• Title/Summary/Keyword: Amyloid protein

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The Effect of Dodamtang(DDT) on Brain damage and Hypertension (도담탕(導痰湯)이 뇌손상(腦損傷) 및 고혈압(高血壓)에 미치는 영향(影響))

  • Lim, Seong-Min;An, Joung-Jo;Choi, Young;Kim, Yong-Jin;Yoo, Ho-Ryoung;Park, Yang-Chun;Seol, In-Chan;Hwang, Chi-Won;Cho, Hyun-Kyung
    • The Journal of Internal Korean Medicine
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    • v.22 no.4
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    • pp.503-512
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    • 2001
  • Objective : This study was carried out to investigate the effects of DDT on the brain damage and hypertension. Methods : We observed the effect of Dodamtang(DDT) extract on KCN-induced coma, focal brain ischemia by MCA occlusion, cytotoxicity and protection of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35). To prove the effect of DDT as a blood pressure depressant, we measured aldosterone, renin activity, catecholamine, sodium and NO density using the seperated blood plasma. Results : DDT showed a protective effect on cytotoxicity of PC12 cells and B103 cells induced by amyloid ${\beta}$ protein(25-35) in a dose dependent manner and proved the significant abridgement of brain ischemic area and edema induced by MCA occlusion, a critical decrease of neurologic deficitic grade in the fore-limbs. DDT didn't reduce the duration of KCN(1.87mg/kg iv.)-induced coma and prolonged the survival rate in the case of KCN(3.0mg/kg iv.)-induced coma by the ratio of 20%. While DDT increased the value of NO in SHR, it significantly decreased the blood pressure of SHR and the value of aldosterone& epinephrine in SHR. Conclusions : These results suggested that DDT might be usefully applied for treatment of hypertension, cerebral infarction, and brain damage.

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Effects of Posttraumatic Hypothermia in an Animal Model of Traumatic Brain Injury(TBI) - Immunohistochemical Stain by TUNEL & β-APP - (실험적 외상성 뇌손상모델에서 외상 후 저체온법의 효과 - TUNEL과 β-APP Immunohistochemical Stain -)

  • An, Byeong Kil;Ha, Young Soo;Hyun, Dong Keun;Park, Chong Oon;Kim, Joon Mee
    • Journal of Korean Neurosurgical Society
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    • v.29 no.4
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    • pp.461-470
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    • 2000
  • Objective : Many investigators have demonstrated the protective effects of hypothermia following traumatic brain injury(TBI) in both animals and humans. It has long been recognized that mild to moderate hypothermia improves neurologic outcomes as well as reduces histologic and biochemical sequelae after TBI. In this study, two immunohistochemical staining using terminal deoxynucleotidyl-transferase-mediated biotin dUTP nick end labeling(TUNEL), staining of apoptosis, and ${\beta}$-amyloid precursor protein(${\beta}$-APP), a marker of axonal injury, were done and the authors evaluated the protective effects of hypothermia on axonal and neuronal injury after TBI in rats. Material and Method : The animals were prepared for the delivery of impact-acceleration brain injury as described by Marmarou and colleagues. TBI is achieved by allowing of a weight drop of 450gm, 1 m height to fall onto a metallic disc fixed on the intact skull of the rats. Fourty Sprague-Dawley rats weighing 400 to 450g were subjected to experimental TBI induced by an impact-acceleration device. Twenty rats were subjected to hypothermia after injury, with their rectal temperatures maintained at $32^{\circ}C$ for 1 hour. After this 1-hour period of hypothermia, rewarming to normothermic levels was accomplished over 30-minute period. Following 12 hours, 24 hours, 1 week and 2 weeks later the animals were killed and semiserial sagittal sections of the brain were reacted for visualization of the apoptosis and ${\beta}$-APP. Results : The density of ${\beta}$-APP marked damaged axons within the corticospinal tract at the pontomedullary junction and apoptotic cells at the contused cerebral cortex were calculated for each animal. In comparison with the untreated controls, a significant reduction in ${\beta}$-APP marked damaged axonal density and apoptotic cells were found in all hypothermic animals(p<0.05). Conclusion : This study shows that the posttraumatic hypothermia result in substantial protection in TBI, at least in terms of the injured axons and neurons.

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Acute phase protein mRNA expressions and enhancement of antioxidant defense system in Black-meated Silkie Fowls supplemented with clove (Eugenia caryophyllus) extracts under the influence of chronic heat stress

