• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.2
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• pp.186-193
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• 2007

The prevalence of diabetes has increased to 8% of population. Unlike type 2 diabetes in the western countries, Korean diabetic patients are nonobese and have low serum insulin levels. As the increased prevalence of diabetes and the peculiar characteristics may be related to dietary fat contents, we determined their effects on insulin resistance, insulin secretion and pancreatic $\beta-cell$ mass in 90% pancreatectomized (Px) diabetic rats in the present study. The rats were provided with low fat diet (LF, 10 energy% fat), moderate fat diet (MF, 25 energy% fat) and high fat diet (HF, 40 energy% fat) for 6 months. HF increased body weight and epidydimal fat pads parallel with increased food intake compared to LF and MF. Fasting serum glucose and insulin levels and homeostasis model assessment of insulin resistance were higher in HF, compared to LF and MF, indicating that HF increased insulin resistance. Rats fed LF and MF diets reduced insulin resistance, but only rats fed MF improved pancreatic $\beta-cell$ mass and insulin secretion capacity, measured by hyperglycemic clamp and in situ pancreatic perfusion. LF had low insulin secretion capacity and pancreatic $\beta-cell$ mass, indicating the increased possibility of diabetic prevalence and progression. MF increased $\beta-cell$ mass by stimulating $\beta-cell$ proliferation and neogenesis and reducing $\beta-cell$ apoptosis. In conclusion, MF is effective for the prevention of prevalence and progression of diabetes.

• YAKHAK HOEJI
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• v.52 no.1
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• pp.48-55
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• 2008

CD29 $({\beta}1-integrins)$ is one of major adhesion molecules involved in regulating cell adhesion, migration and morphological changes. In this study, we investigated the regulatory role of CD29 in monocytic functions using monocytic cell line U937 cells. CD29 was found to be one of highly expressed membrane proteins in U937 cells, according to flow cytometric analysis. The activation of CD29 by agonistic antibody MEM101A and extracellular matrix protein (ECM) fibronectin strongly induced cell-cell and cell-fibronectin adhesions. However, blocking antibodies to CD98 and CD147 showed different inhibitory features in these two adhesion events. Furthermore, U0126, an ERK inhibitor, only blocked cell-cell adhesion but not cell-fibronectin adhesion, indicating that cell-cell or cell-fibronectin adhesion events may be regulated by different molecular mechanisms. Meanwhile, CD29 activation also enhanced ROS generation but not phagocytic ability, and similarly radical scavenger N-acetyl-L-cysteine strongly blocked CD29-mediated cell-cell adhesion, implying that ROS may play a critical role in up-regulating cell-cell adhesion. Therefore, our data suggest that the activation of CD29 may be critically involved in regulating monocytic cell-mediated cell-cell adhesion and ROS generation.

• Animal cells and systems
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• v.4 no.4
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• pp.389-394
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• 2000

The Tcf-1 (1-cell factor-1) protein binds to the T-cell specific enhancer sequences and plays an architectural role in the assembly of transcriptional machinery. One of the Tcf family proteins, Tcf-4, was found to be an important regulator for colon cancer development where it activates specific genes upon binding to $\beta$-catenin following Wnt signaling. We were interested in the transcriptional regulatory activities of Tcf-1 and Tcf-4 proteins in T-cells and colon cancer cells. Transactivation assay was developed using a reporter plasmid containing luciferase gene under the control of Tcf responsive elements. Luciferase activity was determined following co-transfection of the reporter along with Tcf-1 and/or $\beta$-catenin expressing plasmids. Transcription was significantly induced by $\beta$-catenin expression in all cells. Tcf-1 by itself did not induce transcription in the mature T-cell lines, but overexpressed Tcf-1 greatly activated transcription in the immature T-cell line. In addition, transfected $\beta$-catenin induced apoptosis, but co-transfected Tcf-1 suppressed apoptosis in HEK293 cells. These results suggest that Tcf-1 and $\beta$-catenin differently regulate transcription and apoptosis.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.9-18
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• 2004

