• 한국미생물·생명공학회지
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• 제40권2호
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• pp.83-91
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• 2012

본 총설은 N-acyl-homoserine lactone (AHL)에 기반한 quorum sensing(QS)을 비롯한 다양한 QS 시스템 및 생물막 형성과의 관련성에 대한 연구 동향을 정리하였다. 또한 anti-QS으로서 quorum quenching 전략을 이용한 생물막 억제 연구 동향에 대해 중점적으로 서술하였다. 세균의 독특한 신호전달 체계인 QS는 AHL과 같은 특정한 신호분자의 농도에 의해 세균의 집단적 행동 양식이 결정되는 세포밀도-의존성 유전자 발현 조절 메커니즘이다. QS 시스템은 미생물의 부착 및 생물막 형성에 있어 중요한 역할을 한다. AI-1이나 AI-2에 의한 QS는 생물막 형성 과정에 필요한 세포외 다당류, 단백질, 세포 외 DNA 등 주요한 구성 성분 등의 생산뿐만 아니라, 세균의 운동성 조절, 부착, 생물막 해체 과정까지도 조절하는 기능을 한다. 일부 세균의 경우 QS시스템 이외에도 second messenger로 알려진 c-di-GMP에 의한 signaling이 QS와 서로 연결되어 생물막 형성이나 병독성과 같은 타깃들을 함께 조절한다. 생물막은 병원성 세균에 의한 감염 시 여러 가지 병독성 가운데 가장 중요한 요소 중 하나이기 때문에, 생물막 형성을 조절하는 QS를 차단하기 위한 다양한 anti-quorum sensing 전략이 연구되고 있다. Anti-QS 접근 방식은 의학적 이용뿐만 아니라 물에 노출되어있는 MBR을 비롯한 많은 산업적 장치 등에서 생물막 형성으로 인한 손상 및 오염을 방지하기 위해 쓰일 수 있다. Anti-QS 전략 중 신호분자인 AHL을 무력화 시키는 quorum quenching 효소(AHL-lactonase, AHL-acylase, oxidoreductas)를 이용하여 생물막 형성을 억제할 수 있으며, 막을 이용한 수처리 공정에서 막에 발생하는 biofouling을 완화시킬 수 있는 새로운 anti-fouling 처리 기술로서 이러한 QQ 효소의적용 가능성을 보여 주고 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제15권1호
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• pp.1-7
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• 2011

Many anticancer agents as well as ionizing radiation have been shown to induce autophagy which is originally described as a protein recycling process and recently reported to play a crucial role in various disorders. In HCT116 human colon cancer cells, we found that curcumin, a polyphenolic phytochemical extracted from the plant Curcuma longa, markedly induced the conversion of microtubule-associated protein 1 light chain 3 (LC3)-I to LC3-II and degradation of sequestome-1 (SQSTM1) which is a marker of autophagosome degradation. Moreover, we found that curcumin caused GFP-LC3 formation puncta, a marker of autophagosome, and decrease of GFP-LC3 and SQSTM1 protein level in GFP-LC3 expressing HCT116 cells. It was further confirmed that treatment of cells with hydrogen peroxide induced increase of LC3 conversion and decrease of GFP-LC3 and SQSTM1 levels, but these changes by curcumin were almost completely blocked in the presence of antioxidant, N-acetylcystein (NAC), indicating that curcumin leads to reactive oxygen species (ROS) production, which results in autophagosome development and autolysosomal degradation. In parallel with NAC, SQSTM1 degradation was also diminished by bafilomycin A, a potent inhibitor of autophagosome-lysosome fusion, and cell viability assay was further confirmed that cucurmin-induced cell death was partially blocked by bafilomycin A as well as NAC. We also observed that NAC abolished curcumin-induced activation of extracelluar signal-regulated kinases (ERK) 112 and p38 mitogen-activated protein kinases (MAPK), but not Jun N-terminal kinase (JNK). However, the activation of ERK1/2 and p38 MAPK seemed to have no effect on the curcumin-induced autophagy, since both the conversion of LC3 protein and SQSTM1 degradation by curcumin was not changed in the presence of NAC. Taken together, our data suggest that curcumin induced ROS production, which resulted in autophagic activation and concomitant cell death in HCT116 human colon cancer cell. However, ROS-dependent activation of ERK1/2 and p38 MAPK, but not JNK, might not be involved in the curcumin-induced autophagy.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.281-285
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• 2013

