• Journal of Life Science
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• 제29권11호
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• pp.1179-1191
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• 2019

Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.

• Journal of the Korean institute of surface engineering
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• 제29권3호
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• pp.195-202
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• 1996

The composition, the microstructure and the magnetic properties(HC and Hk) of Fe-Co-Ni alloy electrodeposits were investigated according to the electrolysis conditions using sulfate bath paddle agitated. The current efficiency of the alloys electrodeposition was considerably low in the range of 16∼50%. The Fe content(wt.%) of the alloy increased from 20% to 57% with current density, while Ni content of them decreased in the range of 70∼24% respectively, and Co content was nearly constant. As a result, Fe/Ni ratio of the alloy increased from 0.3 to 2.0 showing the anomalous codeposition. The structure of the alloy changed from fcc to the mixed one of fcc+bcc with the increase of Fe/Ni ratio. The preferred orientation of the alloy with fcc and bcc structure were (220) and (110) respectively. The alloy with Fe/Ni ratio(0.3∼l.2) had the lowest coercivity of 0.4∼0.8 Oe.

• Journal of Life Science
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• 제20권1호
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• pp.133-141
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• 2010

The protective effect of a mixed powder from solid-cultured and liquid-cultured Lentinus edodes mycelia (2:1, w/w) (designate LED) on the carbon tetrachloride ($CCl_4$)- and ethanol-induced hepatotoxicity of male Sprague-Dawley (SD) rat was investigated. In the $CCl_4$-induced rat hepatotoxicity experiment, rats of 4 groups (6 rats/group) were administere with Normal (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 200 mg/kg BW + 0.2 ml distilled water), and Silymarin (200 mg/kg BW + 0.2 ml distilled water), p.o., daily for 2 weeks. Afterwards, all groups except for the Normal group were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1:1 v/v; 0.5 ml/kg BW). For the ethanol- induced rat hepatotoxicity experiment, rats were divided into 5 groups (5 rats/group): Normal; Pair-fed control (PFC); Control (ethanol); LED (ethanol + LED 200 mg/kg BW); and Silymarin (ethanol + silymarin 200 mg/kg BW). Rats of the Normal and PFC groups were fed a basal liquid diet, and rats of the Control, LED, and Silymarin groups were fed a liquid ethanol diet containing LED or Silymarin. Eight weeks later, blood and liver samples were collected to analyze biomarkers. In $CCl_4$-induced SD rats, LED elevated hepatic superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH peroxidase) activities and thiobarbituric reactive substances (TBARS) were reduced, resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic dehydrogenase (LDH) activities in plasma. Similar results of these enzymes and biochemical markers in both liver tissues and plasma were seen in ethanol-induced hepatotoxicity of SD rats. In addition, elevated alcohol dehydrogenase (ADH) activity and reduced expression of cytochrome p450 mixed monooxygenase enzyme (CYP2E1) were seen in liver tissues from ethanol-treated rats by LED treatment. These effects of LED were similar to those of Silymarin. In in vitro experiments, LED showed antioxidant activity in a 2,2-diphenyl-1-picrylhydrazyl (DPPH) system and mouse liver mitochondria system induced by NADPH/$Fe^{2+}$ and cumine hydroperoxide (CuOOH). These results indicate that LED protected SD rat hepatotoxicity, induced by $CCl_4$ and ethanol, through its antioxidative activity and might be useful as a material for protection from hepatoxicity in humans.

