• Korean Journal of Biological Psychiatry
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• v.10 no.2
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• pp.97-106
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• 2003

Criticisms about amyloid cascade hypothesis of Alzheimer's disease(AD) are based on the findings, first, that the degree of dementia does not correlate with the number of plaques, and second, that the neurofibrillary tangle formation seems to predate plaque formation. In addition, neurofibrillary tangle counts correlate well with the degree of cognitive impairment. These findings suggest the independent importance of tau abnormality in AD research which is involved in the neurofibrillary tangle formation. Recently, tau pathology without amyloid deposits and mutations in tau protein gene were reported to be the major pathogenic mechanism in Pick's disease, progressive supranuclear palsy, corticobasal degeneration and FTDP-17(frontotemporal dementia and parkinsonism linked with chromosome 17). These data suggest that understanding the causes and consequences of tau dysfunction might give new clinical and therapeutic solutions to many known tauopathies.

• Korean Journal of Microbiology
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• v.32 no.1
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• pp.28-33
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• 1994

In normal cells tau protein is associated with axonal microtubules, whereas in Alxheimer's disease it is immobilized in the somatodendritic compartment of certain nerve cells as a major component of the paired helical filament. As a part of the study to analyze the nature of the paired helical filament (PHF) deposits and some related factors in brain, we have cloned and expressed a human tau gene cDNA in Escherichia coli to obtain the recombinant human tau protein in abundance.

• Development and Reproduction
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• v.21 no.4
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• pp.417-424
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• 2017

Alzheimer's disease (AD) is neurodegenerative disease, characterized by the progressive decline of memory, cognitive functions, and changes in personality. The major pathological features in postmortem brains are neurofibrillary tangles and amyloid beta ($A{\beta}$) deposits. The majority of AD cases are sporadic and age-related. Although AD pathogenesis has not been established, aging and declining mitochondrial function has been associated. Mitochondrial dysfunction has been observed in AD patients' brains and AD mice models, and the mice with a genetic defect in mitochondrial complex I showed enhanced $A{\beta}$ level in vivo. To elucidate the role of mitochondrial complex I in AD, we used SH-SY5Y cells transfected with DNA constructs expressing human amyloid precursor protein (APP) or human Swedish APP mutant (APP-swe). The expression of APP-swe increased the level of $A{\beta}$ protein in comparison with control. When complex I was inhibited by rotenone, the increase of ROS level was remarkably higher in the cells overexpressing APP-swe compared to control. The number of dead cell was significantly increased in APP-swe-expressing cells by complex I inhibition. We suggest that complex I dysfunction accelerate amyloid toxicity and mitochondrial complex I dysfunction in aging may contribute to the pathogenesis of sporadic AD.

• Journal of Microbiology and Biotechnology
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• v.17 no.12
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• pp.2027-2032
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• 2007

[ ${\alpha}$ ]-Synuclein is the major component of Lewy bodies and responsible for the amyloid deposits observed in Parkinson's disease. Ordered filamentous aggregate formation of the natively unfolded ${\alpha}$-synuclein was investigated in vitro with the periodic ultrasonication. The ultrasonication induced the fibrillation of ${\alpha}$-synuclein, as the random structure gradually converted into a ${\beta}$-sheet structure. The resulting fibrils obtained at the stationary phase appeared heterogeneous in their size distribution, with the average length and height of $0.28\;{\mu}m{\pm}0.21\;{\mu}m$ and $5.6\;nm{\pm}1.9\;nm$, respectively. After additional extensive ultrasonication in the absence of monomeric ${\alpha}$-synuclein, the equilibrium between the fibril formation and its breakdown shifted to the disintegration of the preexisting fibrils. The resulting fragments served as nucleation centers for the subsequent seed-dependent accelerated fibrillation under a quiescent incubation condition. This self-seeding amplification process depended on the seed formation and subsequent alterations in their properties by the ultrasonication to a state that accretes the monomeric soluble protein more effectively than their reassociation of the seeds back to the original fibrils. Since many neurodegenerative disorders have been considered to be propagated via the seed-dependent amyloidosis, this study would provide a novel aspect of the significance of the seed structure and its properties leading to the acce]erated amyloid formation.