Purpose: To probe the role of FasL in cell apoptosis in oral squamous cell carcinomas (OSCCs). Methods: The expression of Fas/FasL was assessed in 10 cases of normal oral epithelium, 38 cases of OSCC and tumor infiltrating lymphocytes (TIL), and 11 cases of metastatic lymph nodes by immunohistochemistry. Apoptosis of tumor cells and TIL was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). FasL-induction of T cell apoptosis was tested by co-culture assay in vitro with SCC-9 and Jurkat T cells. Results: The 10 cases of normal oral epithelium all demonstrated extensive expression of Fas, the positive rate being largely down-regulated in OSCC (21/38) (P<0.05) compared to the normal (10/10). At the same time, the positive rate of FasL significantly increased in OSCC (P<0.05) especially those with lymph node metastasis (P<0.05). The positive rates of Fas in well and middle differentiated OSCC were higher than those in poor differentiated OSCC (P<0.05). The AI of tumor cells in Fas-positive OSCC was remarkably higher than that in Fas-negative OSCC (P<0.01), with a positive correlation between Fas expression and cell differentiation as well as apoptosis (r=0.68, P<0.01). The AI of tumor cells in FasL positive OSCC was remarkably lower than that in control while the AI of TIL was higher than in FasL negative OSCC (P<0.05). The AI of tumor cells reversely correlated with that of TIL (r = -0. 72, P<0.05). It was found that SCC-9 cells expressing functional FasL could induce apoptosis of Jurkat cells as demonstrated by co-culture assays. As a conclusion, it is evident that OSCC cells expressing FasL can induce apoptosis in Fas-expressing T cells. Conclusions: In progression of OSCC, expression of the Fas/FasL changes significantly. The results suggest that FasL is a mediator of immune privilege in OSCC and may serve as an marker for predicting malignant change in oral tissues.

• 대한전자공학회논문지TC
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• 제44권8호
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• pp.51-61
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• 2007

신뢰할 수 있는 데이타 전송을 위해 3GPP RLC 명세서는 window 기반의 수락 제어 방식이 곁들어진 selective-repeat ARQ 방식을 채택하였다. 이러한 3GPP ARQ는 selective-repeat ARQ 부류에 속하고 따라서 재정렬 문제가 내재한다. 길고 불규칙한 재정렬 시간은 throughput 및 지연 성능의 열화를 불러오고 재정렬 버퍼의 범람을 초래할 수 있다. 또한 지연과 상실에 모두 민감한 서비스를 위해 재정렬 시간은 반드시 조절되어야 한다. 이러한 재정렬의 위해를 인지하고 3GPP ARQ의 원래 수락 제어 방식을 대체하여 재정렬 버퍼의 점유량을 억제하기 위한 snowball 방식을 제안한다. Snowball 방식은 재정렬 버퍼에 남아있는 기존의 DATA PDU에 인접하지 않은 새 DATA PDU를 거부하는 특징을 갖는다. 이러한 고의적 거부는 재정렬 버퍼의 점유량을 낮추는 반면 throughput 및 지연 성능을 악화시킬 수 있다. 따라서 해석적 근사 방법을 개발하여 snowball 방식이 포화 점유량 및 throughput 비치는 영향을 조사한다. 또한 모의 실험 방법으로 실제 환경에서 최고 점유량, 정규화된 throughput 그리고 평균 지연을 평가한다. 모의 실험 결과로부터 3GPP ARQ의 원래 수락 제어 방식에 비해 snowball 방식은 점유 및 throughput 성능을 모두 고양할 수 있음을 확인한다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 국제심포지움
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• pp.88.2-98
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• 2002

A wide arry of naturally occurring substances particularly those present in dietary and medicinal plants, have been reported to possess substantial cancer chemopreventive properties. Certain phytochemicals retain strong antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activities. Inducible cyclooxygenase(COX-2) and nitric oxide synthase (iNOS) are important enzymes that mediate inflammatory processes. There is some evidence that expression of both COX-2 and iNOS is co-regulated by the eukaryotic transcription factor NF-$textsc{k}$B. Increased expression of COX-2 and/or iNOS has been associated with pathophysiology of certain types of human cancers as well as inflammatory diseases. Since inflammation is closely linked to tumor promotion, substances with potent anti-inflammatory activies are anticipated to exert chemopreventive effects on carcinogenesis, particularly in the promotion stage. An example is curcumin, a yellow pigment of turmeric (Curcuma longa L., Zingiberaceae), that strongly occurring diaryl heptanoids structurally related to curcumin have substantial anti-tumor promotional activities in two-stage mouse skin carcinogenesis. Thus, yakuchinone A [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenyl-3heptanone] and yakuchinone B [1-(4'-hydroxy-3'methoxyphenyl)-7-phenylhept-1-en-3-one] present in Alpinia oxyphylla Miquel (Zingiberacease) attenuate phorbol ester-induced inflammation and papilloma formation in female ICR mice. These diarylheptanoids also suppressed phorbol ester-induced activation of epdermal ornithine decarboxylase and its mRNA expression when applied onto shaven backs of mice. Yakuchinone A and B as well as curcumin inhibited phorbol ester-induced expression of COX-2 and iNOS and their mRNA in mouse skin via inactivation of NF-$textsc{k}$B. Capsaicin, a major pungent ingredient of red pepper also attenuated phorbol ester-induced NF-$textsc{k}$B activation. Similar suppression of COX-2 and iNOS and down-regulation of NF-$textsc{k}$B activation for its DNA binding were observed with the ginsenosied Rg3 and the ethanol extract of Artemisia asiatica. We have also found that certain anti-inflammatory phytochemicals exert inhibitory effects on phorbol ester-induced COX-2 expression and NF-$textsc{k}$B activation in immortalized human breast epithelial (MCF-10A) cells in culture. One of the plausible mechanisms undelying inhibition by aforementioned phytochemicals of phorbol ester-induced NF-$textsc{k}$B activation involves interference with degragation of the inhibitory unit, I$textsc{k}$Ba, which blocks subsequent nuclear translocation of the functionally active p65 subunit of NF-$textsc{k}$B. the activation of epidermal NF-$textsc{k}$B by phorbol ester and subsequent induction of COX-2 hence appear to play an important role in intracellular signaling pathwasy leading to tumor promotion and targeted inhibition of NF-$textsc{k}$B may provide a new promising cancer chemopreventive strategy.

