• The Journal of Korean Medicine
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• v.23 no.3
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• pp.74-84
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• 2002

목적 : 본 실험에서는 gerbil을 이용한 전뇌허혈 동물모델에서 뇌허혈손상 직후 지연성 뇌손상에 대한 대황의 방어효과와 Apoptosis 과정중의 Bax와 Bcl-2 단백질에 대한 조절작용을 관찰하고, TUNEL 염색법을 통하여 대황이 gerbil hippocampus CAl영역의 pyramidal neuron의 세포사에 미치는 영향과 PCl2세포를 이용한 세포배양 모델에서의 대황의 신경방어 효과를 관찰하였다. 방법 : Mongolian gerbil의 총경동맥을 5분간 폐색하여 가역성 전뇌허혈을 유발시킨 후 대황의 전탕액을 하루에 한번 경구 투여하였다. 대황의 신경 보호 효과는 수술 7일 후에 cresyl violet으로 염색하여, 살아있는 신경 세포의 수를 세어 측정하였다. 또, 수술 3일 후에는 면역조직화학적 방범을 통하여 Bax. Bcl-2단백질의 발현과 대황의 신경보호 효과와의 관련성을 알아보았다. 결과： 가역적 전뇌허혈이 일어난 동물군의 경우 hippocampus의 CAl 영역에서 살아있는 신경세포의 수는 $51.0{\pm}2.5개{\;}/mm$에 불과하였으나, 그에 비해 수술 후 7일간 대황을 투여한 동물군은 $106.2{\pm}2.5개{\;}/mm$로 살아 있는 신경세포수가 크게 증가하였다. Apoptosis를 촉진하는 단백질인 Bax의 발현은 3일간 대황을 투여한 동물군의 경우 hippocampus의 CAl 영역에서 현저하게 저해되었고, Apoptosis를 억제하는 Bcl-2 단백질의 발현은 변화가 없었다. TUNEL assay를 통하여 살펴본 결과 대황 투여군의 apoptotic 신경세포사가 감소하였으며 이는 Bax protein의 발현과 유사한 양상을 나타내었다. 결론：대황이 Bax 단백질의 발현을 억제하여 상대적으로 Bax/Bcl-2 자연적 세포사를 억제하여 Mogolian gerbil의 가역성 전뇌허혈 모델에서 신경보호효과를 나타내는 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.625-631
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• 2012

In order to investigate whether SKI-II could reverse drug resistance and its possible mechanisms, we treated SGC7901/DDP cells with SKI-II or SKI-II in combination with DDP. Then cell growth, apoptosis, micromorphological changes, and expression of SphK1, P-gp, NF-${\kappa}B$, Bcl-2 and Bax were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistry and Western blot assay respectively. SGC7901/DDP cells were insensitive to cisplatin 2.5mg/L, but when pretreated with SKI-II, their proliferation was inhibited by cisplatin 2.5mg/L significantly, the inhibition rate increasing with time and dose. The apoptosis rate was also significantly elevated. Expression of SphK1 and P-gp was decreased significantly, Pearson correlation analysis showing significant correlation between the two (r=0.595, P<0.01). Expression of NF-${\kappa}B$ and Bcl-2 was decreased significantly,while that of Bax was increased, compared to the control group. There were significant correlations between SphK1 and NF-${\kappa}B$(r=0.723, P<0.01), NF-${\kappa}B$ and Bcl-2(r=0.768, P<0.01). All these data indicated that SKI-II could reverse drug resistance of SGC7901/DDP to cisplatin by down-regulating expression of P-gp and up-regulating apoptosis through down-regulation of SphK1. The increased apoptotic sensitivity of SGC7901/DDP to cisplatin was due to the decreasing proportion of Bcl-2/Bax via down-regulating NF-${\kappa}B$.