  • Bello, Alhassan Usman;Sulaiman, Jelilat Aderonke;Aliyu, Madagu Samaila
    • Journal of Animal Science and Technology
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    • v.58 no.11
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    • pp.39.1-39.12
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    • 2016
  • Background: The current study investigates the anti-stress effects of clove (Eugenia caryophyllus) extracts (0, 200, 400, and 600 mg/kg) on serum antioxidant biomarkers, immune response, immunological organ growth index, and expression levels of acute phase proteins (APPs); ovotransferrin (OVT), ceruloplasmin (CP), ceruloplasmin (AGP), C-reactive protein (CRP), and serum amyloid-A (SAA) mRNA in the immunological organs of 63-d-old male black-meated Silkie fowls subjected to 21 d chronic heat stress at $35{\pm}2^{\circ}C$. Results: The results demonstrated that clove extract supplementation in the diet of Silkie fowls subjected to elevated temperature (ET) improve growth performance, immune responses, and suppressed the activities of glutathion peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and thioredoxin reductase (TXNRD); reduced serum malonaldehyde (MDA) and glutathione (GSH) concentrations when compared with fowls raised under thermoneutral condition (TC). Upon chronic heat stress and supplementation of clove extracts, the Silkie fowls showed a linear increase in GSH-Px, SOD, CAT, and TXNRD activities (P = 0.01) compared with fowls fed diets without clove extract. ET decreased (P < 0.05) the growth index of the liver, spleen, bursa of Fabricius and thymus. However, the growth index of the liver, spleen, bursa of Fabricius and thymus increased significantly (P < 0.05) which corresponded to an increase in clove supplemented levels. The expression of OVT, CP, AGP, CRP, and SAA mRNA in the liver, spleen, bursa of Fabricius and thymus were elevated (P < 0.01) by ET compared with those maintained at TC. Nevertheless, clove mitigates heat stress-induced overexpression of OVT, CP, AGP, CRP and SAA mRNA in the immune organs of fowls fed 400 mg clove/kg compared to other groups. Conclusions: The results showed that clove extracts supplementation decreased oxidative stress in the heat-stressed black-meated fowls by alleviating negative effects of heat stress via improvement in growth performance, antioxidant defense mechanisms, immunity, and regulate the expression of acute phase genes in the liver and immunological organs.

L-histidine and L-carnosine exert anti-brain aging effects in D-galactose-induced aged neuronal cells

  • Kim, Yerin;Kim, Yuri
    • Nutrition Research and Practice
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    • v.14 no.3
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    • pp.188-202
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    • 2020
  • BACKGROUND/OBJECTIVES: Brain aging is a major risk factor for severe neurodegenerative diseases. Conversely, L-histidine and L-carnosine are known to exhibit neuroprotective effects. The aim of this study was to examine the potential for L-histidine, L-carnosine, and their combination to mediate anti-brain aging effects in neuronal cells subjected to D-galactose-induced aging. MATERIALS/METHODS: The neuroprotective potential of L-histidine, L-carnosine, and their combination was examined in a retinoic acid-induced neuronal differentiated SH-SY5Y cell line exposed to D-galactose (200 mM) for 48 h. Neuronal cell proliferation, differentiation, and expression of anti-oxidant enzymes and apoptosis markers were subsequently evaluated. RESULTS: Treatment with L-histidine (1 mM), L-carnosine (10 mM), or both for 48 h efficiently improved the proliferation, neurogenesis, and senescence of D-galactose-treated SH-SY5Y cells. In addition, protein expression levels of both neuronal markers (β tubulin-III and neurofilament heavy protein) and anti-oxidant enzymes, glutathione peroxidase-1 and superoxide dismutase-1 were up-regulated. Conversely, protein expression levels of amyloid β (1-42) and cleaved caspase-3 were down-regulated. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-8, IL-1β, and tumor necrosis factor-α were also down-regulated. CONCLUSIONS: To the best of our knowledge, we provide the first evidence that L-histidine, L-carnosine, and their combination mediate anti-aging effects in a neuronal cell line subjected to D-galactose-induced aging. These results suggest the potential benefits of L-histidine and L-carnosine as anti-brain aging agents and they support further research of these amino acid molecules.

Therapeutic Effect of the Mixed Extract of Panax ginseng C.A. Mey. and Chaenomeles sinensis Koehne on the Injury of Brain Tissue in the Mice by Alzheimer's Disease (Alzheimer성 치매 유발 생쥐의 뇌조직 손상에 대한 인삼, 목과 혼합추출액의 치료 효과)

  • Han, Sin-Hee;Doh, Eun-Soo
    • Korean Journal of Plant Resources
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    • v.20 no.4
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    • pp.325-330
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    • 2007
  • This study was conducted to investigate the effect of the mixed extract of P. ginseng C.A. Mey. and C. sinensis K. (Gin-CHF) on the infarction area of hippocampus in the mice with Alzheimer's disease induced by ${\beta}-amyloid({\beta}A)$. The Gin-CHF extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. The Gin-CHF extract reduced the Tau protein, GFAP protein, and presenilin1/presenilin2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the Gin-CHF extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the Gin-CHF extract for Alzheimer's disease is suggested for further research.

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

  • Ro, Seung-Hyun;Ha, Nam-Chul
    • Journal of Life Science
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    • v.17 no.1 s.81
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    • pp.18-23
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    • 2007
  • Fe65, a neuron-specific adaptor protein, has two phosphotyrosine binding (PTB) domains. The second PTB (PTB2) domain interacts with intracellular domain fragment (AICD) of amyloid beta precursor protein (APP). Recent studies suggested that tile complex is composed of AICD and Fe65 transactivates genes that are responsible for neuronal cell death in Alzheimer's disease (AD). Therefore, a compound inhibiting the interaction between Fe65 and AICD can be a drug candidate to treat AD. However, it remains unclear how Fe65 recognizes AICD at a molecular level. Here, we report high-level production of the PTB2 domain of Fe65 in the baculovirus system. We found that the baculovirus system is an efficient method to obtain the Fe65 PTB2 domain, compared with the bacterial and mammalian expression systems. The purified recombinant protein was used for crystallization to determine its crystal structure helping to understand the molecular mechanism of Fe65-dependent signaling and to design its inhibitors.

