• Environmental Mutagens and Carcinogens
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• v.22 no.1
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• pp.39-46
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• 2002

Obesity is a complex metabolic disorder with a strong genetic component. There are many candidate genes for obesity and its related phenotypes. We studied genetic variations between Korean obese and lean groups. Polymorphisms investigated were the Msp I polymorphism of the $\alpha$$_{2A}$-adrenergic receptor ($\alpha$$_{2A}$-AR) gene, the Mnl I polymorphism of the $\alpha$$_2$-adrenergic receptor ($\alpha$$_2$-AR) gene, the BstO I polymorphism of the $\beta$$_3$-adrenergic receptor ($\beta$$_3$-AR) gene, the Pml I polymorphism of the lamin A/C (LMNA) gene, the Hga I polymorphism of the clearance receptor (NPRC) gene, the Msp I polymorphism of the leptin gene, BclI polymorphism of the uncoupling protein 1 (UCPI) gene and the Hha I polymorphism of the fatty acid binding protein 2 (FABP2) gene. Among these genetic markers, Pml I polymorphism at the LMNA gene and Bcl I polymorphism at the UCP1 gene were significantly associated with obesity. However, further studies are required whether thease findings are reproduced in large population, although two polymorphisms might be useful as genetic markers in the ethiology of obesity in Korean population.ion.

• Journal of Life Science
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• v.21 no.12
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• pp.1678-1688
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• 2011

The apoptogenic effect of p-coumaric acid, a phenolic acid found in various edible plants, on human acute leukemia Jurkat T cells was investigated. Exposure of Jurkat T cells to p-coumaric acid (50-$150{\mu}M$) caused cytotoxicity and TdT-mediated dUTP nick-end labeling (TUNEL)-positive apoptotic DNA fragmentation along with Bak activation, ${\Delta}{\psi}m$ loss, activation of caspase-9, -3, -7, and -8, and PARP degradation in a dose-dependent manner. However,these apoptotic events were completely abrogated in Jurkat T cells overexpressing Bcl-2.Under these conditions, necrosis was not accompanied. Pretreatment of the cells with the pan-caspase inhibitor (z-VAD-fmk) could prevent p-coumaric acid-induced sub-$G_1$ peak representing apoptotic cells, whereas it failed to block ${\Delta}{\psi}m$ loss, indicating that the activation of caspase cascade was prerequisite for p-coumaric acid-induced apoptosis as a downstream event of ${\Delta}{\psi}m$ loss. FADD- and caspase-8-positive wild-type Jurkat T cell clone A3, FADD-deficient Jurkat T cell clone I2.1, and caspase-8-deficient Jurkat T cell clone I9.2 exhibited similar susceptibilities to the cytotoxicity of p-coumaric acid, excluding an involvement of Fas/FasL system in triggering the apoptosis. The apoptogenic activity of p-coumaric acid is more potent in malignant Jurkat T cells than in normal human peripheral T cells. Together, these results demonstrated that p-coumaric acid-induced apoptogenic activity in Jurkat T cellswas mediated by Bak activation, ${\Delta}{\psi}m$ loss, and subsequent activation of multiple caspases such as caspase-9, -3, -7, and-8, and PARP degradation, which could be regulated by anti-apoptotic protein Bcl-2.

• The Journal of Korean Medicine
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• v.23 no.3
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• pp.145-163
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• 2002