• Molecules and Cells
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• v.38 no.3
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• pp.279-284
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• 2015

Obatoclax, a pan-Bcl2 inhibitor, shows antitumor activities in various solid malignancies. Bcl2-deficient mice have shown the importance of Bcl2 in osteoclasts, as the bone mass of the mice was increased by the induced apoptosis of osteoclasts. Despite the importance of Bcl2, the effects of obatoclax on the proliferation and differentiation of osteoclast precursors have not been studied extensively. Here, we describe the anti-proliferative effects of obatoclax on osteoclast precursors and its negative role on fusion of the cells. Stimulation with low doses of obatoclax significantly suppressed the proliferation of osteoclast precursors in a dose-dependent manner while the apoptosis was markedly increased. Its stimulation was sufficient to block the activation of ERK MAP kinase by RANKL. The same was true when PD98059, an ERK inhibitor, was administered to osteoclast precursors. The activation of JNK1/2 and p38 MAP kinase, necessary for osteoclast differentiation, by RANKL was not affected by obatoclax. Interestingly, whereas the number of TRAP-positive mononuclear cells was increased by both obatoclax and PD98059, fused, multinucleated cells larger than $100{\pm}m$ in diameter containing more than 20 nuclei were completely reduced. Consistently, obatoclax failed to regulate the expression of osteoclast marker genes, including c-Fos, TRAP, RANK and CtsK. Instead, the expression of DC-STAMP and Atp6v0d2, genes that regulate osteoclast fusion, by RANKL was significantly abrogated by both obatoclax and PD98059. Taken together, these results suggest that obatoclax down-regulates the proliferation and fusion of osteoclast precursors through the inhibition of the ERK1/2 MAP kinase pathway.

• Journal of Korean Society of Forest Science
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• v.104 no.3
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• pp.383-389
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• 2015

The purpose of this study was to investigate the anti-apoptosis-related protein expression in skeletal muscle of rats with different amount of mountain ginseng (MG) added high-fat diet fed. Twenty-four Sprague Dawley male rats were divided into the high-fat diet control group (CON), 0.5% of MG added diet group (MG1), and 1.0% of MG added diet group (MG2) with eight rats each. The P53, anti-apoptotic protein, was significantly lower in MG2 than CON and MG1. The bcl-2 and bcl-xl, however, were not significantly different from MG1 but from CON. The caspase-9 and -3, were significantly lower in MG groups than CON. In addition, it was dramatically lower in MG2. These results suggested that MG addition to the high-fat diet suppressed p53 protein expression and enhanced anti-apoptototic protein expression. MG may be a positive effects on health as a medicinal plant.

• Biomolecules & Therapeutics
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• v.26 no.5
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• pp.464-473
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• 2018

Cripto is a small glycosylphosphatidylinositol-anchored signaling protein that can detach from the anchored membrane and stimulate proliferation, migration, differentiation, vascularization, and angiogenesis. In the present study, we demonstrated that Cripto positively affected proliferation and survival of mesenchymal stem cells (MSCs) without affecting multipotency. Cripto also increased expression of phosphorylated janus kinase 2 (p-JAK2), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), 78 kDa glucose-regulated protein (GRP78), c-Myc, and cyclin D1. Notably, treatment with an anti-GRP78 antibody blocked these effects. In addition, pretreatment with STAT3 short interfering RNA (siRNA) inhibited the increase in p-JAK2, c-Myc, cyclin D1, and BCL3 levels caused by Cripto and attenuated the pro-survival action of Cripto on MSCs. We also found that incubation with Cripto protected MSCs from apoptosis caused by hypoxia or $H_2O_2$ exposure, and the level of caspase-3 decreased by the Cripto-induced expression of B-cell lymphoma 3-encoded protein (BCL3). These effects were sensitive to down-regulation of BCL3 expression by BCL3 siRNA. Finally, we showed that Cripto enhanced expression levels of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). In summary, our results demonstrated that Cripto activated a novel biochemical cascade that potentiated MSC proliferation and survival. This cascade relied on phosphorylation of JAK2 and STAT3 and was regulated by GRP78. Our findings may facilitate clinical applications of MSCs, as these cells may benefit from positive effects of Cripto on their survival and biological properties.

