• Biomolecules & Therapeutics
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• 제32권1호
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• pp.115-122
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• 2024

Heat shock protein (HSP) 90 is expressed in most living organisms, and several client proteins of HSP90 are necessary for cancer cell survival and growth. Previously, we found that HSP90 was cleaved by histone deacetylase (HDAC) inhibitors and proteasome inhibitors, and the cleavage of HSP90 contributes to their cytotoxicity in K562 leukemia cells. In this study, we first established mouse xenograft models with K562 cells expressing the wild-type or cleavage-resistant mutant HSP90β and found that the suppression of tumor growth by the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was interrupted by the mutation inhibiting the HSP90 cleavage in vivo. Next, we investigated the possible function of thioredoxin interacting protein (TXNIP) in the HSP90 cleavage induced by SAHA. TXNIP is a negative regulator for thioredoxin, an antioxidant protein. SAHA transcriptionally induced the expression of TXNIP in K562 cells. HSP90 cleavage was induced by SAHA also in the thymocytes of normal mice and suppressed by an anti-oxidant and pan-caspase inhibitor. When the thymocytes from the TXNIP knockout mice and their wild-type littermate control mice were treated with SAHA, the HSP90 cleavage was detected in the thymocytes of the littermate controls but suppressed in those of the TXNIP knockout mice suggesting the requirement of TXNIP for HSP90 cleavage. We additionally found that HSP90 cleavage was induced by actinomycin D, β-mercaptoethanol, and p38 MAPK inhibitor PD169316 suggesting its prevalence. Taken together, we suggest that HSP90 cleavage occurs also in vivo and contributes to the anti-cancer activity of various drugs in a TXNIP-dependent manner.

• Journal of Microbiology and Biotechnology
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• 제34권2호
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• pp.407-414
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• 2024

Phosphorus is an essential but non-renewable nutrient resource critical for agriculture. Luxury phosphorus uptake allows microalgae to synthesize polyphosphate and accumulate phosphorus, but, depending on the strain of algae, polyphosphate may be degraded within 4 hours of accumulation. We studied the recovery of phosphorus from wastewater through luxury uptake by an engineered strain of Synechocystis sp. with inhibited polyphosphate degradation and the effect of this engineered Synechocystis biomass on lettuce growth. First, a strain (∆phoU) lacking the phoU gene, which encodes a negative regulator of environmental phosphate concentrations, was generated to inhibit polyphosphate degradation in cells. Polyphosphate concentrations in the phoU knock-out strain were maintained for 24 h and then decreased slowly. In contrast, polyphosphate concentrations in the wild-type strain increased up to 4 h and then decreased rapidly. In addition, polyphosphate concentration in the phoU knockout strain cultured in semi-permeable membrane bioreactors with artificial wastewater medium was 2.5 times higher than that in the wild type and decreased to only 16% after 48 h. The biomass of lettuce treated with the phoU knockout strain (0.157 mg P/m²) was 38% higher than that of the lettuce treated with the control group. These results indicate that treating lettuce with this microalgal biomass can be beneficial to crop growth. These results suggest that the use of polyphosphate-accumulating microalgae as biofertilizers may alleviate the effects of a diminishing phosphorous supply. These findings can be used as a basis for additional genetic engineering to increase intracellular polyphosphate levels.

• 생명과학회지
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• 제21권8호
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• pp.1163-1167
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• 2011

