The critical role played by endotoxin-induced liver autophagy in the maintenance of lipid metabolism during sepsis

Chung, Ki Wung,Kim, Kyung Mok,Choi, Yeon Ja,An, Hye Jin,Lee, Bonggi,Kim, Dae Hyun,Lee, Eun Kyeong,Im, Eunok,Lee, Jaewon,Im, Dong Soon,Yu, Byung Pal,Chung, Hae Young Informa UK (TaylorFrancis) 2017 AUTOPHAGY Vol.13 No.7

<P>Macroautophagy/autophagy is a central mechanism by which cells maintain integrity and homeostasis, and endotoxin-induced autophagy plays important roles in innate immunity. Although TLR4 stimulation mediated by lipopolysaccharide (LPS) also upregulates autophagy in hepatocytes and liver, its physiological role remains elusive. The objective of this study was to determine the role of LPS-induced autophagy in the regulation of liver lipid metabolism. LPS treatment (5 mg/kg) increased autophagy, as detected by LC3 conversion and transmission electron microscopy (TEM) analysis in C57BL6 mouse livers. AC2F hepatocytes also showed increased autophagic flux after LPS treatment (1 mu g/ml). To investigate the role of LPS-induced autophagy further, liver lipid metabolism changes in LPS-treated mice and fasted controls were compared. Interestingly, LPS-treated mice showed less lipid accumulation in liver than fasted mice despite increased fatty acid uptake and lipid synthesis-associated genes. In vitro analysis using AC2F hepatocytes demonstrated LPS-induced autophagy influenced the degradation of lipid droplets. Inhibition of LPS-induced autophagy using bafilomycin A(1) or Atg7 knockdown significantly increased lipid accumulation in AC2F hepatocytes. In addition, pretreatment with chloroquine aggravated LPS-induced lipid accumulation and inflammation in C57BL6 mouse livers. The physiological importance of autophagy was verified in LPS-treated young and aged rats. Autophagic response was diminished in LPS-treated aged rats and lipid metabolism was impaired during sepsis, indicating autophagy response is important for regulating lipid metabolism after endotoxin challenge. Our findings demonstrate endotoxin-induced autophagy is important for the regulation of lipid metabolism, and suggest that autophagy helps maintain lipid metabolism homeostasis during sepsis.</P>

Age-related sensitivity to endotoxin-induced liver inflammation: Implication of inflammasome/IL-1β for steatohepatitis

Chung, Ki Wung,Lee, Eun Kyeong,Kim, Dae Hyun,An, Hye Jin,Kim, Nam Deuk,Im, Dong Soon,Lee, Jaewon,Yu, Byung Pal,Chung, Hae Young BLACKWELL PUBLISHING 2015 AGING CELL Vol.14 No.4

<P>Aging is associated with increased vulnerability to inflammatory challenge. However, the effects of altered inflammatory response on the metabolic status of tissues or organs are not well documented. In this study, we present evidence demonstrating that lipopolysaccharide (LPS)-induced upregulation of the inflammasome/IL-1β pathway is accompanied with an increased inflammatory response and abnormal lipid accumulation in livers of aged rats. To monitor the effects of aging on LPS-induced inflammation, we administered LPS (2 mg kg<SUP>−1</SUP>) to young (6-month old) and aged (24-month old) rats and found abnormal lipid metabolism in only aged rats with increased lipid accumulation in the liver. This lipid accumulation in the liver was due to the dysregulation of PPARα and SREBP1c. We also observed severe liver inflammation in aged rats as indicated by increased ALT levels in serum and increased Kupffer cells in the liver. Importantly, among many inflammation-associated factors, the aged rat liver showed chronically increased IL-1β production. Increased levels of IL-1β were caused by the upregulation of caspase-1 activity and inflammasome activation. <I>In vitro</I> studies with HepG2 cells demonstrated that treatment with IL-1β significantly induced lipid accumulation in hepatocytes through the regulation of PPARα and SREBP1c. In summary, we demonstrated that LPS-induced liver inflammation and lipid accumulation were associated with a chronically overactive inflammasome/IL-1β pathway in aged rat livers. Based on the present findings, we propose a mechanism of aging-associated progression of steatohepatitis induced by endotoxin, delineating a pathogenic role of the inflammasome/IL-1β pathway involved in lipid accumulation in the liver.</P>

Molecular Delineation of gamma-Ray-Induced NF-kappaB Activation and Pro-inflammatory Genes in SMP30 Knockout Mice.