• Clinical and Experimental Pediatrics
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• v.62 no.3
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• pp.95-101
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• 2019

Purpose: Increased apoptosis was recently found in the hypertrophied left ventricle of spontaneously hypertensive rats (SHRs). Although the available evidence suggests that apoptosis can be induced in cardiac cells by various insults including pressure overload, cardiac apoptosis appears to result from an exaggerated local production of angiotensin in adult SHRs. Altered expressions of Bcl associated X (Bax), Bcl-2, chemokine receptor (CCR)-2, monocyte chemoattractant protein (MCP)-1, transforming growth factor $(TGF)-{\beta}1$, phosphorylated extracellular signal-regulated kinases (PERK), and connexin 43 proteins, and kallikrein mRNA were investigated to explore the effects of losartan on the SHR model. Methods: Twelve-week-old male rats were grouped as follows: control (C), SHR (hypertension: H), and losartan (L; SHRs were treated with losartan [10 mg/kg/day] for 5 weeks). Western blot and reverse transcription polymerase chain reaction assays were performed. Results: Expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, PERK, and connexin 43 proteins, and kallikrein mRNA was significantly increased in the H group compared to that in the C group at weeks 3 and 5. Expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, and connexin 43 proteins and kallikrein mRNA was significantly decreased after losartan treatment at week 5. PERK protein expression was significantly decreased after losartan treatment at weeks 3 and 5. Bcl-2 protein expression was significantly decreased in the H group compared to that in the C group at weeks 3 and 5. Conclusion: Losartan treatment reduced expression of Bax, CCR-2, MCP-1, $TGF-{\beta}1$, PERK, and connexin 43 proteins, and kallikrein mRNA in SHRs, along with decreased inflammation and apoptosis.

• Proceedings of the Korean Vacuum Society Conference
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• 2012.02a
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• pp.114-114
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• 2012

Metal-oxide-semiconductor field-effect transistors (MOSFETs)의 critical dimension (CD)가 sub 45 nm로 줄어듬에 따라 기존에 gate dielectric으로 사용하고 있는 SiO2에서 발생되는 high gate leakage current 때문에 새로운 high dielectric constant (k) 물질들이 연구되기 시작하였다. 여러 가지 high-k 물질 중에서, aluminum-oxide (Al2O3)는 높은 dielectric constant (~10)와 전자 터널링 barrier height (~2eV) 등을 가지기 때문에 많은 연구가 되고 있다. 그러나 Al2O3를 anisotropic한 patterning을 하기 위해 주로 사용되고 있는 halogen-based 플라즈마 식각 과정에서 나타나는 Al2O3와 하부 layer간의 낮은 식각 selectivity 뿐만 아니라 표면에 발생되는 defect, stoichiometry modification, roughness 변화 등의 많은 문제점들로 인하여 device performance가 감소하기 때문에 이를 해결하기 위한 많은 연구들이 진행중이다. 따라서 본 연구에서는 실리콘 기판위의 atomic layer deposition (ALD)로 증착된 Al2O3를 BCl3/Ar 중성빔을 이용하여 원자층 식각한 후 식각 특성을 분석해 보았다. Al2O3 표면을 BCl3로 absorption시킨 후 Ar 중성빔으로 desorption 시키는 과정에서 volatile한 aluminum-chlorides와 boron oxychloride가 형성되어 layer by layer로 제거됨을 관찰 할 수 있었다.

• Journal of Chest Surgery
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• v.34 no.6
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• pp.447-453
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• 2001

