• Archives of Pharmacal Research
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• 제27권1호
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• pp.68-76
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• 2004

Mistletoe lectin has been reported to induce apoptosis in different cancer cell lines in vitro and to show antitumor activity against a variety of tumors in animal models. We previously demonstrated the Korean mistletoe lectin (Viscum album var. coloratum, VCA)-induced apoptosis by down-regulation of Bcl-2 and telomerase activity and by up-regulation of Bax through p53- and p21-independent pathway in hepatoma cells. In the present study, we observed the induction of apoptotic cell death through activation of caspase-3 and the inhibition of telomerase activity through transcriptional down-regulation of hTERT in the VCA-treated A253 cells. We also observed the inhibition of telomerase activity and induction of apoptosis resulted from dephosphorylation of Akt in the survival signaling pathways. In addition, combining VCA with the inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) upstream of Akt, wortmannin and LY294002 showed an additive inhibitory effect of telomerase activity. In contrast, the inhibitor of protein phosphatase 2A (PP2A), okadaic acid inhibited VCA-induced dephosphorylation of Akt and inhibition of telomerase activity. Taken together, VCA induces apoptotic cell death through Akt signaling pathway in correlated with the inhibition of telomerase activity and the activation of caspase-3. From these results, together with our previous studies, we suggest that VCA triggers molecular changes that resulting in the inhibition of cell growth and the induction of apoptotic cell death of cancer cells, which suggest that VCA may be useful as chemotherapeutic agent for cancer cells.

• 한국축산식품학회지
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• 제18권2호
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• pp.157-163
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• 1998

This study was carried out to examine that pepsin-hydrolyzed bovine lactoferrin has applicabilities which are market milk and dairy products. The stability of pepsin-hydrolyzed bovine apo-lactoferrin and the change of its antibacterial character has been studied under various method for pasteurization (LTLT; 65$^{\circ}C$ / 30min., HTST ; 75$^{\circ}C$ / 15sec., UHT ; 135$^{\circ}C$ / 3sec.) and pH Values (pH 2.0, pH 4.0, pH 6.8). The ehated samples were assayed for minimal bacteriocidal concentrations (MBCs) and bacteriocidal effect against E. coli. The results obtained were summarized as follows: After fractionation of pepsin-hydrolyzed bovine lactofeerin by gel filtration. several peptide fractions were found that had strong antibacterial activity. SDS-PAGE showed that the one of these fractions with strong antibacterial activity, which had a molecular mass a range of 30∼33KDa. The MBCs for pepsin-hydrolyzed bovine lactoferrin fraction No. 2 against E. coli required to cause complete inhibition of growth varied within the range of 200∼400 $\mu\textrm{g}$/ml, depending on heat treatments and pH conditions. The peptide fraction No. 2 showed strong bacteriocidal activity against E. coli at LTLT and HTST treatments under acidic pH conditions. and was reduced activity at UHT treatment under pH 6.8 condition.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.83-91
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• 1999

Angiotensin II (ANG II) has a biphasic effect on $Na^+$ transport in proximal tubule: low doses of ANG II increase the $Na^+$ transport, whereas high doses of ANG II inhibit it. However, the mechanisms of high dose ANG II-induced inhibition on $Na^+$ uptake are poorly understood. Thus the aim of the present study was to investigate signal transduction pathways involved in the ANG II-induced inhibition of $Na^+$ uptake in the primary cultured rabbit renal proximal tubule cells (PTCs) in hormonally defined serum-free medium. ANG II $(10^{-9}\;M)-induced$ inhibition of $Na^+$ uptake was blocked by losartan $(10^{-8}\;M,\;AT_1\;antagonist),$ but not by PD123319 $(10^{-8}\;M,\;AT_2\;antagonist)$ (P<0.05). ANG II-induced inhibition of $Na^+$ uptake was also completely abolished by neomycin $(10^{-4}\;M,$ PLC inhibitor), W-7 $(10^{-4}\;M,$ calmodulin antagonist), and $AACOCF_3\;(10^{-6}\;M,\;PLA_2\;inhibitor)$ (P<0.05). ANG II significantly increased $[^3H]arachidonic$ acid (AA) release compared to control. The ANG II-induced $[^3H]AA$ release was blocked by losartan, $AACOCF_3,$ neomycin, and W-7, but not by PD123319. ANG II-induced $[^3H]AA$ release in the presence of extracellular $Ca^{2+}$ was greater than in $Ca^{2+}-free$ medium, and it was partially blocked by TMB-8 $(10^{-4}\;M,$ intracelluar $Ca^{2+}$ mobilization blocker). However, in the absence of extracellular $Ca^{2+},$ it was completely blocked by TMB-8. In addition, econazole $(10^{-6}\;M,$ cytochrome P-450 monooxygenase inhibitor) and indomethacin $(10^{-6}\;M,$ cyclooxygenase inhibitor) blocked ANG II-induced inhibition of $Na^+$ uptake, but NGDA $(10^{-6}\;M,$ lipoxygenase inhibitor) did not affect it. In conclusion, $PLA_2-mediated$ AA release is involved in ANG II-induced inhibition of $Na^+$ uptake and is modulated by $[Ca^{2+}]_i$ in the PTCs.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2002년도 생물공학의 동향 (X)
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• pp.431-434
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• 2002

