인플라마솜 매개 peroxiredoxin2의 분비와 보체 고전경로 활성화

의과학과/석사Peroxiredoxins (Prxs)은 다양한 세포 구성 요소에서 발견되는 단백질이다. 세포 내에서 존재하는 Prxs은 활성산소를 제거하거나 활성산소에 의해 매개되는 신호전달을 억제하는 역할을 한다. 세포 내 Prxs의 역할은 이미 잘 알려져 있지만, 분비된 Prxs의 역할에 대해서는 많은 연구가 진행되어 있지 않다. 최근에 Prxs이 허혈성 뇌 증후군에서 분비되어 염증 반응을 유도하는 danger-associated molecular pattern (DAMP) 단백질로서 역할을 한다고 보고되었다. 본 연구에서는 허혈성 뇌 증후군과 같은 세포 괴사에 의한 분비뿐만 아니라 LPS 또는 LPS와 ATP처럼 염증반응을 유도하는 자극원에 의해서도 Prxs이 분비됨을 확인하였다. LPS와 ATP를 함께 이용한 자극은 면역세포에서 inflammasome (인플라마솜)을 활성화시키는 자극원으로 널리 알려져 있다. Inflammasome이 세포 내에서 형성된 후에는 caspase-1의 활성화에 의해 IL-1β가 잘리게 되고, 잘린 IL-1β는 세포 밖으로 분비되어 염증반응을 유도하는 사이토카인으로 작용하게 된다. Prx2의 분비가 실제로 inflammasome 형성에 의한 것인지 확인하기 위해 caspase-1 억제제를 처리하거나 NLRP3가 결손된 마우스 유래 세포에 LPS와 ATP로 자극하였을 때, Prx2의 분비가 감소함을 관찰하였다. Prx2와 보체의 상호작용을 통한 보체 활성화에 미치는 영향을 관찰한 결과 보체 고전경로의 개시자인 C1q와 결합하고 이후 보체 활성화를 통해 C4b 및 C5b-9의 형성을 유도함을 확인하였다. 본 연구를 통하여 세포 내 항산화 단백질인 Prx2가 inflammasome 매개 기전으로 분비되고 C1q 단백질과의 결합을 통해 보체 고전경로를 활성화시킴을 제시하는 바이다.ope

인플라마솜 매개 peroxiredoxin2의 분비와 보체 고전경로 활성화

의과학과/석사Peroxiredoxins (Prxs)은 다양한 세포 구성 요소에서 발견되는 단백질이다. 세포 내에서 존재하는 Prxs은 활성산소를 제거하거나 활성산소에 의해 매개되는 신호전달을 억제하는 역할을 한다. 세포 내 Prxs의 역할은 이미 잘 알려져 있지만, 분비된 Prxs의 역할에 대해서는 많은 연구가 진행되어 있지 않다. 최근에 Prxs이 허혈성 뇌 증후군에서 분비되어 염증 반응을 유도하는 danger-associated molecular pattern (DAMP) 단백질로서 역할을 한다고 보고되었다. 본 연구에서는 허혈성 뇌 증후군과 같은 세포 괴사에 의한 분비뿐만 아니라 LPS 또는 LPS와 ATP처럼 염증반응을 유도하는 자극원에 의해서도 Prxs이 분비됨을 확인하였다. LPS와 ATP를 함께 이용한 자극은 면역세포에서 inflammasome (인플라마솜)을 활성화시키는 자극원으로 널리 알려져 있다. Inflammasome이 세포 내에서 형성된 후에는 caspase-1의 활성화에 의해 IL-1β가 잘리게 되고, 잘린 IL-1β는 세포 밖으로 분비되어 염증반응을 유도하는 사이토카인으로 작용하게 된다. Prx2의 분비가 실제로 inflammasome 형성에 의한 것인지 확인하기 위해 caspase-1 억제제를 처리하거나 NLRP3가 결손된 마우스 유래 세포에 LPS와 ATP로 자극하였을 때, Prx2의 분비가 감소함을 관찰하였다. Prx2와 보체의 상호작용을 통한 보체 활성화에 미치는 영향을 관찰한 결과 보체 고전경로의 개시자인 C1q와 결합하고 이후 보체 활성화를 통해 C4b 및 C5b-9의 형성을 유도함을 확인하였다. 본 연구를 통하여 세포 내 항산화 단백질인 Prx2가 inflammasome 매개 기전으로 분비되고 C1q 단백질과의 결합을 통해 보체 고전경로를 활성화시킴을 제시하는 바이다.ope