• Journal of Life Science
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• 제20권5호
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• pp.782-788
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• 2010

The protective effects of a powder mixed with solid-cultured and liquid-cultured Lentinus edodes mycelia (2 : 1, w/w) (designate LED) with different doses of carbon tetrachloride ($CCl_4$) on induced hepatotoxicity in male Sprague-Dawley (SD) rats was investigated. The rats were divided into seven groups (6 rats/group) and the following substances were administered orally to each group: Vehicle (0.2 ml distilled water), Control (0.2 ml distilled water), LED (LED 100, 200, 300 and 400 mg/kg BW in 0.2 ml distilled water), and Silymarin (200 mg/Kg BW in 0.2 ml distilled water). After two weeks of daily administration, all groups except for the Vehiclegroup were subjected to abdominal injection with $CCl_4$ ($CCl_4$ : corn oil, 1 : 1 v/v; 0.5 ml/kg BW). One day later, blood and liver samples were collected to analyze biomarkers. All LED treatments elevated hepatic superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH peroxidase) activities, and reduced thiobarbituric reactive substances (TBARS), tumor necrosis factor-$\alpha$ (TNF-$\alpha$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6), resulting in the reduction of glutamate-oxalate transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactic acid dehydrogenase (LDH) activities in plasma. These results indicate that LED effectively protected SD rat hepatotoxicity induced by $CCl_4$ through its antioxidative activity and reduction of some cytokines. The highest efficacy was found in LED 200 mg/kg BW, showing potential as a useful material for protection from hepatotoxicity in humans.

• Journal of the Korean Society of Fisheries and Ocean Technology
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• 제23권2호
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• pp.61-65
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• 1987

In this study, the characteristics of TRC (tensile restraint crack) critical stress in the gravity type underwater wet welding process and in the in-air welding have been investigated for Y, y and 45$^{\circ}$r grooves using the KR Grade A-3 steel plates and the E4303 covered electrodes. The following results were obtained: (1) In the TRC tests, the initial critical stress of Y groove is higher than those of the 45$^{\circ}$r single bebel grooves in both in-air and underwater weldings, and the cold fracture sensitivity is higher in the underwater welding than in the in-air welding. (2) The hardness of underwater weld metal is the highest in heat affected zone is about Hk 365 in the in-air weld but Hk 670 in the underwater weld which is higher for cooling speed is more rapid, resulting in the lower critical stress by increase of fracture sensitivity. (3) The diffusible hydrogen quantity for 48 hours is about 18cc/100g-weld-metal in the in-air welding but 48cc/100g-weld-metal in the underwater welding. So that, in the case of underwater welding the diffusible hydrogen penetrates about 3 times more than that in the in-air welding.

• Journal of the Korean Society of Fisheries and Ocean Technology
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• 제23권2호
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• pp.15-15
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• 1987

In this study, the characteristics of TRC (tensile restraint crack) critical stress in the gravity type underwater wet welding process and in the in-air welding have been investigated for Y, y and 45°r grooves using the KR Grade A-3 steel plates and the E4303 covered electrodes. The following results were obtained: (1) In the TRC tests, the initial critical stress of Y groove is higher than those of the 45°r single bebel grooves in both in-air and underwater weldings, and the cold fracture sensitivity is higher in the underwater welding than in the in-air welding. (2) The hardness of underwater weld metal is the highest in heat affected zone is about Hk 365 in the in-air weld but Hk 670 in the underwater weld which is higher for cooling speed is more rapid, resulting in the lower critical stress by increase of fracture sensitivity. (3) The diffusible hydrogen quantity for 48 hours is about 18cc/100g-weld-metal in the in-air welding but 48cc/100g-weld-metal in the underwater welding. So that, in the case of underwater welding the diffusible hydrogen penetrates about 3 times more than that in the in-air welding.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 한국표면공학회 2001년도 추계학술발표회 초록집
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• pp.28-28
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• 2001