Objectives: The purpose of this investigation was to evaluate the effects of Woohwangcheongsim-won and to study the mechanism for neuronal death protection in hypoxia with Embryonic day 20 (E20) cortical cells of a rat (Sprague Dawley). Methods: E20 cortical cells were dissociated in neurobasal media and grown for 14 days in vitro (DIV). On 14 DIV, Woohwangcheongsim-won was added to the culture media for 24 hrs or 72 hrs. On 17 DIV, cells were given a hypoxic shock and further incubated in normoxia for another three days. On 20 DIV, Woohwangcheongsim-won's effects for neuronal death protection were evaluated by LDH assay, propidium iodide stain and phospho-H2AX immunostain and the mechanisms were studied by Bcl-2, Bak, Bax, caspase family, PKCα, ca1pain I. Results & Conclusions : 1. This study indicated that Woohwangcheongsim-won's effects for neuronal death protection in hypoxia were confirmed by LDH assay, propidium iodide stain and phospho-H2AX immunostain in culture method of Embryonic day 20(E20) cortical neuroblasts. 2. Woohwangcheongsim-won's mechanisms for neuronal death protection in hypoxia are to reduce the membrane damage fraction, to restrain DNA truncate, to restrain inflow of cytochrome c into cellularity caused by Bak diminution, to reduce the caspase cascade intiator caspase-8 and the effector caspase-3, to reduce the calpain I activity and to increase PKCand its activity in the membrane fraction. (J Korean Oriental Moo 2002;23(3):145～163)

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.366-373
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• 2006

Background: Paraquat is extremely toxic chemical material, which generates reactive oxygen species (ROS), causing multiple organ failure. In particular, paraquat leads to irreversible progressive pulmonary fibrosis. Exaggerated cell deaths exceeding the normal repair of type II pneumocytes leads to mesenchymal cells proliferation and fibrosis. This study examined the followings; i) whether or not paraquat induces cell death in lung epithelial cells; ii) whether or not paraquat-induced cell deaths are apoptosis or necrosis; and iii) the effects of N-acetylcysteine, dexamethasone, and bcl-2 on paraquat-induced cell deaths. Methods: A549 and BEAS-2B lung epithelial cell lines were used. The cell viability and apoptosis were evalluated using a MTT assay, Annexin V staining was monitored by fluorescence microscopy, The level of bcl-2 inhibition was examined by establishing stable A549 pcDNA3-bcl-2 cell lines throung the transfection of pcDNA3-bcl-2 with the mock. Results: Paraquat decreased the cell viability in A549 and BEAS-2B cells in a dose and time dependent manner. The Annexin V assay showed that apoptosis was the type of paraquat-induced cell death. Paraquat-induced cell deaths was significantly inhibited by N-acetylcysteine, dexamethasone, and bcl-2 overexpression. The cell viability of A549 cells treated with N-acetylcysteine, and dexamethasone on the paraquat-induced cell deaths were increased significantly by 10 ~ 20%, particularly at high doses. In addition, the cell viability of A549 pcDNA3-bcl-2 cells overexpressing bcl-2 was significantly higher than the untransfected A549 cells. Conclusion: Paraquat induces apoptotic cell deaths in lung epithelial cells in a dose and time dependent manner. The paraquat-induced apoptosis of lung epithelial cells might occur through the mitochondrial pathway.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.1
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• pp.47-55
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• 2003

Objectives: Bok, Bcl-2-related ovarian killer, is a proapoptotic Bcl-2 family protein identified in the ovary based on its dimerization with the antiapoptotic protein Mcl-1. The present study examined the hormonal regulation and localization of Bok messenger RNA levels in the mouse ovary during the follicle development. Methods: The animals were implanted subcutaneously with Silastic brand capsules containing the synthetic estrogen, DES at $21{\sim}23$ days of age. Ovaries were collected $1{\sim}3$ days after implantation for RNA analysis and in situ hybridization. Some mice were removed capsule for $1{\sim}2$ days to induce ovarian follicle apoptosis. Ovaries were also collected from 26 day-old immature mice at various times after treatment with 10 IU PMSG. Some mice received a single intraperitoneal injection of 10 IU hCG to induce ovulation, and ovaries were obtained at different time intervals for Northern blot and in situ hybridization analysis, respectively. Results: Treatment of immature mice with diethylstilbestrol (DES) for $24{\sim}48$ h increased ovarian Bok mRNA levels. Bok mRNA was remained the same levels in mice removed DES for $24{\sim}48$ h to induce apoptosis. High signals of Bok mRNA after DES treatment were detected in granulosa cells of early antral follicles. Treatment of immature mice with PMSG for 12 h increased markedly ovarian Bok mRNA expression which was detected mainly in preantral and atretic follicles. Interestingly, low levels of Bok mRNA were also expressed in granulosa cells of preovulatory follicles. Treatment of PMSGprimed mice with hCG stimulated strongly ovarian Bok mRNA expression at $6{\sim}9$ h. At that time, Bok mRNA was expressed in granulosa cells of atretic and small growing follicles. Conclusion: These results demonstrate that Bok is one of proapoptotic Bcl-2 members expressed in early growing and atretic follicles during the ovarian follicular development. Gonadotropins induce a transient increase of Bok gene expression in granulosa cells of preantral and preovulatory follicles indicating some role in the ovulatory process.