• Journal of Nutrition and Health
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• v.28 no.8
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• pp.737-748
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• 1995

Osteoblast(OBL) cells were isolated from ICR Swiss neonatal mouse calvarial tissues and cultured in a CO2 incubator with minimum essential medium (MEM) containing 0.25g BSA. The cells were cultured for 7 days and were treated with bovine parathyroid hormone (bPTH, 1-34) and calcitonin(CT). Enzyme activities related to mineral metabolism and other biochemical actions within the bone cells including protein phosphorylation were investigated. In other experiments using cultured calvarial bone tissues, hormones were treated for 24, 48, 72 or 96 hours. The activities of $\beta$-glucuronidase enzymes involved in bone collagen synthesis and mineral deposits were increased by 8% with bPTH and were inhibited with CT treatment, while those were 67% increase treated with bPTH and CT together. On the other hand, alkaline phophatase(AP) activities were inhibited by PTH hormone at all the time courses observed. Protein phosphorylation reaction in OBL was mediated by bPTH, cAMP and ionized Ca. Phosphorylation was observed in different cell fractions including homogenate, membrane and cytosol. The number of proteins phosphorylated by PTH, cAMP, and Ca were 10, 5, and 9, respectively. Most of the protein kinases(PKs) were existed in cytosolic compartment. In membrane fractions, two bPTH-dependent-PKs (70K, 50K Da) were observed of which 70K Da protein was also Ca-dependent. Most of the cAMP-dependent PKs were regulated via bPTH. 70K, 50K, 5K, 19K, 16K, 10.5K phosphoproteins regulated by Ca share the same pathways as those by bPTH-dependent proteins. Ca seems to regulate PK activities differently from cAMP.

• Journal of Integrative Natural Science
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• v.9 no.3
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• pp.171-176
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• 2016

Rap1 is a key regulator of cell adhesion and migration. Although increasing evidence indicates that the Rap1 signaling pathway is involved in the process of bone remodeling, the mechanism by which Rap1 regulates osteoblastic differentiation and cell adhesion remains unknown. Here, we investigated the morphological characteristics and osteoblastic differentiation of cells expressing constitutively activated form of Rap1A (Rap1ACA) or Rap1 GTPase activating protein Rap1GAP and found that activated Rap1 induces osteoblastic differentiation and cell adhesion as well as cell spreading. When osteoblastic differentiation was induced, Rap1ACA cells showed considerably higher levels of calcium deposits than the wild-type and Rap1GAP-overexpressing cells did. Rap1ACA cells showed increased spreading and size, as well as strong cell adhesion and significantly decreased growth rates. F-actin staining using phalloidin revealed several thin thread-like filopodia around the protrusions in Rap1ACA cells, which possibly contribute to the increased cell adhesion.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5577-5582
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• 2014

Objective: To observe the effects of metastasis-associated tumor gene family 2 (MTA2) depletion on human breast cancer cell proliferation and metastasis. Methods: A short-hairpin RNA targeting MTA2 was chemically synthesized and transfected into a lentivirus to construct Lv-shMTA2 for infection into the MDA-MB231 human breast cancer cell line. At 48 hours after infection cells were harvested and mRNA and protein levels of MTA2 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Cell viability and metastasis were assessed by CCK-8, wound-healing assay and Transwell assay, respectively. In addition, a xenograft model of human breast cancer was constructed to investigate cancerous cell growth and capacity for metastasis. Results: After infection with Lv-shMTA2, mRNA and protein levels of MTA2 was significantly reduced (p<0.05) and MDA-MB231 cell proliferation and metastasis were inhibited (p<0.05). In addition, mean tumor size was smaller than that in control group nude mice (p<0.05) and numbers of metastatic deposits in lung were lower than in control group mice (p<0.05). Depletion of MTA2 affected MMP-2 and apoptosis-related protein expression. Conclusions: For the first time to our knowledge we showed that MTA2 depletion could significantly inhibit human breast cancer cell growth and metastasis, implying that MTA2 might be involved in the progression of breast cancer. The role of MTA2 in breast cancer growth and metastasis might be linked with regulation of matrix metalloproteinase and apoptosis.