Chung, Sang Woon,Kim, Ji Min,Kim, Dae Hyun,Kim, Ji Young,Lee, Eun Kyeong,Anton, Stephen,Jeong, Kyu Shik,Lee, Jaewon,Yoo, Mi Ae,Kim, Young Jin,Yu, Byung Pal,Chung, Hae Young Academic Press 2010 Radiation research Vol.173 No.5

<P>Exposure to gamma radiation causes a wide variety of biological damages and alterations, including oxidative stress. Among the key cellular components that are exquisitely sensitive to oxidative stress is the transcription factor nuclear factor (NF)-kappa B, which plays a central role in the activation of various pro-inflammatory genes. Recently, senescence marker protein 30 (SMP30), which has been used as an aging marker, was shown to have an antioxidant property. In the current study, using SMP30 knockout (SMP30(-/-)) mice that are vitamin C-deficient, we explored the effect of radiation on the activation of NF-kappa B and several key pro-inflammatory genes. Six groups of mice were studied. Group I mice were not irradiated and were supplemented with vitamin C (2.5 mg/kg/day). Group 2 mice were irradiated and were not supplemented with vitamin C. Group 3, 4 and 5 mice were irradiated with 1, 3 and 5 Gy of gamma radiation ((60)Co), respectively, without vitamin C supplementation. The wild-type mice (SMP30(+/+)) in group 6 were not irradiated or supplemented. At 24 h after irradiation, mice were killed humanely and the kidneys were removed analysis. The results showed that gamma radiation induced oxidative stress with corresponding NF-kappa B activation; this activated NF-kappa B led to the up-regulation of several major pro-inflammatory mediators such as COX-2, iNOS, VCAM1, ICAM1 and E-selectin in irradiated groups with no vitamin C supplementation. Our data provide molecular insights into mechanisms through which gamma radiation enhances oxidative stress-induced inflammation by showing the activation of NF-kappa B signaling pathway in vitamin C-deficient SMP30(-/-) mice. In addition, our present study produced evidence that gamma radiation exerts its deleterious action by activating the inflammatory process that are known to be a major risk factor for many chronic diseases. Furthermore, our data revealed vitamin C may play an important protective role in attenuating the adverse gamma-radiation-induced adverse effects by suppressing adverse oxidative effects and pro-inflammatory mediators. (C) 2010 by Radiation Research Society</P>

레이저 하이브리드 나노잉크 프린팅과 플렉서블 일렉트로닉스

정재원(Jaewon Chung) 대한기계학회 2005 대한기계학회 춘추학술대회 Vol.2005 No.5

There are many applications that require the delivery of small quantities of functional materials into locations on a substrate in the form of liquid solution. Inkjet printing technique satisfies these requirements and interest for nongraphical inkjet printing is growing. In addition, a higher resolution for printing flexible electronics is becoming more critical to enhance the performance of printing electronics. Since the resolution of inkjet printing process is limited, hybrid inkjet printing has gained interests. In this work, surface monolayer protected gold nanoparticles were printed in a liquid solution form and cured to make electrically conductive microlines on glass or polymer substrate at a reduced temperature by laser irradiation. In addition, nanoparticle film was effectively removed by applying femtosecond laser, so that small feature size was obtained.

비중심부 식민지 민족의 자유주의, 민족주의 운동의 혼재와 사회주의로의 진화

정재원(Chung Jaewon) 한국슬라브유라시아학회 2012 슬라브학보 Vol.27 No.2

중앙아시아 시민사회: 신자유주의 국제경제, 권위주의 국가 그리고 체제전환기 시민사회

정재원(Jaewon Chung) 서울대학교 아시아연구소 2014 아시아리뷰 Vol.4 No.1

자동차 응축기용 다채널 편평관의 압력강하 및 열전달특성에 관한 실험

정재원(Jaewon. Chung),전창덕(C.D. Jeon),강신형(S.H. Kang),이진호(Jinho Lee) 대한설비공학회 1997 대한설비공학회 학술발표대회논문집 Vol.1997 No.6-1

