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        Serum- and glucocorticoid-inducible kinase 1 (SGK1) controls Notch1 signaling by downregulation of protein stability through Fbw7 ubiquitin ligase.

        Mo, Jung-Soon,Ann, Eun-Jung,Yoon, Ji-Hye,Jung, Jane,Choi, Yun-Hee,Kim, Hwa-Young,Ahn, Ji-Seon,Kim, Su-Man,Kim, Mi-Yeon,Hong, Ji-Ae,Seo, Mi-Sun,Lang, Florian,Choi, Eui-Ju,Park, Hee-Sae Cambridge University Press 2011 Journal of cell science Vol.124 No.1

        <P>Notch is a transmembrane protein that acts as a transcriptional factor in the Notch signaling pathway for cell survival, cell death and cell differentiation. Notch1 and Fbw7 mutations both lead the activation of the Notch1 pathway and are found in the majority of patients with the leukemia T-ALL. However, little is known about the mechanisms and regulators that are responsible for attenuating the Notch signaling pathway through Fbw7. Here, we report that the serum- and glucocorticoid-inducible protein kinase SGK1 remarkably reduced the protein stability of the active form of Notch1 through Fbw7. The protein level and transcriptional activity of the Notch1 intracellular domain (Notch1-IC) were higher in SGK1-deficient cells than in SGK1 wild-type cells. Notch1-IC was able to form a trimeric complex with Fbw7 and SGK1, thereby SGK1 enhanced the protein degradation of Notch1-IC via a Fbw7-dependent proteasomal pathway. Furthermore, activated SGK1 phosphorylated Fbw7 at serine 227, an effect inducing Notch1-IC protein degradation and ubiquitylation. Moreover, accumulated dexamethasone-induced SGK1 facilitated the degradation of Notch1-IC through phosphorylation of Fbw7. Together our results suggest that SGK1 inhibits the Notch1 signaling pathway via phosphorylation of Fbw7.</P>

      • SCOPUSKCI등재

        한국의 Amatoxins 중독증

        안영민,이동수,이강문,강상범,양진모,박영민,이영석,정규원,선희식,박두호,노현주,강영모,이종명,허정욱,최성곤,김정호,이상인,최승옥,최홍엽,권오선,구창덕,석순자,김양섭 대한간학회 2000 Clinical and Molecular Hepatology(대한간학회지) Vol.6 No.3