고려 불교 의학의 한 단면 - 승려의 질병과 치료

This paper aims to research what kind of diseases the Buddhist monks had suffered and how they were cured in Buddhist seon monasteries(禪院), using the inscriptions of Buddhist National Priests(國師) and Royal Priests(王 師) in Goryeo Dynasty. From their life stories and achievements in the epitaphs, I found the descriptions of Balbae(發背：the abscess on the back), dysentery(痢疾) and chronic wind disease(風痾, stroke), etc.. I presume musculoskeletal disorders owing to excessive training. It depended on their social status for the cures. For the high Buddhist monks, the medical cares were provided by king, such as national priest and royal priest. For the common monks, there was a healing system and a specific place in the Buddhist seon monastery, where many monks and workers resided. It was called Yeon-su-dang(延壽堂：room for life extension). According to The Regulations of Seon Monastery(禪院淸規), published by Song(宋) China's Buddhist monk Cijue Zongze(慈覺宗賾, 910～1092) in 1103, there were several disciplines for sick monks in seon monastery. When the Buddhist monks got sick, they had to chant to Amitabha(阿彌陀佛), and took medicine out of duties in Yeon-su-dang. There were also some disciplines regarding how to die and how to arrange the funeral for dead Buddhist monk in the Regulations. From the inscriptions of the Buddhist monks in Goryeo, I discovered that the Regulations were strictly observed in seon monasteries for sick monks and funeral procedure.ope

Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the subtilases that promotes the internalization and degradation of LDL receptor in liver and thereby controls the level of LDL cholesterol in plasma. Here, we show that the expression of PCSK9 in HepG2 cells is completely dependent on the absence or presence of sterols. The minimal promoter region of the PCSK9 gene contains a sterol-regulatory element (SRE), which makes the transcription of PCSK9 dependent on sterols. Expression of nuclear forms of sterol-regulatory element binding protein-1 (SREBP-1) and SREBP-2 dramatically increased the promoter activity of PCSK9. In vitro-translated nuclear forms of SREBPs showed interactions with SRE, whereas mutations in SRE abolished their binding. In vivo studies in mice showed that Pcsk9 protein and mRNA were decreased significantly by fasting and increased by refeeding. However, supplementation with 2% cholesterol in the diet prevented the increase in Pcsk9. The amounts of Pcsk9 mRNA in livers of refed mice showed correlated regulation by the changes in the nuclear form of Srebp-2. In summary, it is suggested that the expression of PCSK9 is regulated by sterol at the transcriptional level in HepG2 cells and that both SREBP-1 and SREBP-2 can transcriptionally activate PCSK9 via SRE in its proximal promoter region in vitro. However, in vivo, it is suggested that the sterol-dependent regulation of PCSK9 is mediated predominantly by SREBP-2.ope

In silico Screening of Chemical Libraries to Develop Inhibitors That Hamper the Interaction of PCSK9 with the LDL Receptor

PURPOSE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low density lipoprotein receptor (LDLR) and promotes degradation of the LDLR. Inhibition of PCSK9 either by reducing its expression or by blocking its activity results in the upregulation of the LDLR and subsequently lowers the plasma concentration of LDL-cholesterol. As a modality to inhibit PCSK9 action, we searched the chemical library for small molecules that block the binding of PCSK9 to the LDLR. MATERIALS AND METHODS: We selected 100 chemicals that bind to PCSK9 where the EGF-AB fragment of the LDLR binds via in silico screening of the ChemBridge chemical library, using the computational GOLD algorithm analysis. Effects of chemicals were evaluated using the PCSK9-LDLR binding assay, immunoblot analysis, and the LDL-cholesterol uptake assay in vitro, as well as the fast performance liquid chromatography assay for plasma lipoproteins in vivo. RESULTS: A set of chemicals were found that decreased the binding of PCSK9 to the EGF-AB fragment of the LDLR in a dose-dependent manner. They also increased the amount of the LDLR significantly and subsequently increased the uptake of fluorescence-labeled LDL in HepG2 cells. Additionally, one particular molecule lowered the plasma concentration of total cholesterol and LDL-cholesterol significantly in wild-type mice, while such an effect was not observed in Pcsk9 knockout mice. CONCLUSION: Our findings strongly suggest that in silico screening of small molecules that inhibit the protein-protein interaction between PCSK9 and the LDLR is a potential modality for developing hypercholesterolemia therapeutics.ope

