging from 10-folds to 538-folds higher than the corresponding control strains. The transgenic derivative of Pseudomonas fluorescens CHA0, a well-characterized plant growth promoting rhizobacterium, showed the highest expression of phytase (~8 U/mg) activity in crude extracts. Although all transformants showed high phytase activity, rhizobacteria having the ability to secrete organic acid showed significantly higher release of P from Ca-phytate in buffered minimal media. AppA overexpressing rhizobacteria showed increased P content, and dry weight (shoot) or shoot/ root ratio of mung bean (Vigna radiata) plants, to different extents, when grown in semisolid agar (SSA) medium containing Na-phytate or Ca-phytate as the P sources. This is the first report of the overexpression of phytase in rhizobacterial strains and its exploitation for plant growth enhancement.

Overexpression and Characterization of appA Phytase Expressed by Recombinant Baculovirus-Infected Silkworm

  • CHEN YIN;ZHU ZHONGZE;LIN XU'AI;YI YONGZHU;ZHANG ZHIFANG;SHEN GUIFANG
    • Journal of Microbiology and Biotechnology
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    • 제15권3호
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    • pp.466-471
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    • 2005
  • An Escherichia coli strain with high phytase activity was screened from pig excreta. The phytase gene, appA, was amplified by PCR technique. To obtain large amounts of appA phytase, the appA gene was subcloned into the baculovirus transfer vector pVL1393 under the control of the Polyhedrin promoter. The recombinant baculovirus harboring the appA gene was obtained after co-transfection and screening. The early $5^{th}$ instar larvae of silkworm were infected with the recombinant virus. Using this system, the appA phytase was overproduced up to 7,710 U per ml hemolymph. SDS-PAGE analysis revealed the baculovirus-derived appA phytase to be approximately 47 kDa in size. The optimal temperature and pH of the expressed phytase were $60^{\circ}C$ and pH 4.5, respectively. The enzymatic activity was increased by the presence of 1 mM $Ca^{2+}$, 1 mM $Mn^{2+}$, or $0.02\%$ Triton X-100.

Amyloid Precursor Protein Binding Protein-1 Is Up-regulated in Brains of Tg2576 Mice

  • Yang, Hyun-Jung;Joo, Yu-Young;Hong, Bo-Hyun;Ha, Sung-Ji;Woo, Ran-Sook;Lee, Sang-Hyung;Suh, Yoo-Hun;Kim, Hye-Sun
    • The Korean Journal of Physiology and Pharmacology
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    • 제14권4호
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    • pp.229-233
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    • 2010
  • Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer's disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer's disease.

BACE2의 대량발현 및 리폴딩 (Overexpression and Refolding of BACE2)

  • 박선주;타이슈아이치;이연지;전유진;김용태
    • 한국수산과학회지
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    • 제47권4호
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    • pp.370-375
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    • 2014
  • BACE2 is a membrane-bound aspartic protease that is highly homologous with BACE1. While BACE1 processes the amyloid precursor protein (APP) at a key step in generating ${\beta}$-amyloid peptide and presumably causes Alzheimer's disease (AD), BACE2 has not been demonstrated to be involved in APP processing directly, and its physiological functions are unknown. To determine its function and to develop inhibitors from marine sources, we constructed an overexpression vector for producing BACE2. The gene encoding human BACE2 protease was amplified using the polymerase chain reaction and cloned into the pET11a expression vector, resulting in pET11a/BACE2. Recombinant BACE2 protease was overexpressed successfully in E. coli as inclusion bodies, refolded using the rapid-dilution method, and purified via two-step fast protein liquid chromatography using Sephacryl S-300 gel filtration and Resource-Q column chromatography. The BACE2 protease produced was an active form. This study provides an efficient method not only for studying the basic properties of BACE2, but also for developing inhibitors from natural marine sources.

Fe65단백질의 한 PTB 도메인에 대한 과발현 및 초기 결정화 (High-level production and initial crystallization of a Fe65 PTB domain)

  • 노승현;하남출
    • 생명과학회지
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    • 제17권1호
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    • pp.18-23
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    • 2007
  • 신경세포에 특이적으로 발현되는 단백질인 Fe65는 두 개의 phosphotyrosine binding(PTB) 도메인을 가지고 있다. 두번째 PTB(PTB2)도메인은 아밀로이드 베타 전구 단백질(APP)의 세포질 도메인 조각(AICD)와 결합한다. 최근 연구 결과들은 AICD와 Fe65로 이루어진 결합체가 알츠하이머병에서 신경세포를 죽게 하는 유전자를 발현한다고 제시하고 있다. 따라서 Fe65와 AICD의 결합을 방해하는 화합물은 알츠하이머병을 치료하는데 후보물질이 될 수 있다. 하지만 AICD와 Fe65와 관련된 신호전달에 대한 분자적 기전은 잘 알려져 있지 않다. 이번 연구에서는 Fe65의 PTB2도메인을 baculovirus시스템에서 과발현시킨 결과를 보고한다. 세균 및 척추동물 세포를 이용한 시스템과 비교했을 때, baculovirus 시스템 이 훨씬 효과적 이 다는 것을 발견했다. 정제된 재조합 단백질을 이용하여 초기 결정을 얻었다. 결정을 이용하여 앞으로 밝힐 3차원 구조는 Fe65관련 신호전달체계에 대한 분자 기전 및 이에 대한 저해제 개발에 큰 도움을 줄 것이다.