        한국의 amatoxins 중독증은 강원 영서 지역이 호발지역으로 알려져 왔으며 최초로 보고된 원인버섯은 알광대버섯이었으나 현재까지 재 확인된 바가 없다. 원인버섯이 확인된 예로는 강원 영서지역이나 대전지역의 독우산광대버섯과 함께 1998년 경북 일원에서 발생한 집단 중독사고의 개나리광대버섯과 대전에서 발생한 1예에서 흰알광대버섯을 들 수 있다. 최근까지 amatoxins 중독증에 관해 보고된 국내의 문헌을 살펴보면 한국에서 발생하는 amatoxins중독증은 사망률에서 외국의 20-40% 와 큰 차이가 있는 것 처럼 보이나 사실상 전체적인 발생빈도나 사망률 등을 산출한 예가 없었을 뿐아니라, 높은 사망률의 원인이 무엇인지를 비교하는 것도 불가능하였다. 저자들은 국내에서 발생하는 amatoxins 중독증의 예방과 보다 효율적인 진단 및 치료를 위해 발생빈도나 사망률 및 원인버섯 등의 기초적인 조사와 함께 문헌을 통해 amatoxins 중독증에 대한 지견을 고찰하고자 하였다. 대상과 방법: 1999년 1년간 원인버섯 식별을 위해 의뢰되었던 증례들과 연례적 호발지역의 의료기관에서 병력 및 임상소견으로 amatoxins 중독증으로 진단 또는 추정된 증례들을 조사하였다. 원인버섯의 식별은 발생지역을 방문하여 원인버섯의 확보가 가능했던 소수의 증례에서는 외관과 현미경적 소견으로 원인버섯을 식별하였으며 원인버섯의 확보가 불가능한 증례에서는 특징적인 외관으로 추정되었다. 결과: 54명의 대상환자들 중 43명에서amatoxins 중독증으로 진단되었으며 그중 35명은 중등도 이상의 중독증으로 간주하였다. 중등도 이상의 중독증에서는 7명이 사망하여 20%의 사망률을 나타내었으며 원인버섯은 독우산광대버섯과 개나리광대버섯이 확인되었다. 흰알광대버섯은 확인되지 않았으나 사실상 독우산광대버섯과의 감별은 이루어지지 않았다. 4예에서는 원인버섯이 확인되지 않아 더 연구 되어야 한다. 사망례에서는 비사망군에 비해 혈소판이 유의하게 감소한 소견을 보였다. 전예에서 간이식등의 치료는 시행되지 않았으며 대부분 수액요법을 근간으로한 보존요법을 실시하였다. 결론: 한국의 amatoxins 중독증은 주로 강원 영서지역과 경북 일원에서 호발하고, 원인버섯은 외국과는 달리 독우산광대버섯과 개나리광대버섯이 주된 원인버섯이며, 1997년 까지의 증례보고를 대상으로한 70%의 사망률과는 달리 중등도 이상의 중독증례를 대상으로 하여도 사망률은 20%로 외국에 비해 높지 않다. 그러나 외국과 달리 간이식과 같은 보다 적극적인 치료를 시도한 예가 없는데, 대부분 갑자기 나빠지기 때문에 준비를 못하는 것이 원인이다. 따라서, 사망률을 더 낮추기 위해서는 혈액이나 소변과 같은 체액에서 단시간 내에 amatoxins을 측정할 수 있는 임상 검사법이 개발되어 조기 진단이 가능해져야 하며, 중독 초기에 나쁜 예후가 예측되는 심각한 증례를 선별하여 전문적인 치료를 받을 수 있는 기회를 제공해야 한다. 아울러 amatoxins 중독증에 대한 보다 정확한 통계를 산출하여야 할 것이다. 저자들은 본 연구에 1999년도에 발생한 대부분의 amatoxins 중독증의 증례가 포함되었으나 포함되지 않은 증례들이 다수 있다고 생각한다. 이러한 기초 조사를 철저히 하기 위해서는 전국 각지에서 발생하는 버섯중독 사고를 의뢰 또는 신고 할 수 있는 일원화 된 창구가 필요하리라고 사료된다. $quot;Background/Aims: From the review of Korean literature most fatal mushroom poisonings have been due to amatoxins with high mortality. So far there have never been investigations on the amatoxins poisonings such as annual incidence, mortality, common causal species, and endemic areas. This study was carried out to develop some basic statistics as part of studies for an effective management of amatoxins intoxications. Method: For the year 1999 authors collected cases of mushroom poisonings which had been mainly gathered from hospitals nation-wide. All of the cases with suggestive amatoxins poisonings were screened by symptomatology and laboratory findings. The causal species of mushrooms were identified grossly and microscopically. Results: A total of 54 victims with mushroom poisonings were evaluated. The causal mushroom toxins were diagnosed or strongly suggested as amatoxins in 43 of 54 victims. Eleven of 54 victims did not conform to the category of amatoxins intoxication due to absent or minimal elevation of aminotransferase. Mean age of the victims was 44.3 23.3 (range: 7-78) with male predominance (1.2 : 1). The causal species were confirmed, or strongly suggested, as Amanita virosa in 25 victims, Amanita subjunquillea in 14, and unknown species in 4. Thirty-five out of a total of 43 were regarded as moderate to severe intoxication (AST or ALT $gt; 1,000 IU/L) with 20% mortality. Most fatal victims showed marked thrombocytopenia (40,000 19,000/mm3) compared to non-fatal victims (109,066 42,245/mm3). A total of 88.4% of victims was developed in the Kangwon and Kyungpuk provinces. Both are west of the Taebaek Mountains (38/43). Conclusions: Although the common causal species for amatoxins poisonings in Korea are different from European countries and North America, the mortality is similar to that of those areas. In order to further reduce the mortality, bedside diagnostic methods using biological fluids and more effective herapy for liver failure should be established$quot;.

      • SCISCIESCOPUS

        HIF-1α and HSP90: target molecules selected from a tumorigenic papillary thyroid carcinoma cell line.

        Mo, Ji-Hun,Choi, Ik J,Jeong, Woo-Jin,Jeon, Eun-Hui,Ahn, Soon-Hyun Japanese Cancer Association 2012 Cancer Science Vol.103 No.3

        <P>It is important to properly identify aggressive tumors among differentiated thyroid cancers that are most often indolent. By comparison of a tumorigenic clone with an originally less tumorigenic papillary thyroid carcinoma (PTC) cell line, we looked for markers involved in the aggressive biology of thyroid cancer. Human PTC cell lines BHP10-3 and its tumorigenic subclone BHP10-3SC(mice) were compared using microarray analysis. Upregulated genes in the tumorigenic clone were selected for RT-PCR, immunoblot analysis and immunohistochemistry in human tissue. Hypoxia-inducible factor (HIF)-1α and its chaperone protein heat shock protein (HSP)90 showed significantly increased expression in BHP10-3SC(mice) and human PTC tissue. These two genes, HIF-1α and HSP90, were further validated using siRNA gene knockdown, pharmacological inhibition using 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of both HSP90 and HIF-1α and in vivo orthotopic animal model. Invasiveness of BHP10-3SC(mice) was abrogated by blockade of HIF-1αin vitro by both siRNA and 17-AAG. The same finding was demonstrated in the orthotopic animal model. These findings support that HIF-1α is important in tumorigenesis of PTC and that it may serve to be an important target for identification and treatment of aggressive tumors.</P>