Streptomyces chromofuscus SMF28이 生成하는 cathepsin B 沮害物質의 特性

Thesis (doctoral)--서울대학교 대학원 :미생물학과,1999.Docto

A Case Study of Teaching Korean History in English in Korea

This paper is a report as well as a case study of teaching pre-modern Korean history in English by Korean teachers who have studied in Korea. The students who took these courses consisted of three different groups: American exchange students, Chinese students, and Korean students. Each of these groups showed varying interest based on their intellectual backgrounds. The American students exhibited more interest in interactive learning such as Korean traditional music and field trips to sites of various examples of Korean historical architecture, while the Korean and Chinese students found this architecture familiar and were not as enthusiastic as the American students. Regarding the three groups’ general responses to the course, the Chinese student were surprised to find China being depicted as invaders, while the Korean students were intrigued by different interpretations of their national history than they had been accustomed to. The American students, on the other hand, were quite unemotional concerning the various interpretations of Korean history. These reactions showed how ones’ perspective on history is heavily influenced by ones’ educational background. Overall, these courses were very interesting and helpful as they allowed both students and lecturers to widen their understanding of how Korean history is perceived and perpetuated by different academic societies.restrictio

A Design and implementation of expert system development tool using extended fuzzy reasoning method

Maste

금속 나노입자, 유무기 나노구조체 및 생체미네랄을 포함한 나노크기의 시스템의 제조와 분석과 응용

학위논문(박사)--서울대학교 대학원 :화학부,2007.Docto

The Ancient History of Korea Through Epidemics

This research aims to explore the ancient history of Korea through epidemics, specifically as recorded in Samguk-saki (三國史記). Since 2002, I have conducted a good deal of research concerning the epidemics and pandemics which occurred in Korea and other parts of East Asia during the time of the Three Kingdoms and Unified Silla. My research has brought to light several new pieces of information that historians have thus far overlooked Korea’s ancient history. First, I submit that many epidemics which occurred in ancient Korea broke out largely as a result of mass immigration and war. Second, in the 4th century, the new religion of Goguryeo, Buddhism, derived from the Northern and the Southern dynasties (南北朝) of China, brought new epidemics as well, which resulted in the Goguryeo people accepting Buddhism more rapidly. The same scenario played out in Japan, where the Buddhism was introduced by Baekje in the 6th century. Third, most of the pandemics in ancient Korea originated in China, and they sometimes spread from Korea to Japan. Fourth, some epidemics had political impact, as when an epidemic would take the life of a high-ranking or important figure, such as a king or political leader. For example, King Sunduck (宣德王:rg.780-785) died as the result of an epidemic, presumably smallpox. It was not only the king. Many aristocrats and members of the court were also killed at that time. There is no record of it, but that doesn’t mean it never happened. In ancient times, many people thought that epidemics were a punishment of Gods. Punishment from heaven would imply fault on the part of political leaders, who would in turn not want to record their shortcomings. As a result, Kim Kyungshin, King Wonsung (元聖王:rg.785-798), ascended the throne, even though another successor, Kim Jouwon(金周元), had already been chosen by the people of the court, including Qeen Jungui (貞懿太后), the daughter of King Sungduck (聖德王:rg.702-737) and the mother of King Sunduck. It appears that Kim Jouwon had fled from the smallpox, which was widespread in the court in 785. Kim Kyung-shin, however, was presumably more brave, waiting in the palace to inherit the throne as soon as King Sunduck died.prohibitio