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Presence of Transcription Factor OCT4 Limits Interferon-tau Expression during the Pre-attachment Period in Sheep

  • Kim, Min-Su;Sakurai, Toshihiro;Bai, Hanako;Bai, Rulan;Sato, Daisuke;Nagaoka, Kentaro;Chang, Kyu-Tae;Godkin, James D.;Min, Kwan-Sik;Imakawa, Kazuhiko
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.5
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    • pp.638-645
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    • 2013
  • Interferon-tau (IFNT) is thought to be the conceptus protein that signals maternal recognition of pregnancy in ruminants. We and others have observed that OCT4 expression persists in the trophectoderm of ruminants; thus, both CDX2 and OCT4 coexist during the early stages of conceptus development. The aim of this study was to examine the effect of CDX2 and OCT4 on IFNT gene transcription when evaluated with other transcription factors. Human choriocarcinoma JEG-3 cells were cotransfected with an ovine IFNT (-654-bp)-luciferase reporter (-654-IFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with Cdx2, Ets2 and Jun increased transcription of -654-IFNT-Luc by about 12-fold compared with transfection of the construct alone. When cells were initially transfected with Oct4 (0 h) followed by transfection with Cdx2, Ets2 and/or Jun 24 h later, the expression of -654-IFNT-Luc was reduced to control levels. OCT4 also inhibited the stimulatory activity of CDX2 alone, but not when CDX2 was combined with JUN and/or ETS2. Thus, when combined with the other transcription factors, OCT4 exhibited little inhibitory activity towards CDX2. An inhibitor of the transcriptional coactivator CREB binding protein (CREBBP), 12S E1A, reduced CDX2/ETS2/JUN stimulated -654-IFNT-Luc expression by about 40%, indicating that the formation of an appropriate transcription factor complex is required for maximum expression. In conclusion, the presence of OCT4 may initially minimize IFNT expression; however, as elongation proceeds, the increasing expression of CDX2 and formation of the transcription complex leads to greatly increased IFNT expression, resulting in pregnancy establishment in ruminants.

Effects of Ginseng Radix plus Crataegi Fructus on the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}$ amyloid peptide(${\beta}A$). (인삼산사복합방(人蔘山査複合方)이 Alzheimer성 치매 병태(病態) 생쥐의 뇌조직 손상에 미치는 효과)

  • Han, Sin-Hee;Kil, Gi-Jung
    • The Korea Journal of Herbology
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    • v.21 no.4
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    • pp.123-131
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    • 2006
  • Objectives : This research was investigated the effect of the Ginseng Radix plus Crataegi Fructus on the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. Methods : Observed a change of the injury of brain tissue and reduced the infarction area of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. Results : 1. The Gin-CF extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. 2. The Gin-CF extract reduced the Tau protein, GFAP protein, and presenilin1/presenilin2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusion : These results suggest that the Ginseng Radix plus Crataegi Fructus extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the Ginseng Radix plus Crataegi Fructus extract for Alzheimer's disease is suggested for future research.

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The Influence of Bakers' Yeast Cells on Protein Adsorption Performance in Dye-Ligand Expanded Bed Chromatography

  • Chow, Yen Mei;Tey, Beng Ti;Ibrahim, Mohd Nordin;Ariff, Arbakariya;Ling, Tau Chuan
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.10 no.6
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    • pp.552-555
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    • 2005
  • The influence of whole yeast cells $(0{\sim}15%\;w/v)$ on the protein adsorption performance in dye-ligand chromatography was explored. The adsorption of a model protein, bovine serum albumin (BSA), was selected to demonstrate this approach. The UpFront adsorbent $(p=1.5\;g/cm^3)$ derivatised with Cibacron Blue 3GA and a commercially available expanded bed column (20 mm i.d.) from UpFront Chromatography, Denmark, were employed in the batch binding and expanded bed operation. The BSA binding capacity was demonstrated to not be adversely affected by the presence of yeast cells. The dynamic binding capacity of BSA at a $C/C_0=0.1$ biomass concentration of 5, 10, 15% w/v were 9, 8, and 7.5mg/mL of settled adsorbent, respectively.

c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration

  • Ahn, Ji-Hwan;So, Sang-Pil;Kim, Na-Young;Kim, Hyun-Ju;Yoon, Seung-Yong;Kim, Dong-Hou
    • BMB Reports
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    • v.49 no.7
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    • pp.376-381
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    • 2016
  • Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer's disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD.