Background: Although pulmonary resection is the standard approach for the management of pulmonary metastases from soft tissue sarcoma, most of them are unresectable and chemotherapy remains the only option. The effectiveness of the cytotoxic drugs may be limited by the toxicities that occur before the therapeutic dose is reached. The regional administration of doxorubicin using pulmonary arterial perfusion in a rodent model can produce 10 to 25 times higher concentrations in the lung than systemic administration with minimal systemic toxicities. However, it is unclear whether a high concentration of doxorubicin has beneficial effects for killing cancer cells. Material and Method: We studied this to evaluate the dose-dependent cytotoxic and apoptotic effects of doxorubicin on methylcholanthrene-induced rat fibrosarcoma(MCA) cells. This study examined the cytotoxicity and apoptosis-related gene expressions(Fas, FasL, Bax, caspase 1, caspase 2, caspase 8, Bcl-2, Bcl-xL, Bcl-xS) in MCA cells after 24 hours exposure to various concentrations of doxorubicin such as 1, 5, 10, 50, and 100 $\mu$M. Result: Dose-dependent cytotoxicity was observed after 24 hours exposure to doxorubicin. However, peak apoptosis after 24 hours exposure was observed at 5 $\mu$M of doxorubicin. Above 5 $\mu$M, apoptotic activity was decreased with dose-increment. All mRNA levels of apoptosis-related genes after 24 hours exposure were up-regulated above the control level at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment except caspase 8, which showed higher levels than the control level at 5 $\mu$M. Apoptosis-related protein levels were highest at 1 $\mu$M of doxorubicin and then decreased by doxorubicin dose-increment. However, Bax and Bcl-xL proteins steadily showed higher levels than the control throughout the different concentrations of doxorubicin. Conclusion: These results suggest that apoptosis is the main cytotoxic mechanism in low concentrations of doxorubicin in MCA cells and apoptosis-related genes, such as Bax, caspase 8, and Bcl-xL, are involved. At high concentrations, doxorubicin still can kill MCA cells, even when apoptosis is inhibited, and have its propriety for achieving much cytotoxicity against MCA cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.1
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• pp.8-15
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• 2008

Saussurea lappa (SL) has been used to reduce abdominal pain and tenesmus in traditional oriental medicine. SL and major compounds of SL, sesquiterpene lactones, have been suggested to possess various biological effects, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral and cardiotonic activities. Recently, it has been reported that ethanol extracts from roots of SL have antiproliferative effects on gastric cancer cells. To explore the possibility that SL has chemopreventive effects on prostate cancer, we examined whether the hexane extract of SL (HESL) inhibits the growth of LNCaP human prostate cancer cells. Cells were incubated with various concentrations ($0{\sim}4$ mg/L) of HESL in DMEM/F12 containing 5% charcoal stripped fetal bovine serum. HESL substantially decreased viable cell numbers and induced apoptosis of LNCaP cells in dose-dependent manners. HESL increased the levels of cleaved caspase-8, -9, -7 and -3, and poly (ADP-ribose) polymerase. HESL increased the levels of the pro-apoptotic Bak and truncated-Bid proteins whereas it had no effect on the anti-apoptotic Bcl-2, Bcl-xL, or Mcl-1. The present results indicate that HESL inhibits the growth of human prostate cancer cells by inducing apoptosis, which involves the activation of the caspase cascades.

• Korean Journal of Veterinary Research
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• v.45 no.1
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• pp.17-23
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• 2005

In the present study, we expected the anti-tumor effect by combined treatment of arsenic trioxide and interferon (IFN)-${\alpha}$ on murine Lewis lung carcinoma (LL2) cells through in vivo study. As a experimental model, LL2 cells ($1{\times}10^{6}$/mouse) were injected subcutaneously into the back region of mice. When the tumor volume reached $100mm^3$, mice were treated with 1 mg/kg arsenic trioxide, 50000 IU IFN-${\alpha}$, or arsenic trioxide and IFN-${\alpha}$. The development of tumor cells was significantly inhibited by combined treatment with arsenic trioxide and IFN-${\alpha}$. In arsenic trioxide and IFN-${\alpha}$ treated group, apoptotic index was reached a peak valve at 48 hr after the treatment and it was restored to approximately the control level at 8 days. Also, positive signals of Bax and Bad were increased at 48 to 96 hr and decreased at 8 day. Whereas, positive cells of Bcl-2 were steadily decreased at 12 to 48 hr and restored to the background level at 8 days. Our data showed that immunoreactivity of Bcl-2 was decreased at 12 to 48 hr, while positive signals of Bax and Bad were increased in accordance with apoptotic index at these times. In conclusion, our results suggest that the combined treatment with arsenic trioxide and IFN-${\alpha}$ significantly inhibited the growth of LL2 tumor cells and induced apoptosis through the up and down-regulation of Bcl-2 gene family.