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of ${\beta}$-carbolines (harmaline and harmalol) and deprenyl on the dopamine-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. Cell death due to 250 4{\mu}$M dopamine was inhibited by caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk) and antioxidants (N-acetylcysteine, ascorbate, superoxide dismutase, catalase and carboxy-PTIO). ${\beta}$-Carbolines prevented the dopamine-induced cell death in PCl2 cells, while deprenyl did not inhibit cell death. ${\beta}$-Carbolines decreased the condensation and fragmentation of nuclei caused by dopamine in PC12 cells. ${\beta}$-Carbolines inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, formation of reactive oxygen species and depletion of GSH caused by dopamine in PC12 cells, whereas deprenyl did not decrease dopamine-induced mitochondrial damage. ${\beta}$-Carbolines, deprenyl and antioxidants depressed the formation of nitric oxide and melanin in dopamine-treated PC12 cells. The results suggest that cell death due to dopamine PC12 cells is mediated by caspase-8, -9 and -3. Unlike deprenyl, ${\beta}$-carbolines may attenuate the dopamineinduced cell death in PC12 cells by suppressing change in the mitochondrial membrane permeability through inhibition of the toxic action of reactive oxygen and nitrogen species.

• Tuberculosis and Respiratory Diseases
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• v.70 no.3
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• pp.206-217
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• 2011

Background: Transcription factor FOXP3 characterizes the thymically derived regulatory T cells. FOXP3 is expressed by cancer cell itself and FOXP3 expression was induced by TGF-${\beta}$ treatment in pancreatic cancer cell line. However, the expression of FOXP3 expression is not well known in patients with lung cancer. This study was conducted to investigate the expression of FOXP3 in patients with lung cancer and to investigate the regulation of FOXP3 expression by the treatment of TGF-${\beta}$ and DNA methyltransferase inhibitor in lung cancer cell lines. Methods: FOXP3 expression in the tissue of patients with resected non-small cell lung cancer (NSCLC) was evaluated by immunohistochemistry. The regulation of FOXP3 expression was investigated by Western blot and RT-PCR after lung cancer cell lines were stimulated with TGF-${\beta}1$ and TGF-${\beta}2$. The regulation of FOXP3 expression was also investigated by RT-PCR and flow cytometry after lung cancer cell lines were treated with DNA methyltransferase inhibitor (5-AZA-dC). Results: FOXP3 expression was confirmed in 27% of patients with NSCLC. In NCI-H460 cell line, TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. In A549 cell line, both TGF-${\beta}1$ and TGF-${\beta}2$ decreased FOXP3 mRNA and protein expressions. 5-AZA-dC increased FOXP3 mRNA expression in NCI-H460 and A549 cell lines. Moreover, 5-AZA-dC increased intracellular FOXP3 protein expression in A549 cell lines. Conclusion: It was shown that FOXP3 is expressed by cancer cell itself in patients with NSCLC. Treatment of TGF-${\beta}2$ and DNA methyltransferase inhibitor seems to be associated with the regulation of FOXP3 expression in lung cancer cell lines.

• Animal cells and systems
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• v.4 no.3
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• pp.273-278
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• 2000

Transforming growth factor-$\beta$ (IGF-$\beta$)s are multifunctional small polypeptides synthesized in most cell types. TGF-$\beta$ exerts pivotal effects on both bone formation and resorption. In addition, increasing lines of evidence implicate TGF-$\beta$ as a potential coupling factor between these two processes during bone remodeling. In the present study, the expression form and the activation mechanism of latent-TGF-$\beta$ were investigated using specific antibodies for each isoform. TGF-$\beta$s were observed to be synthesized and accumulated in a large amount in cultured osteoblastic cells. The estimated molecular weights of intracellular TGF-$\beta$2 and -$\beta$3 were 49 and 55 kDa, respectively. Based on proteolytic digestion study and immunofluorescence observation, these precursor forms seemed to be accumulated in distinct intracellular compartments. To examine whether the internal pool of TGF-$\beta$ was possiblely regulated by external signals, their biological activites were examined in a conditioned media of this cell. Although the intact conditioned media did not contain detectable TGF-$\beta$ activity, heat-treatment or acid-activation of the conditioned media revealed significant TGF-$\beta$ activity. Furthermore, in the presence of estrogen, this activity was dramatically diminished. It is known that activation of latent TGF-$\beta$ can be achieved by different chemical and enzymatic treatments, or by incubation with certain cell types. This extracellular activation was suggested as a key step in the regulation of TGF-$\beta$ activity. In addition to these extracellular activation, this study suggests that the synthesis and intracellular processing are important regulation steps for TGF-$\beta$ action. In addition, this regulation Is specific for TGF-$\beta$ type 2, because the change was not observed in TGF-$\beta$3 in osteoblastic cell line.