Ginsenoside Rg1 alleviates Aβ deposition by inhibiting NADPH oxidase 2 activation in APP/PS1 mice

  • Zhang, Han;Su, Yong;Sun, Zhenghao;Chen, Ming;Han, Yuli;Li, Yan;Dong, Xianan;Ding, Shixin;Fang, Zhirui;Li, Weiping;Li, Weizu
    • Journal of Ginseng Research
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    • v.45 no.6
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    • pp.665-675
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    • 2021
  • Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aβ) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aβ generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aβ deposition by inhibiting NOX2 activation in APP/PS1 mice.

The Effects of Daejo-hwan(DJR) on the Alzheimer's Disease Model Induced by ${\beta}$-amyloid. (대조환(大造丸) 추출물이 ${\beta}$-amyloid로 유도된 Alzheimer's disease 병태(病態)모델에 미치는 영향)

  • Lee, Ji-In;Chung, Dae-Kyoo
    • Journal of Oriental Neuropsychiatry
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    • v.18 no.3
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    • pp.55-82
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    • 2007
  • Ohjective: This research investigates the effect of the DJR on Alzheimer's disease. Method: 1.The effects of the DJR extract on IL.-$1{\beta}$, IL-6, TNF-${\alpha}$, cox-2, and NOS-II mRNA of BV2 microglia cell line treated with LPS; 2. the behavior: 3. the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}$A were investigated. Result: 1. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ mRNA in BV2 microglia cell line treated with LPS. 2. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ protein production in BV2 microglia cell line treated with LPS. 3. For the DJR extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by .${\beta}$A in the Moms water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The DJR extract suppressed the over-expression of IL-$1{\beta}$ protein, TNF-${\alpha}$ protein and CD68/CD11b, in the mice with Alzheimer's disease induced by ${\beta}$A 5. The DJR extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}$A. 6. The DJR extract reduced the tau protein, GFAP protein, and presenilin1/2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}$A. Conclusion: These results suggest that the DJR extract may he effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the DJR extract for Alzheimer's disease of suggested for future research.

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The Effect of Vitis labruscana B. Leaves Ethanol Extract on the Expression of Amyloid Precursor Protein in Neuroblastoma Cells and on the Acetylcholinesterase Activity (캠벨얼리(Vitis labruscana B.) 잎 에탄올 추출물이 신경세포에서 아밀로이드 전구 단백질의 발현과 아세틸콜린에스테라제 활성에 미치는 영향)

  • Choi, Ha Yeon;Kim, Ju Eun;Ma, Sang Yong;Cho, Hyung Kwon;Kim, Dae Sung;Leem, Jae Yoon
    • Korean Journal of Pharmacognosy
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    • v.53 no.2
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    • pp.102-110
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    • 2022
  • Alzheimer's disease (AD) is the most common form of dementia, and the accumulation of β-amyloid (Aβ) in the brain triggers AD, followed by hyperphosphorylation of tau protein, neurofibrillary tangles, and synapses loss, neuronal cell death, and cognitive decline occur in a chain. In APPswe neuronal cell line, 50 ㎍/ml of Campbell early (Vitis labruscana B.) leaves 50% ethanol extract (VLL) treatment inhibited the secretion of Aβ1-42 by about 63% and the secretion of Aβ1-40 by about 50%. VLL did not target the enzymatic activity of the amyloidogenic pathway and decreased the protein expression of APP. As a result of RT-qPCR (Reverse transcription-quantitative real-time PCR) of the APPswe cell line treated with VLL, it is thought that the protein expression of APP was reduced by inhibiting the transcription process of the APP gene. In addition, VLL inhibited acetylcholinesterase (AChE) enzyme activity in vitro by 27.6% and 54.7%, respectively, at 50 and 100 ㎍/ml concentrations. We found that VLL inhibited the production of Aβ, a dementia-inducing substance, by suppressing the transcription of the APP gene, and that VLL inhibited AChE activity. We suggest that VLL has the potential as a natural drug material that modulates the alleviation of dementia symptoms.