• 생명과학회지
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• 제27권3호
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• pp.361-369
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• 2017

미토콘드리아의 항상성은 미토콘드리아 생합성과 마이토파지(자가포식에 의한 미토콘드리아 분해)로 불리는 2가지 주요 과정들에 의해 정교하게 조절되고 있다. 지구성 운동 훈련에 반응하여 골격근에서 미토콘드리아 생합성에 관한 기전들은 잘 정립되어 있는 반면 지구성 운동 훈련 후 골격근의 마이토파지 조절 기전과 마이토파지와 미토콘드리아 생합성의 협응을 조절하는 기전은 아직 명확히 밝혀져 있지 않다. 최근 연구들에 의하면 지구성 운동 훈련은 골격근에서 미토콘드리아 생합성, 미토콘드리아 역동성, 미토콘드리아 분해와 관련된 유전인자들의 발현을 증가시킨다고 하였다. 하지만 골격근에서 자가포식이 억제되었을 경우, 지구성 운동 훈련에 의한 미토콘드리아 생합성과 관련된 지표들인 Cox IV와 citrate synthase의 증가는 상쇄되었다. 따라서 자가포식과 마이토파지는 골격근의 미토콘드리아 생합성에 중요한 역할을 하며 정반대되는 이 두 과정(이화 또는 동화작용)의 협응 과정이 지구성 운동 훈련에 반응하여 대사적 기능과 지구력 운동 수행능력을 향상시키는 것과 같은 골격근의 적응에 중요한 듯하다. 지구성 운동은 미토콘드리아의 일정한 숫자를 유지시키기 위해 미토콘드리아 생합성, 미토콘드리아의 융합과 분열, 자가포식/마이토 파지들의 각각의 과정들을 조절하는 것으로 여겨진다. 지구성 운동 훈련은 골격근에서 마이토파지를 활성화시켜 미토콘드리아 양과 질을 조절하여 늙고 건강하지 않은 미토콘드리아를 젊고 건강한 미토콘드리아로 교체시킬 수 있다. 이 총론에서 미토콘드리아 생합성과 마이토파지의 분자학적 기전과 서로 상반되는 이 두 과정간의 협응이 골격근의 지구성 훈련에 대한 세포적 적응에 관련한다는 내용이 논의될 것이다.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.39-47
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• 2010

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer's disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at $0.1{\mu}M$ of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A ($20{\mu}M$) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.

• 대한의생명과학회지
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• 제11권2호
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• pp.175-183
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• 2005