• Journal of Life Science
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• v.14 no.3
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• pp.445-452
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• 2004

We investigated the cytotoxic effects of seven furanoterpenoids 〔sarcotin A, epi-sarcotin A, ircinin-1, epi-sarcotrine B, sarcotin I, (8E, l3Z, 20Z)-strobilinin/(7E,l3Z, 20Z)-felixinin and (7E,12E,18R,20Z)-variabilin〕 isolated from the sponge Sarcotragus sp. (the order Dictyoceratida) on the growth of A549 human lung carcinoma cells. MTT data revealed that sarcotin A and (7E,12E,18R,20Z)-variabilin exhibited higher potencies on the anti-proliferative activities than the other compounds in A549 cells. The growth inhibition by treatment with compounds (especially epi-sarcotin A, ircinin-1 and epi-sarcotrine B) were associated with the induction of apoptotic cell death through the concentration-dependent increase of Bax/Bcl-2 ratio in a p53-dependent or independent pathway Additionally, epi-sarcotin A and ircinin-1 strongly inhibited the levels of cyclooxygenase (COX)-2 expression without alteration of COX-1. Taken together, the results suggest that the furanoterpenoids from the marine sponge have strong potentials as candidates for anti-cancer drugs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.358-364
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• 2006

To investigate the possible mechanism of Drynariae Rhizoma extracts as a candidate of anti-cancer drug, I examined the effects of Drynariae Rhizoma extracts on the apoptosis of U937 cell line. MTT assay, flow cytometric analysis, SDS-polyacrylamide gel electrophoresis, Western blot analysis, and RT-PCR were performed. Drynariae Rhizoma extracts treatment reduced the cell viablilty of U937 cells in a dose-dependent manner, which was associated with induction of apoptotic cell death. Drynariae Rhizoma extracts treatment also reduced the levels of Bcl-xL anti-apoptotic protein expression and increased the levels of caspase-3, p53, pro-apoptotic protein, in U937 cells. RT-PCR data revealed that the level of bcl-2, bcl-xL mRNA expressions decreased in a dose-dependent manner. These findings suggest that Drynariae Rhizoma extracts may have induction of apoptotic cell death via regulation of several growth regulatory gene products. The abbreviations used are: FBS, fetal bovine serum; PBS, phosphate buffered saline; PI, propidium iodide; OD, optical density; DiOC6, 3,3-dihexyloxa carbcyanine iodide; MTT, 3 [4-5-dimethylthiazol-2-yl] -2-diphenyltetrazolium bromide.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.5
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• pp.710-719
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• 2001

Several amino acid transport systems in mammary gland have been characterized during the last few years. These systems may be divided into two broad categories based on whether they are sodium-dependent or $Na^{+}$-independent, and each of these categories is subdivided into 3 groups depending on whether the systems prefer zwitterionic, cationic or anionic substrates. The zwitterion preferring transport processes in mammary gland are $Na^{+}$-dependent system A and $Na^{+}$-independent systems L and T. System $y^{+}$ is a $Na^{+}$-independent transporter of cationic amino acids and $X_{AG^{-}}$ is a $Na^{+}$-dependent system for anionic amino acids. A ($Na^{+}+Cl^{-}$)-dependent system, selective for $\beta$-amino acids has been reported in rat mammary tissue. In addition, there is yet another class of transporters that have still broader specificity. The $Na^{+}$-dependent systems $BCl^{-}$-dependent and $BCl^{-}$-independent and $Na^{+}$-independent system $y^{+}L$ have been reported to mediate the transport of zwitterionic as well as cationic amino acids. Each system has been characterized with respect to its substrate specificity, affinity, kinetics and ion-dependence. Transport of amino acids by mammary tissue is regulated by i) the intracellular substrate concentration, ii) lactogenic hormones and iii) milk stasis. Four of the above transport systems (i.e. A, L, $y^{+}$ and $BCl^{-}$-independent) are up-regulated by lactogenic hormones (insulin, cortisol and prolactin) in mammary gland.