과다한 음주는 알츠하이머 및 파킨슨 질병과 같은 각종 만성 퇴행성 뇌질환의 대표적인 원인 중 하나로 알려져 있다. 체내에 유입된 에탄올은 알코올 탈수소효소(alcohol dehydrogenase, ADH)에 의해 아세트알데히드로 대사된 후 다시 알데히드탈수소효소 2(aldehyde dehydrogenase 2, ALDH2)에 의해 아세트산으로 대사되어 배출된다. 에탄올의 대사과정 중에는 다량의 free radical이 생성되어 체내에서 산화적 스트레스를 유발하는 것으로 알려져 있고, 아세트알데히드는 활성산소를 생산하는 독성물질로 잘 알려져 있다. 본 연구에서는 8주간 에탄올에 노출된 Aldh2 knockout 마우스를 사용하여 ALDH2 효소 활성이 뇌 조직과 소변의 지질과산화에 미치는 영향에 대하여 살펴보았으며, 지질과산화 정도를 측정하기 위해 HPLC를 통한 TBARS 정도를 측정하였다. 연구결과, 마우스에서 만성 에탄올 섭취는 뇌 조직 TBARS 생성에 영향을 주지 않는 것으로 나타났으나, 소변 TBARS는 Aldh2 (-/-) 마우스에서 에탄올을 투여함에 따라 유의한 증가를 보였다(p<0.05). 본 연구 결과로부터 8주간 에탄올을 경구 투여한 마우스에서 ALDH2의 활성은 체내의 전반적인 활성산소 생성에는 중요하게 관여하는 것으로 보이지만 뇌조직에서의 활성산소 생성에는 영향을 주지 않는 것으로 보이며, 이는 에탄올 노출과 이에 따른 활성산소가 다양한 만성 뇌질환을 유발한다는 기존의 가설에서 ALDH2의 활성이 중요하게 관여하지 않을 가능성을 시사한다.

• 대한소아치과학회지
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• 제32권3호
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• pp.576-583
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• 2005

치아의 형성은 상피-간엽간의 상호작용을 통해 조절되어지는 복잡한 발생과정이다. 지금까지 치관의 발생에 관여하는 유전자 및 그들의 신호전달경로에 관한 연구는 다수 진행되어 왔지만 치근의 발생을 조절하는 기전에 대해서는 별로 알려진 것이 없다. 최근에 NFI-C knock out 생쥐에서 정상치관에 비정상적인 치근을 가지는 치아가 보고되었다. 본 연구의 목적은 NFI-C가 어떻게 치근의 형태와 상아모세포의 분화에 관여하는지를 규명하는 것이다. NFI-C knock out 생쥐의 치근 발생동안에 HERS의 역할을 연구하고자 cytokeratin 면역조직화학적방법과 치근상아질의 특성을 규명하기 위해 DSPP mRNA in-situ hybrydization법을 수행하였다. 1. NFI-C knock out 생쥐의 치근형성시 HERS의 역할 Wild type과 knock out type 모두에서 cytokeratin은 모든 HERS 세포들과 반응하였고, HERS와 법랑상피 사이의 양성반응세포들의 연속성은 치경부 부위에서 소실되었다. Knock out type에서 치근상아질이 침착된 후, cytokeratin 양성-HERS 세포들은 치경부에서 불규칙한 배열과 극성의 상실을 보였다. 2. NFI-C knock out 생쥐의 치근상아질의 특성 DSPP mRNA의 발현은 wild type에서 치관과 치근상아질의 상아모세포 모두에서 강한 발현을 보인 반면, knock out type에서는 치관부위 상아질의 상아모세포에서만 강한 발현을 보였다. 3. NFI-C knock out 생쥐의 치근 발생과정에서 HERS는 치관으로부터 정상적인 확장을 보인 반면, 치근부위에서의 상아 모세포 분화는 실패하였다. 위의 결과들로 보아 NFI-C는 치근형성 과정에서 상아모세포 분화에 중요한 역할을 하는 것으로 사료된다.

• Journal of Photoscience
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• 제9권2호
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• pp.494-496
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• 2002

Fluorouracil (FU) is well known to induce discoid lupus-like eruption at the sun exposure sites in Japan. It means the associations of UVB with drug induced DLE. It is still obscure which cytokines are involved in the development of DLE. To address the issue, we established a murine model of FU and UVB-induced discoid lupus and could show the Th1 dominant cytokine profiles in DLE model of TCR $\alpha$ chain KO mice treated with FU and UVB.