$TiCl_44,{\;}AICl_3,{\;}H_2,{\;}Ar,{\;}NH_3$ 기체를 사용하여 플라즈마 화학 증착법으로 $(Ti_{1-x}AI_x)N$ 피막을 증착한 후 진공열처리 실험을 통해 열처리 전후에 나타나는 피막의 가계적 특성 변화 및 상변화 양상에 대해 연구하였다. 기판으로는 M2 고속도강과 알루미나(${\alpha}-Al_2O_3$)를 사용하였으며, 열처리 실험은 진공 열처리로를 이용하여 $800$ ~ $1100^{\circ}C$ 에서 진행하였다. M2 고속도강 위에 증착한 $(Ti_{1-x}AI_x)N$ 피막은 모두 (200) 우선 방위를 갖고 있었으며, AI의 함량이 높아짐에 따라 입자의 크기가 미세해져 $(Ti_{0.2}AI_{0.8})N$ 의 경우 수 nm의 업자들로 이루어져 있었다. 열처리 시간을 일정하게 하고, 그 온도를 증가시킬 경우 비교적 낮은 온도 영역($~900^{\circ}C$)에서는 경도 증가를 나타내지만, 열처리가 더욱 진행됨에 따라 다시 경도가 감소하는 양상을 나타내었으며, 열처리 온도를 일정하게 하고 열처리 시간을 변화 시킬 경우에도 초기에 경도가 증가하다가 열처리가 진행됨에 따라 경도가 다시 감소하는 현상을 관찰 하였다. 이때 경도증가 정도는 Al 함량이 높을 수록 뚜렷하고 오래 지속되었으며, $(Ti_{0.2}AI_{0.8})N$ 피막의 경우 열처리 전 $2000HK_{0.01}$에서 열처리 후 $4500HK_{0.01}$로, 매우 큰 경도 증가를 나타내었다. 이와 같은 열처리 전후의 기계적 특성 변화는 준 안정상의 $(Ti_{1-x}AI_{x})N$ 피막에서, 열처리가 진행됨에 따라 미세한 AlN 업자가 석출되면서 나타나는 현상으로, 고분해능 전자현미경(HRTEM) 분석을 통해 경도가 증가한 시편의 경우 석출상의 크기가 5nm 이하로 매우 작고 대체로 기지와 연속적인 계면을 형성하나, 열처리가 진행될수록 석 출상의 크기가 커지고 임계크기 이상에 이르면 연속적인 계면은 거의 발견되지 않고, 대부 분 불연속적이고 확연한 계면을 형성함을 관찰 할 수 있었다. 알루미나(${\alpha}-Al_2O_3$) 기판 위에 증착한 $(Ti_{1-x}AI_{x})N$ 피막은 마찬가지로 (200) 우선 방위를 나타내었으나, 그 입자의 크기가 수십 nm로 고속도강위에 증착한 피막에 비해 상당히 크게 형성되었다. 또한 열처리 후에 AIN의 석출이 진행됨에도 불구하고 경도 증가는 나타나지 않고, 열처리가 진행됨에 따라 경도가 감소하는 양상만을 나타내었다. 결국 $(Ti_{1-x}AI_{x})N$ 피막이 열처리 전후에 보아는 기계적 특성의 변화 양상은 열역학적으로 안정한 Wurzite-AlN의 석출에 따른 것으로 AlN 석출상의 크기에 의존하며, 또한 이러한 영향은 $(Ti_{1-x}AI_{x})N$ 피막에 존재하는 AI의 함량이 높고, 초기에 증착된 막의 업자 크기가 작을 수록 클 것으로 여겨진다.

• Proceedings of the Ginseng society Conference
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• 고려인삼학회 2002년도 학술대회지
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• pp.66-83
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• 2002