단일균이나 활성슬러지를 이용하여 폐수를 처리하고자 할 때 폐수의 pH 가 단일균이나 활성 슬러지의 최적 pH 에 적합하지 아니한 경우에는 미생물을 고정화하여 희망하는 pH에서 최대의 분해활성을 나타내도록 최적 pH를 어느정도 변화시킬 수 있으며, 기존의 활성슬러지법 보다는 활성 슬러지를 고정화하여 처리하는 것이 높은 부하에서도 제거 효율이 높기 때문에 반응조의 콤펙트화가 가능할 것으로 사료된다.

• 미생물학회지
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• 제37권2호
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• pp.151-157
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• 2001

위염 및 위궤양, 심이지장궤양, 위암의 주요한 발병 원인균으로 알려져 있는 Helicobacter pylori의 생육을 특이적으로 억제하는 유산균을 선발하기 위해서, 45종의 유산균에 대하여 paper disk법을 이용한 항균 효과, Caco-2세포에 대한 정착능, urease activity법을 이용한 H. pylori 억제능 등을 파악하고, 유산균 배양액과 H. pylori의 동시배양에 따른 요소 분해효소의 활성 변화와 우유 발효능 등을 실험하였다. H. pylori의 생육을 억제하는 물질의 생성 유무를 확인하기 위하여 paper disk법으로 유산균 배양액에 의한 H. pylori의 생육 억제환을 측정한 결과, 28종의 유산균에서 생육 억제환이 형성되었다. 대부분이 유산 생성에 의한 낮은 pH 때문인 것으로 판단되지만, 일부 균종에서는 항균성 물질에 의한 억제환이 형성되었다. 다른 유산균에 비해서 생육 억제환이 가장 큰 Lactobacillus gasseri MK-03 균주가 H. pylori에 대한 항균 활성이 가장 우수한 것으로 나타났다. 항균 활성을 나타낸 28종의 유산균을 대항으로 Caco-2 세포에 대한 정착능을 실험한 결과, 18종의 유산균에서 정착능이 확인되었으며, Bifidobacterium longum MK-26 균주가 가장 우수한 것으로 나타났다. 특히 반응 2시간 전에 미리 Caco-2 세포에 정착시켰을 때, H. pylori의 정착율은 0.105%에서 0.004%로 감소되었다. 한편 요소 분해효소 활성을 저해하여 H. pylori를 억제하는 유산균을 선발하기 위해서 항균활성이 인정되는 28종의 유산균을 대상으로 실험한 결과, 21종의 유산균에서 요소 분해효소 활성의 저해 효과가 나타났으며, 이중에서 Lb. acidophilus MK-07 균주가 가장 우수한 것으로 판명되었다. 따라서 Lb. gasseri MK-03 균주는 항균 활성에서, Lb. acidophilus MK-07 균주는 요소 분해효소의 활성 억제에 의해서, Bif. longum MK-26 균주는 정착능 저해에 있어서 각각 우수한 H. pylori 생육 억제능을 나타냈다. 한편 최종적으로 선발된 3종의 유산균과 대조균주로서 13종의 유산균에 대해서는 우유 배양실험을 실시한 결과, 3종의 선발균주 모두가 발효유 제품에의 응용 적합성을 나타냈다.

• BMB Reports
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• 제29권3호
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• pp.210-214
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• 1996

The pH dependence of the kinetic parameters of mutant O-acetylserine sulfhydrylase (OASS) from Salmonella typhimurium LT-2 has been determined in order to obtain information on the chemical mechanism. The initial velocity pattern obtained by varying the concentrations of OAS at several fixed concentrations of TNB, shows an intersection on the left of the ordinate at pH 7.0, indicating that the kinetic mechanism is a sequential mechanism in which substrate inhibition by OAS is observed while the wild type enzyme showed a ping pong mechanism. The values of $V/E_t$, $V/K_{OAS}E_{t}$ and $V/K_{TNB}E_{t}$ decreased by about 68%, 14% and 16% as compared with the wild type enzyme. The $V/K_{OAS}E_{t}$ is a pK of 6.5 on the acid side of the pH profile, and the $V/K_{TNB}$ is pH independent. As compared with the wild type enzyme, the pKs in the V/K profiles are shifted, reflecting that binding of the cofactor in free E:OAS is less asymmetric.