Cytoprotective Effects of Phaeophyta Extracts from the Coast of Jeju Island in HT-22 Mouse Neuronal Cells (제주 연안 갈조류 추출물의 신경세포 보호효과)

  • Shin, Dong-Bum;Han, Eun-Hye;Park, Sung-Soo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.2
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    • pp.224-230
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    • 2014
  • Marine algae have long been recognized as a health and beauty food, based on its anti-tumor, anti-inflammatory and anti-obesity activities. In this study, methanol extracts were prepared from 10 different phaeophyta, after which DPPH radical scavenging and cytoprotective activities of HT-22 cells against ${\beta}$-amyloid protein ($A{\beta}$), which has neurotoxic effects, were investigated. In DPPH experiments, Ecklonia cava and Ishige okamurai showed strong ROS scavenging activities, whereas eight other phaeophyta including Petalonia binghamiae (P. bin) showed weak ROS scavenging activities. To validate the cytoprotective effects of 10 different phaeophyta in $A{\beta}$-induced HT-22 cells, protein expression levels of APP, BACE1, iNOS, phosphorylated ERK1/2, phosphorylated p38 and phosphorylated JNK1/2 were determined along with MTT assay. In the MTT assay, P. bin showed the best effective cytoprotective activity at a concentrations of $25{\mu}g/mL$, whereas Sargassum confusum, Colpomenia sinuosa, Myelophycus simplex, and Sargassum hemiphyllum showed potential. Determination of protein expression levels related to $A{\beta}$-induced neurotoxicity in the five selected phaeophyta showed that P. bin inhibited BACE1 and iNOS expression in $A{\beta}$-induced HT-22 cells. These results indicate that the cytoprotective effects of P. bin are mediated by suppressing the pathways involving $A{\beta}$-induced ERK and p38 activation.

Spinosin Attenuates Alzheimer's Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity

  • Cai, Mudan;Jung, Inho;Kwon, Huiyoung;Cho, Eunbi;Jeon, Jieun;Yun, Jeanho;Lee, Young Choon;Kim, Dong Hyun;Ryu, Jong Hoon
    • Biomolecules & Therapeutics
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    • v.28 no.2
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    • pp.131-136
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    • 2020
  • Hippocampal synaptic dysfunction is a hallmark of Alzheimer's disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.

Seed-Conjugated Polymer Bead for ${\beta}2$-Microglobulin Removal at Neutral pH

  • Kim, Mi-Ra;Kang, Sung-Soo;Myung, Eun-Kyung;Ahn, Min-Koo;Choi, Jeong-Hyun;Paik, Seung-R.;Lee, Yoon-Sik
    • Journal of Microbiology and Biotechnology
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    • v.19 no.9
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    • pp.960-965
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    • 2009
  • ${\beta}2$-Microglobulin (${\beta}2m$) is known to be a major factor for dialysis-related amyloidosis. We have studied ${\beta}2m$ removal through an aggregation process, which was initiated by a ligand that could catch the ${\beta}2m$ monomer and promote its aggregation into fibril. As a ligand, we have prepared ${\beta}2m$ fibril fragments and used them as a seed. The seed was coupled to PEGylated-PS beads to remove the monomeric ${\beta}2m$ from solution. The ${\beta}2m$ seed-conjugated resin effectively adsorbed the ${\beta}2m$ monomers with a capacity of 3.6 mg/ml via promoting their aggregation into fibrils on the resin at pH 7.4.

The Effects of KongJin-Dan(KJD) on the Alzheimer's Disease Model Induced by CT105 (공진단(拱辰丹)이 CT105로 유도된 Alzheimer's disease 병태(病態)모델에 미치는 영향)

  • Chung, Dae-Kyoo;Hwang, Seon-Mi
    • Journal of Oriental Neuropsychiatry
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    • v.15 no.2
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    • pp.103-118
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    • 2004
  • Objective : This experiment was designed to investigate the effect of KongJin-dan(KJD) on the Alzheimer's disease. Method : The effects of KJD on $LI-1{\beta}$, IL-6, $TNF-{\alpha}$, amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 and THP-1 cell treated by CT105 and AChE activity, APP production of PC-12 cell lysate treated by CT105 were investigated, respectively. Results : 1. KJD suppressed $LI-1{\beta}$, IL-6, $TNF-{\alpha}$, APP, AChE, GFAP mRNA in THP-1 and PC-12 cell treated by CT105. 2. KJD suppressed AChE activity and production of APP significantly in cell lysate of PC-12 cell treated by CT105. Conclusions : This study shows that KJD might be usefully applied for prevention and treatment of Alzheimer's disease.

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