• Journal of Pharmacopuncture
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• v.21 no.3
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• pp.159-167
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• 2018

Objectives: Myocardial reperfusion is the only logical cure for ischemic heart disease. However, ischemic-reperfusion (I/R) injury is one of the underlying factors facilitating and accelerating the apoptosis in the myocardium. This study set to investigate the impact of Teucrium polium (TP) hydro-alcoholic extract on I/R induced apoptosis in the isolated rat heart. Methods: Isolated rat hearts were classified into six groups. The control samples were subjected to 80 min of perfusion with Krebs-Henseleit bicarbonate (KHB) buffer; in control-ischemia group, after primary perfusion (20 min) the hearts were exposed to global ischemia (20 min) and reperfusion (40 min). Pretreated groups were perfused with $500{\mu}M$ of vitamin C and various TP concentrations (0.5, 1, 2 mg/ml) for 20 min, and then the hearts were exposed to ischemia and reperfusion for 20 min and 40 min, respectively. Cardiodynamic parameters including rate pressure product (RPP), heart rate (HR), the maximum up/down rate of left ventricular pressure (${\pm}dp/dt$), left ventricular developed pressure (LVDP), and coronary artery flow (CF) were achieved from Lab Chart software data. The Bax and BCl-2 gene expressions were measured in heart samples. Results: Hearts treated with TP extract and vit C represented a meaningful improvement in cardiac contractile function and CF. The overexpression of Bcl-2, downregulation of Bax, and improvement of apoptotic index (Bax/Bcl-2) were observed in pretreated TP extract and vit C hearts. Conclusion: The TP extract was found to ameliorate the cardiac function in the reperfused myocardium. Also, it can hinder apoptotic pathways causing cardioprotection.

• The Journal of Korean Obstetrics and Gynecology
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• v.24 no.2
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• pp.13-32
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• 2011

Objectives: This study was performed to elucidate the effects of Danchisoyo-san (DS) on cell damage and gene expression in UVB-exposed dermal fibroblast. Methods: To demonstrate the inhibitory effects of DS on aging of the skin, we used human dermal fibroblast(F6) and UVB light(30 mJ/$cm^2$) was used to damage to dermal fibroblast. We measured the nitrite production, LDH release, and gene expression in UVB-irradiated dermal fibroblast to elucidate the actionmechanism of DS. Also, we evaluated the amount of increased PICP, TIMP-1 in dermal fibroblast. PICP, TIMP-1 concentration was measured using EIA kit, and gene expression (MMP-1, procollagen, c-fos, c-jun, NF-kB, Bcl-2, Bcl-xL, iNOS) were determined using real-time PCR. Results: 1. DS inhibited LDH-release, nitrite production in UVB-irradiated dermal fibroblast. 2. DS suppressed the gene expression of MMP-1 in UVB-irradiated dermal fibroblast. 3. DS increased the gene expression of procollagen in UVB-iradiated dermal fibroblast. 4. DS suppressed the gene expression of c-jun, c-fos, NF-kB, iNOS in UVBirradiated dermal fibroblast. 5. DS increased the gene expression of Bcl-2 in UVB-iradiated dermal fibroblast. 6. DS increased the cell proliferation of dermal fibroblast. Conclusions: From the results, we concluded DS increases the cell proliferation and collagen synthesis in dermal fibroblast. So we suggest that DS has the antiwrinkle effects.