• Advances in nano research
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• 제12권6호
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• pp.639-652
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• 2022

The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.

• 대한화장품학회지
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• 제30권1호
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• pp.29-32
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• 2004

내형질 세망 조직에서 N-글리코실레이션 과정의 초기 단계를 차단하면 멜라닌 생 합성의 주 효소인 티로시나제의 활성이 저해된다. 본 연구에서는 in vitro 환경에서 N-글리코실레이션 저해제의 활성을 증가시키고자 전달체로 pH 감응성을 갖는 나노크기의 지질구조체를 제조하고 이를 평가하였다. 이 pH 감응성 지질구조체 Melexsome은 일반적인 지질성분인 포스포리피드와 콜레스테롤 기반의 지질안정 성분으로 구성되며, 통상적인 리포좀 제조법에 따라 제조되었다. 글리코실레이션 저해 성분물질을 포집시킨 Melel[some의 효과는 EndoH ＆ PNGaseF 분해와 western blotting 방법에 의해 평가하였고, 멜라닌 합성량 또한 측정 되었다. 이 결과, pH 감응성을 갖도록 제조된 Melexsome이 N-글리코실레이션 저해제의 효능을 효과적으로 증진시킴을 알 수 있었다. 또한, 공초점 주사 현미경에 의한 세포관찰 결과에 따르면 Melexsome은 여타의 전달체에 비하여 세포질 내에 보다 효과적으로 전달되는 것으로 보여지며, 따라서 이같은 양친성 지실성분 기반의 pH 감응성 나노 전달체는 N-글리코실레이션 저해제의 전달 시스템으로서 미백 화장료 제품이 가져야 하는 침착된 색소에 의해 어두워진 피부톤의 개선 효과를 극대화 시키는데 적합하다고 여겨진다.

• 상하수도학회지
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• 제13권4호
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• pp.35-44
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• 1999

In this study, it was attempted to remove nitrate and carbon in a single-stage reactor using acetate as substrate. Hybrid type upflow sludge baffled filter reactor was adopted using anaerobic sludge. Sludge bed in the bottom of reactor was intended to remove carbon and nitrate by denitrification and methanogenesis. And floating media in the upper part of reactor were intended to remove remaining carbon which was not removed due to the inhibition of nitrogen oxide on methane producing bacteria. The reactor removed over 96% of COD and most of nitrate with volumetric loading rate of $4.0kgCOD/m^3{\cdot}day$, hydraulic retention time of 24hr, 4,000mgCOD/L, and $266mgNO_3-N/L$. Nitrate in anaerobic sludge was converted to nitrogen gas(denitrification) or ammonia (ammonification) according to pH of influent, COD removal efficiency was easily affected by the change of volumetric loading rates and nitrate concentration. And when influent pH was about 4.7, most nitrate changed to ammonia while when influent pH was about 6.8~7.0, most nitrate denitrified independent of $COD/NO_3-N$ ratio. Most granules were gray and a few were black. In gray-colored granule, black inner side was covered with gray substance and SEM illustrated Methanoccoci type microorganisms which were compact spherical shape. Anaerobic filter removed residual COD effectively which was left in sludge bed due to the inhibition of nitrogen oxide.

• 대한본초학회지
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• 제25권2호
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• pp.65-70
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• 2010

Objectives : Biological activities of marine resources have been rarely evaluated compared with other herbal medicines. In the present study, we aimed to evaluate antimicrobial activities of aqueous and ethanolic extracts of five marine resources(Porphyra tenera, Laminariae Thallus, Sargassum, Ostreae Concha, Maliotidis Concha) against Propionibacterium acnes. Methods : Aqueous axtracts of five marine resources were prepared by decocting in tenfold tap water for 3 h. Etanolic extracts were obtained by extracting five marine resources with tenfold ethanol for 72 h at room temperature. The zone of growth inhibition and minimum inhibitory concentration (MIC) were determined against P. acnes after incubation for 48 h under anaerobic condition. Results : Ethanolic extracts of Porphyra tenera exhibited potent antimicrobial effects(MIC $62.5\;{\mu}g/m{\ell}$ against KCTC3320, MIC $31.25\;{\mu}g/m{\ell}$ against KCTC5527). However, all aqueous extracts tested had no effects on the growth inhibition of P. acnes. In addition, four ethanolic extracts except Porphyra tenera showed little inhibitory effect. Conclusions : These results indicate that ethanolic extracts of Porphyra tenera has antimicrobial activities against P. acnes and also warrant further development of Porphyra tenera extracts as a natural anti-acne agent.