• KSBB Journal
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• v.11 no.4
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• pp.398-404
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• 1996

Escherichia coli was inoculated in calcium alginate capsules and cultivated to prepare encapsulated whole cell ${\beta}$-galactosidase. The dry cell weight in the capsule reached 100 g/L based on the inner space of the capsule. The activity of the encapsulated whole cell ${\beta}$-galactosidase increased with the dry cell weight increase during cultivation in the production medium. The activity of the encapsulated whole cell ${\beta}$-galactosidase was increased 25% by adding $2{\times}10^{-4}M Zn^{+2}$ ion in the production medium and 10% by coencapsulating with 2% (v/v) sunflower seed oil. The activity of encapsulated whole cell ${\beta}$-galactosidase produced in the concentric air lift reactor in which kLa was 82/hr was 86% higher than that in the shaking flask incubator where kLa was 2.55/hr.

• BMB Reports
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• v.40 no.6
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• pp.1058-1068
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• 2007

The post-translational modifications of Ser and Thr residues by O-linked $\beta$-N-acetylglucosamine (O-GlcNAc), i.e., O-GlcNAcylation, is considered a key means of regulating signaling, in a manner analogous to protein phosphorylation. Furthermore, it has been suggested that the increased flux of glucose through the hexosamine biosynthetic pathway (HBP) stimulates O-GlcNAcylation, and that this may be responsible for many of the manifestations of type 2 diabetes mellitus. To determine whether excessive O-GlcNAcylation of target proteins results in pancreatic $\beta$ cell dysfunction, we increased nucleocytoplasmic protein O-GlcNAcylation levels in $\beta$ cells by exposing them to streptozotocin and/or glucosamine. Streptozotocin and glucosamine co-treatment increased O-GlcNAcylated proteomic patterns as assessed by immunoblotting, and these increases in nuclear and cytoplasmic protein O-GlcNAcylations were accompanied by impaired insulin secretion and enhanced apoptosis in pancreatic $\beta$ cells. This observed $\beta$cell dysfunction prompted us to examine Akt and Bcl-2 family member proteins to determine which proteins are O-GlcNAcylated under conditions of high HBP throughput, and how these proteins are associated with $\beta$ cell apoptosis. Eventually, we identified ten new O-GlcNAcylated proteins that were expressed during $\beta$ cell apoptosis, and analyzed the functional implications of these proteins in relation to pancreatic $\beta$ cell dysfunction.

• YAKHAK HOEJI
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• v.36 no.5
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• pp.412-426
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• 1992

Effects of beta-carotene on the immunobiological responses were studied in ICR mice. ICR male mice were divided into 8 groups (10 mice/group), and beta-carotene at doses of 4, 20 and 100 mg/kg were orally administered to ICR mice once daily for 28 consecutive days. Cyclophosphamide (CY) was injected intraperitoneally (i.p.) to ICR mice with a single dose of 5 mg/kg body weight at 2 days before secondary immunization. Mice were sensitized and challenged with sheep red blood cells (5-RBC). Immune responses were evaluated by humoral immunity, cellular immunity and non-specific immunity. The results of this study were summarized as follows: (1) Beta-carotene significantly increased the weight ratios of liver, spleen and thymus to body weight depending on dose, and significantly increased the increasing rate of body weight and the number of circulating leukocyte. (2) Beta-carotene dose-dependently increased hemagglutination titer, Arthus reaction and hemolytic plaque forming cell related to humoral immunity. (3) Beta-carotene significantly increased delayed-type hypersensitivity reaction and rosette forming cell related to cellular immunity. (4) Beta-carotene dose-dependently increased phagocytic activity, and significantly increased natural killer (NK) cell activity. (5) Beta-carotene dose-dependently inhibited reductions in humoral immunity, cellular immunity, NK cell activity and phagocytic activity by treatment with CY.

• Journal of Oriental Neuropsychiatry
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• v.16 no.1
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• pp.81-96
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• 2005

This experiment was designed to investigate the effect of Dichroa febrifuga(DIF) on the Alzheimer’s disease. The effects of DIF extract on $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA of THP-1 cell treated by $A{\beta}$ plus LPS and amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. The results were summarized as follows ; 1. DIF extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$. 2. DIF extract suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. DIF extract suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. DIF extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. 5. DIF extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that DIF extract might be usefully applied for prevention and treatment of Alzheimer’s disease and memory deficit.