• Journal of Photoscience
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• 제9권2호
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• pp.470-471
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• 2002

It has been well documented that dermal irradiation by ultraviolet A (UVA) locally decreases the number of Langerhans cells and suppresses contact hypersensitivity of the skin. We found that topical irradiation of UVA to the eye systemically decreased the number of Langerhans cells (LC) in the dorsalskin and lymph nodes and elicited lymphocyte apoptosis in the latter tissues but not in the thymus. Optic nerve resection, but not ciliary ganglionectomy, eliminated the UVA-induced decrease in dermal Langerhans cells by a mechanism that was partially inhibited by hypophysectomy. The immunosuppressive effect of UVA was not observed in knockout mice lacking inducible-type of nitric oxide synthase (iNOS). These results suggested that topical irradiation of UVA to the eye induced immunosuppression via NO-dependet neuronal pathways.

• 지식정보인프라
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• 통권10호
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• pp.108-125
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• 2002

한림 심포지움의 개최 목적은 국내의 일차 유전자원인 자연상태의 동물, 식물, 미생물의 현지내외 보전과 이차 유전자원인 수정란, 인위적 변이종, knockout mutant, 형질전환 생물 등의 보전을 포괄적이고, 체계적이며, 장기적으로 관장하기 위하여 관련 DB를 정보화, 네트워크화함으로써 생물자원의 산업적 이용을 촉진할 수 있는 마스터플랜을 세우고, 국내 생물자원의 발굴, 보존, 분양, 연구, 산업적 이용 등을 체계적이고 효율적으로 진행하기 위한 생물다양성DB 및 네트워크 구축, 부처간 역할 분담과 협력체계 수립, 국가차원의 관련 정보의관리 및 이용체계를 확립하기 위한 중장기적이고 포괄적인 전략을 확립하기 위함이었다.

• Nuclear Engineering and Technology
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• 제41권5호
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• pp.715-722
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• 2009

A model to predict failure of designed-to-fail (dtf) fuel particles is discussed. The dtf fuel under study consisted of a uranium oxycarbide kernel coated with a single pyrocarbon seal coat. Coating failure was assumed to be due to fission gas recoil and knockout mechanisms and direct diffusive release of fission gas from the kernel, which acted to increase pressure and stress in the pyrocarbon layer until it ruptured. Predictions of dtf fuel failure using General Atomics' particle fuel performance code for HRB-17/18 and HFR-B1 irradiation tests were reasonably accurate; however, the model could not predict the failure for COMEDIE BD-1. This was most likely due to insufficient information on reported particle fuel failure at the beginning.

• Journal of Gastric Cancer
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• 제14권2호
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• pp.67-86
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• 2014

Gastric cancer is one of the most common cancers in the world. Animal models have been used to elucidate the details of the molecular mechanisms of various cancers. However, most inbred strains of mice have resistance to gastric carcinogenesis. Helicobacter infection and carcinogen treatment have been used to establish mouse models that exhibit phenotypes similar to those of human gastric cancer. A large number of transgenic and knockout mouse models of gastric cancer have been developed using genetic engineering. A combination of carcinogens and gene manipulation has been applied to facilitate development of advanced gastric cancer; however, it is rare for mouse models of gastric cancer to show aggressive, metastatic phenotypes required for preclinical studies. Here, we review current mouse models of gastric carcinogenesis and provide our perspectives on future developments in this field.

• IMMUNE NETWORK
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• 제2권2호
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• pp.65-71
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• 2002

The immunological mechanism of the responses to ultraviolet (UV) B radiation in mouse models were investigated by the suppression of contact hypersensitivity (CHS) and delayed type hypersensitivity (DTH), and susceptibility to infection. However, there are some differences in immune suppression according to the different models as well as the irradiation protocols. Therefore, this review focused on the differences in the suppressive effects on CHS and DTH, and susceptibility to infection in relation to the different in vivo models. Recent advances in cytokine knockout mice experiments have the reexamination of the role of the critical cytokines in UVB-induced immune suppression, which was investigated previously by blocking antibodies. The characteristics of the suppressor cells responsible for UVB-induced tolerance were determined. The subcellular mechanism of UVB-induced immune suppression was also explained by the induction of apoptotic cells through the Fas and Fas-ligand interaction. The phagocytosis of the apoptotic cells is believed to induce the production of the immune suppressive cytokine like interleukin-10 by macrophages. Therefore, the therapeutic UVB response to a skin disease, such as psoriasis, by the depletion of infiltrating T cells could be considered in the extension line of apoptosis and immune suppression.