Recently, we have provided evidence that ginsenosides, the active components of Panax ginseng, utilize pertussis toxin (PTX)-insensitive $G{\alpha}_{q/11}-phospholipase\;C-{\beta}3(PLC-{\beta}3)$ signal transduction pathway for the enhancement of $Ca^{2+}-activated\;Cl^{-}$ current in the Xenopus oocyte (British J. Pharmacol. 132, 641-647, 2001; JBC 276, 48797-48802, 2001). Other investigators have shown that stimulation of receptors linked to $G{\alpha}-PLC$ pathway inhibits the activity of G proteincoupled inwardly rectifying $K^+$ (GIRK) channel. In the present study, we sought to determine whether ginsenosides influenced the activity of GIRK 1 and GIRK 4 (GIRK 1/4) channels expressed in the Xenopus oocyte, and if so, the underlying signal transduction mechanism. In oocyte injected with GIRK 1/4 channel cRNAs, bath-applied ginsenosides inhibited high potassium (HK) solution-elicited GIRK current $(EC_{50}:4.9{\pm}4.3\;{\mu}g/ml).$ Pretreatment of the oocyte with PTX reduced the HK solution-elicited GIRK current by $49\%,$ but it did not alter the inhibitory ginsenoside effect on GIRK current. Prior intraoocyte injection of cRNA(s) coding $G{\alpha}_q,\;G{\alpha}_{11}\;or\;G{\alpha}_q/G{\alpha}_{11},\;but\;not\;G{\alpha}_{i2}\;or\;G{\alpha}_{oA}$ attenuated the inhibitory ginsenoside effect. Injection of cRNAs coding $G{\beta}_{1{\gamma}2}$ also attenuated the ginsenoside effect. Similarly, injection of the cRNAs coding regulators of G protein signaling 1, 2 and 4 (RGS1, RGS2 and RGS4), which interact with $G{\alpha}_i\;and/or\;G{\alpha}_{q/11}$ and stimulates the hydrolysis of GTP to GDP in active GTP-bound $G{\alpha}$ subunit, resulted in a significant reduction of ginsenoside effect on GIRK current. Preincubation of GIRK channel-expressing oocyte in PLC inhibitor (U73122) or protein kinase C (PKC) inhibitor (staurosporine or chelerythrine) blocked the inhibitory ginsenoside effect on GIRK current. On the other hand, intraoocyte injection of BAPTA, a free $Ca^{2+}$ chelator, had no significant effect on the ginsenoside action. Taken together, these results suggest that ginsenosides inhibit the activity of GIRK 1/4 channel expressed in the Xenopus oocyte through a PTX-insensitive and $G{\alpha}_{q/11}$-,PLC-and PKC-mediated signal transduction pathway.

• Microbiology and Biotechnology Letters
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• 제23권2호
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• pp.138-144
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• 1995

The cDNA, encoding human lysozyme (HLY) which was isolated from a human placenta cDNA library, has been well characterized (Yoshimura et al., 1988). Based on the communication, we have prepared an artificial HLY gene from chemically synthesized 38-oligomer with high codon usage in Saccharomyces cerevisiae. For directing the synthesis and secretion of HLY in S. cerevisiae, an expression vector, pHKl was constructed by inserting the HLY gene, containing a synthetic HLY secretion signal sequence, between the yeast GAP promoter and PH05 terminator. From a lysoplate assay, we have confirmed an yeast transformant harboring a pHK1 which makes a clearing zone on the overlayed Micrococcus luteus. This result means a chemically synthesized HLY gene which was normally expressed and secreted in yeast.

• Animal cells and systems
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• 제8권4호
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• pp.329-333
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• 2004

Japanese flounder (Paralichthys olivaceus) head kidney (HK) leukocytes were incubated with $10^3$ to $10^{-3}$ ng levamisole/ml for 4, 24 or 48 h and then assayed for their natural cytotoxic activity against xenogeneic tumor cells. This activity was slightly increased after 24 h of incubation. In a second experiment, fish were fed 0, 75, 150 or 300 mg levamisole/kg diet for 10 consecutive days. The fish were then fed a commercial non-supplemented diet and sampled 0, 1, 2, 3, 4 or 6 weeks post-administration of levamisole. The cytotoxic activity was found to be increased with increasing levamisole dose and remained greatly enhanced until the end of the experiment. In conclusion, levamisole enhanced flounder natural cytotoxic cell activity both in vitro and in vivo and had a great lasting action when administered by feeding.