The two major isoflavones in soy, genistein and daidzein, are well known to prevent hormone-dependent cancers by their anti estrogenic activity. The exact molecular mechanisms for the protective action are, however, not provided yet. It has been reported that genistein and daidzein have a potential anticancer activity through their antiproliferative effect in many hormone-dependent cancer cell lines. Transforming growth $factor-\beta1(TGF-\beta1)$ has also been found to have cell growth inhibitory effect, especially in mammary epithelial cells. This knowledge led to a hypothetical mechanism that the soy isoflavones-induced growth inhibitory effect can be derived from the regulation of $TGF-\beta1$ and $TGF-\beta$ receptors. In order to test this hypothesis, the effects of the soy isoflavones at various concentrations and periods on the expression of $TGF-\beta1$and $TGF-\beta$ receptors were investigated by using Northern blot analysis in human breast carcinoma epithelial cell lines, an estrogen receptor positive cell line (MCF-7) and an estrogen receptor negative cell line (MDA-MB-231). As a result, only genistein has shown a profound dose-dependent effect on $TGF-\beta1$ expression in the $ER^+$ cell line within the range of doses tested, and the expression levels are correspondent to their inhibitory activities of cell growth. Moreover, daidzein showed down-regulated $TGF-\beta1$ expression at a low dose, the cell growth proliferation was promoted at the same condition. Therefore, antiproliferative activity of the soy isoflavones can be mediated by $TGF-\beta1$ expression, and the effects are mainly, if not all, occurred by ER dependent pathway. The expression of $TGF-\beta$ receptors was induced at a lower dose than the one for $TGF-{\beta}1$ induction regardless of the presence of ER, and the expression patterns are similar to those of the cell growth inhibition. These results indicated that the regulation of $TGF-\beta$ receptor expression as well, prior to $TGF-\beta1$ expression, may be involved in the antiproliferative activity of soy isoflavones. Little or no expression of $TGF-\beta$ receptors was found in the MCF-7 and MDA-MB-231 cells, suggesting refractory properties of the cells to growth inhibitory effect of the $TGF-\beta$. The soy isoflavones can seemingly restore the sensitivity of growth inhibitory responses to $TGF-\beta1$ by re-inducing $TGF-\beta$ receptors expression. In conclusions, our findings presented in this study show that the antitumorigenic activity of the soy isoflavones could be mediated by not only $TGF-\beta1$induction but $TGF-\beta$ receptor restoration. Thus, soy isoflavones could be good model molecules to develop new nonsteroidal antiestrogenic chemopreventive agents, associated with, regulation of $TGF-\beta$ and its receptors.

• BMB Reports
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• 제53권4호
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• pp.218-222
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• 2020

Excessive and hyperactive osteoclast activity causes bone diseases such as osteoporosis and periodontitis. Thus, the regulation of osteoclast differentiation has clinical implications. We recently reported that dehydrocostus lactone (DL) inhibits osteoclast differentiation by regulating a nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), but the underlying mechanism remains to be elucidated. Here we demonstrated that DL inhibits NFATc1 by regulating nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and nuclear factor-erythroid 2-related factor 2 (Nrf2). DL attenuated IκBα phosphorylation and p65 nuclear translocation as well as decreased the expression of NF-κB target genes and c-Fos. It also inhibited c-Jun N-terminal kinase (JNK) but not p38 or extracellular signal-regulated kinase. The reporter assay revealed that DL inhibits NF-κB and AP-1 activation. In addition, DL reduced reactive oxygen species either by scavenging them or by activating Nrf2. The DL inhibition of NFATc1 expression and osteoclast differentiation was less effective in Nrf2-deficient cells. Collectively, these results suggest that DL regulates NFATc1 by inhibiting NF-κB and AP-1 via down-regulation of IκB kinase and JNK as well as by activating Nrf2, and thereby attenuates osteoclast differentiation.

• 한국균학회지
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• 제26권4호통권87호
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• pp.450-457
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• 1998

Cryparin은 Cryphonectria parasitica의 세포벽에 풍부한 소수성 단백질에 속한다. cryparin은 비록 하나의 유전자에 의해 발현되지만 액체배양 후 48시간이 지나면 발현된 전체 유전자중에서 22%를 차지할 정도의 높은 발현 양상을 나타낸다. 또한 cryparin은 RNA mycovirus인 Cryphonectria hypovirus 1의 감염에 의해 발현이 현저히 억제되는 유전자로 알려졌다. 이미 지난 실험(Kim et al., 1999)에서 상동염색체간의 재조합을 이용하여 cryparin 유전자를 항생제 hygromycin B 저항성 유전자로 치환한 치환체를 제조하였다. 발현율이 매우 높으면서도 virus에 의해 밀접하게 영향받는 cryparin 유전자의 promoter 분석을 위하여서는 대상이 되는 유전자 치환을 위한 vector만을 포함하며, 분석에 이용될 여러 유전자 운반체들이 어느 한곳에만 삽입되도록 하는 성질을 가진 균주의 개발이 필요하다. 그러나 지난번 실험의 결과 얻어진 cryparin 치환체는 치환용 vector외에도 무작위로 삽입된 vector가 존재하고 나아가 새로운 vector들이 어느 한곳에만 삽입되도록 하는 성질을 갖지 못하였다. 따라서 본 실험에서는 cryparin 유전자 치환체와 영양요구성 돌연변이체인 균주간의 교잡을 이용하여 분석 대상이 되는 유전자의 치환에 이용된 vector만을 포함하며, 분석에 이용될 여러 유전자 운반체들이 genome내의 어느 한곳에만 삽입되도록 하는 성질을 가진 균주를 제조하였다.