      • SCOPUSKCI등재

        Effects of Silkworm Extract on Disaccharidase Activities of Small Intestine and Blood Glucose-Lowering in C57BL/6J Mice

        Ahn, Jung-Mo,Hong, Jung-Hee,Kim, Mi-Lim,Lee, In-Seon,Rhee, Soon-Jae The Korean Society of Food Science and Nutrition 2005 Preventive Nutrition and Food Science Vol.10 No.1

        This study examined the anti-diabetic effect of a silkworm extract in C57BL/6J mice, an ob/㏈ model, fed a high fat diet for 8 weeks. The body weight was not significantly different with the silkworm-extract supplement, nor did food intake and body weight gains also did not differ significantly among the high-fat diet groups. However, the water intake by the silkworm-extract supplemented groups increased significantly compared with that by the distilled-water supplement group, nonetheless, the FER did not differ significantly. For all groups, the blood glucose increased the most after 30 minutes and yet returned to a fasting level within 90 minutes. The fasting time and resulting glucose tolerance for the silkworm-extract supplemented groups were significantly decreased compared to that for the high fat diet with distilled water supplement group, while the level of blood glucose in silkworm-extract supplemented groups was significantly decreased compared with than in the diabetic control group. The HbA1c and insulin levels were no different among the groups. The sucrase and lactase activities in the proximal small intestine were significantly decreased in the silkworm-extract supplement groups compared to that in the diabetic control group. There was no significant difference in the glycogen contents in the liver and muscle among the groups. In conclusion, it was found that the silkworm-extract supplement repressed the disaccharidase activity in the small intestines mucosa of the C57BL/6J mice.

      • Notch1 modulates oxidative stress induced cell death through suppression of apoptosis signal-regulating kinase 1

        Mo, Jung-Soon,Yoon, Ji-Hye,Ann, Eun-Jung,Ahn, Ji-Seon,Baek, Hyeong-Jin,Lee, Hye-Jin,Kim, Seol-Hee,Kim, Yeong-Dae,Kim, Mi-Yeon,Park, Hee-Sae National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.17

        <P>Notch1 genes encode receptors for a signaling pathway that regulates various aspects of cell growth and differentiation; however, the role of Notch1 signaling in p38 mitogen-activated protein kinase (MAPK) signaling pathway is still not well defined. In this study, we found that Notch1 intracellular domain (Notch1-IC) prevents oxidative stress-induced cell death through the suppression of the Apoptosis signal-regulating kinase (ASK) 1 signaling pathway. Notch1-IC inhibited H<SUB>2</SUB>O<SUB>2</SUB>-induced activation of ASK1 and the activation of downstream kinases in the p38 MAPK signaling cascade. The results of both in vivo binding and kinase studies have revealed that ASK1 is the direct target of Notch1-IC, whereas it produced no effect on either MAP kinase kinase (MKK) 3 or p38 MAPK. Notch1-IC blocked both the homooligomerization of ASK1 and inhibited ASK1 activity. Furthermore, Notch1-IC facilitated the translocation of activated ASK1 toward the nucleus. Notch1 knockdown was determined to be highly susceptible to oxidative stress-induced activation of ASK1-MKK3/MKK6-p38 MAPK signaling cascade and cell death. Taken together, our findings suggest that Notch1-IC may act as a negative regulator in ASK1 signaling cascades.</P>

      • Design of Ubiquitous Home Gateway and Intuitive User Interfaces for Home Appliances

        Kwang-Soon Choi,Yang-Keun Ahn,Young-Choong Park,Kwang-Mo Jung 대한전자공학회 2008 ICEIC:International Conference on Electronics, Inf Vol.1 No.1

        In this paper, we propose architecture of a ubiquitous home gateway and a new user interface mechanism. Ubiquitous home gateway is designed to adopt a new switch chip especially designed for exchanging data among heterogeneous networks and also designed to adopt Common Communication Protocol (CCP), an international standard for guaranteeing the interoperability and interconnectivity among home appliances in ubiquitous home network environments where various kinds of networks coexist with each other inherently. New intuitive user interface is one of key factors for home network users to utilize home network equipments and services easily. Functions of ubiquitous home gateway system and new user interface mechanism are verified through experimental home network service scenarios by interconnecting home network devices.

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