The Influence of Bakers' Yeast Cells on Protein Adsorption in Anion Exchange Expanded Bed Chromatography

  • Mei Chow Yen;Ti Tey Beng;Ibrahim Mohammad Nordin;Ariff Arbakariya;Chuan Ling Tau
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.10 no.3
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    • pp.280-283
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    • 2005
  • The adsorption of a model protein bovine serum albumin (BSA) in expanded bed chromatography was undertaken by exploiting a commercially available expanded bed column (20 mm i.d.) from UpFront Chromatography and Streamline DEAE $(\rho=1.2g/cm^3)$ from Amersham Pharmacia Biotechnology. The influence of whole yeast cells on the adsorption capacity of column was explored by employing yeast cells in a concentration ranged of 0 to $15\%(w/v)$. Equilibrium isotherms for adsorption of BSA on Streamline DEAE were correlated by using Langmuir equation. The presence of yeast cells resulted in decreased of BSA binding capacity in both batch binding and expanded bed chromatography. Results indicated that the yeast cells act as competitor for proteins to bind to the sites on adsorbents.

Development of Inhibitors of $\beta$-Amyloid Plaque Formation

  • Kim, Dong-Jin
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2006.04a
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    • pp.123-135
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    • 2006
  • Alzheimer's disease (AD) is the most common form of dementia in the aging population and is clinically characterized by a progressive loss of cognitive abilities. Pathologically, it is defined by the appearance of senile plaques - extracellular insoluble, congophilic protein aggregates composed of amyloid $\beta$ (A$\beta$) and neurofibrillary tangles (NFTs) - inyracellular lesions consisting of paired helical filaments from hyperphosphorylated cytoskeletal tau protein as described by Alois Alzheimer a century ago. These hallmarks still serve as the major criteria for a definite diagnosis of the disease. Consequently, one of the key strategy for drug development in this disease area focuses on reducing the concentration of cerebral A$\beta$ plaque by using substances that inhibit A$\beta$ fibril formation. We focused on developing inhibitors by synthesizing several kinds of aromatic molecules. The synthetic compounds were initially screened to evaluate the effective compound by tioflavin T fluorescence assay. The selected effective compounds were tested cytotoxicity and protective effect from A$\beta$-induced neuronal toxicity by cell based MTT assay with HT22 hippocampal neurons. The BBB permeability on effectors was also tested in in vitro co-culture model(HUVEC/C6 cell line). The behavior test wea carried out in mutant APP/PS1 transgenic mouse model of Alzheimer's disease. And inhibition of A$\beta$ fibril formation by the effective compound was monitored with transmitted electron microscopic images.

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Production of Hepatitis B Core Antigen in a Stirred Tank Bioreactor: The Influence of Temperature and Agitation

  • Tey, Beng Ti;Chua, Mung Ing;Chua, Ghee Sung;Ng, Michelle Yeen Tan;Biak, Dayang Radiah Awang;Tan, Wen Siang;Ling, Tau Chuan
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.2
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    • pp.164-167
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    • 2006
  • The influence of temperature and agitation on the growth of Escherichia coli expressing hepatitis B core antigen (HBcAg) in stirred tank bioreactor were investigated. The highest specific growth rate for E. coli$(0.844 h^{-1})$ was achieved at a temperature of $37^{\circ}C$ and an agitation speed of 250 rpm. The activation energy for the growth of the E. coli strain W3110lQ in the stirred tank bioreactor was estimated to be 11 kcal/mol. The highest protein yield was achieved at a temperature of $44^{\circ}C$ and an agitation speed of 250 rpm. The relative protein concentration at $44^{\circ}C$ is 30 and 6% higher compared to that at 30 and $37^{\circ}C$, respectively.