• Restorative Dentistry and Endodontics
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• v.39 no.3
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• pp.187-194
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• 2014

Objectives: The effects of bone morphogenetic protein-2 (BMP-2) and enamel matrix derivative (EMD) respectively with mineral trioxide aggregate (MTA) on hard tissue regeneration have been investigated in previous studies. This study aimed to compare the osteogenic effects of MTA/BMP-2 and MTA/EMD treatment in MC3T3-E1 cells. Materials and Methods: MC3T3-E1 cells were treated with MTA (ProRoot, Dentsply), BMP-2 (R&D Systems), EMD (Emdogain, Straumann) separately and MTA/BMP-2 or MTA/EMD combination. Mineralization was evaluated by staining the calcium deposits with alkaline phosphatase (ALP, Sigma-Aldrich) and Alizarin red (Sigma-Aldrich). The effects on the osteoblast differentiation were evaluated by the expressions of osteogenic markers, including ALP, bone sialoprotein (BSP), osteocalcin (OCN), osteopontin (OPN) and osteonectin (OSN), as determined by reverse-transcription polymerase chain reaction analysis (RT-PCR, AccuPower PCR, Bioneer). Results: Mineralization increased in the BMP-2 and MTA/BMP-2 groups and increased to a lesser extent in the MTA/EMD group but appeared to decrease in the MTA-only group based on Alizarin red staining. ALP expression largely decreased in the EMD and MTA/EMD groups based on ALP staining. In the MTA/BMP-2 group, mRNA expression of OPN on day 3 and BSP and OCN on day 7 significantly increased. In the MTA/EMD group, OSN and OCN gene expression significantly increased on day 7, whereas ALP expression decreased on days 3 and 7 (p < 0.05). Conclusions: These results suggest the MTA/BMP-2 combination promoted more rapid differentiation in MC3T3-E1 cells than did MTA/EMD during the early mineralization period.

• Journal of Yeungnam Medical Science
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• v.15 no.2
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• pp.359-370
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• 1998

Eight cases of chonproblastoma were studied by analyzing the clinical and pathologic findings. The age of eight cases ranged from 17 to 38 years old(median age, 22.7 years old). The tumors developed in the femur(3 cases), patella(2 cases), tibia(1 case), fibula(l case), and ulna(1 case). The mean diameter of tumors was 4.0cm (range, 1.5 to 8.0cm). Grossly, tumors showed grayish brown solid area with foci of secondary aneurysmal bone cyst. Histologically, the tumor cells were round or polygonal in shape with nuclear groove. And there were chondroid differentiation(7 cases), mitosis(3 cases), calcific deposits(3 cases), secondary aneurysmal bone cyst(4 cases), hemosiderin deposits(4 cases), necrosis(3 cases), vascular invasion(1 caes), and foamy histiocytes and cholesterol cleft(l cases). All cases showed no metastasis to lymph node and distant organ. Seven cases (87.5%) were immunoreactive for S-100 protein. None was immunoreactive for cytokeratin.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.1053-1057
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• 2012

Objective: Identifying cancer-related genes or proteins is critical in preventing and controlling colorectal cancer (CRC). This study was to investigate the clinicopathological and prognostic value of activating transcription factor 1 (ATF1) in CRC. Methods: Protein expression of ATF1 was detected using immunohistochemistry in 66 CRC tissues. Clinicopathological association of ATF1 in CRC was analyzed with chi-square test or Fisher's exact test. The prognostic value of ATF1 in CRC is estimated using the Kaplan-Meier analysis and Cox regression models. Results: The ATF1 protein expression was significantly lower in tumor tissues than corresponding normal tissues (51.5% and 71.1%, respectively, P = 0.038). No correlation was found between ATF1 expression and the investigated clinicopathological parameters, including gender, age, depth of invasion, lymph node status, metastasis, pathological stage, vascular tumoral emboli, peritumoral deposits, chemotherapy and original tumor site (all with P > 0.05). Patients with higher ATF1 expression levels have a significantly higher survival rate than that with lower expression (P = 0.026 for overall survival, P = 0.008 for progress free survival). Multivariate Cox regression model revealed that ATF1 expression and depth of invasion were the predictors of the overall survival (P = 0.008 and P = 0.028) and progress free survival (P = 0.002 and P = 0.005) in CRC. Conclusions: Higher ATF1 expression is a predictor of a favorable outcome for the overall survival and progress free survival in CRC.