타지키스탄 내전과 그 이후: 민족주의, 이슬람 그리고 민주주의

정재원 ( Jaewon Chung ) 서울대학교 러시아연구소 2016 러시아연구 Vol.26 No.1

본 논문은 이데올로기와 이슬람, 지역주의, 족벌(clan), 우즈벡 민족 문제등 다양한 요인들 중에서도 체제전환 및 내전, 그리고 종전 이후 국민 국가건설 등 최근까지의 타지크 정치사회적 변화의 핵심으로 타지크 민족주의 적 요소가 있었음을 강조하고자 한다. 즉 체제전환기와 내전에 이르는 기간자유주의 정치세력에서 이슬람주의 정치세력에 이르기까지 다양한 저항 세력의 공통적 분모는 타지크 민족주의였으며, 내전 이후 옛 공산정권과는 달리, 라흐몬의 권위주의 정부가 민족주의의 의제들 중 상당부분을 수용하면서 저항 세력들의 입지가 크게 약화된 측면이 있는 것이다. 그러나 이제 소련 체제 붕괴 시기 반공산 민주화의 핵심 이데올로기였던 자유주의와 민족주의는 각각 제도적 민주주의의 외피와 시장경제 발전 과정 속에서 이후 그 급진성을 상실하거나 국민 국가 건설 과정에서 라흐몬 권위주의 정권의 지배 이데올로기의 일부가 됨으로써 그 진보적 성격이 사라지는 운명을 맞이하고 있다. 지역과 족벌, 종교 등에 기반한 정치가 아니라 이념과 정책에 기반한 정치로 전환할 때만이 민주주의가 정착될 수 있다고 할 때, 독특한 발전의 길을 걸어 왔던 타지크 이슬람 정치 세력의 부침과 새로운 정치 세력의 등장 등에 대한 연구를 통해 이슬람 지역에서의 민주주의의 발전 가능성에 대한 전망을 해 보고자 한다. This article aims shed light on the Tajik nationalism among the other factors, such as ideologies, Islam, religion, clan, and Uzbek minority problems that has had strong influences on the political and social changes in Tajikistan after the collapse of Soviet Union, the civil war and nation-building so far. Throughout the period of transition and civil war, liberal and Islamist opposition parties-resistances have shared Tajik nationalism with each other. Since the end of the civil war, the opposition parties, including Islamic political party(Islamic Renaissance Party), have been weakened, because, unlike the former Communist Party, Rakhmon’s authoritarian regime have accommodated and adopted Tajik nationalism. However, liberalism and nationalism have lost their radical and progressive nature in the process of development of institutional democracy and market economy system and have become a part of the ruling ideologies by the Rakhmon’s authoritarian regime. It is said that democratic system can be improved and developed when it is based not on regionalism, clan, and religion, but on the idea and policy. In this context, through the study on the fate of the existing liberal and Islamic political parties and the appearance of the new political actors, the article try to forecast the passibility of development of the democracy in the Muslim countries.

레이저 가공기술을 이용한 고분자 표면의 유기적 결정화 제어

이재원(Jaewon Lee),정지혜(Jihae Chung),김양현(Yanghyun Kim),김일원(Il Won Kim),정하승(Haseung Chung) 대한기계학회 2010 대한기계학회 춘추학술대회 Vol.2010 No.5

중부·동남부 유럽 탈사회주의 국가들에서의 사회민주주의 정치세력의 발전과 분화

정재원(Jaewon Chung) 비판사회학회 2013 경제와 사회 Vol.- No.98

1990년대 공산화 이전 시장 경제와 의회민주주의 정치의 경험이 풍부했던 중부 유럽 국가들의 공산당들은 사회민주주의적 정당으로의 변신에 일정정도 성공함으로써, 역사적 사회민주주의 정당과의 경쟁에서 승리하고, 국가사회주의 체제의 붕괴를 주도한 자유주의 우파의 집권 기간 동안의 신자유주의적 체제전환 정책에 대한 대안 세력으로 거듭나면서, 체제 전환 이후 불과 수년도 지나지 않아 집권에 성공하기도 하였다. 반면, 공산화 이전 산업화와 민주 정치의 경험이 적었던 발칸 반도의 국가들에서는 역사적 사회민주주의 세력들은 매우 미약하거나 이행 국면에서 반공산주의적 자유주의-민족주의 진영에 합류하는 등 영향력 확대에 실패하면서 스스로 약화의 길을 자초하였고, 공산주의 후계정당들은 공공연한 사회민주당으로의 변신 선언과는 달리, 국가마다 다양한 상황 변화를 맞으면서 당내 보수적-민족주의적 분파가 주도권을 장악하여 구래의 현실 사회주의식(후견주의식) 사회경제정책을 유지하거나, 반민주적이고 민족주의 정당과 구별되지 않는 정당으로 변질되기도 한다. 이러한 탈사회주의 동유럽 국가들에서의 사회민주주의 세력들의 다양한 분화, 발전 과정과 그 한계는 근본적으로는 공산화 이전의 민주주의 정치와 시장경제의 경험의 유무, 공산화의 자발성 여부와 기간, 그리고 지역별 역사적, 종교적, 문화적 전통의 차이 등에 기인한다고 할 수 있다. 그러나 이러한 원인들과 더불어 간과하지 말아야 할 것은 이러한 차이와 분화는 신자유주의 세계화 과정 속에서 중심부 국가와 자본의 이해와 필요에 따라 선택적으로 세계자본주의 체제 속으로 편입되는 과정에서 강제된 결과이기도 하다는 것이다. 본 논문에서는 이러한 한계를 극복하고자 사회민주주의 세력의 분화를 역사적, 문화적 지리적 차원에서뿐 아니라, 세계자본주의 체제 속에서 파악하여, 특히 신자유주의 세계화 속에서 서구 국가와 자본의 분업 전략에 따른 이 지역 국민들의 다양한 적응과 저항의 기제가 사회민주주의 정치세력의 분화와 변질의 중요한 토대임을 밝혀내고자 한다. With the rise of globalization and the diffusion of neoliberal economic reform throughout the world, the relevance of partisanship for economic reform has become the subject of much controversy. After the fall of socialist system, countries in Central and Eastern Europe faced global economic pressures, but, they simultaneously needed to construct a market economy. In this situation, the social democratic parties in the region worked out cognate strategies of deciding the tasks in countries, where inhere beside the authorities or form a powerful opposition, combining the measures of market economy and of raising a cost-performance with the active social policy. In this context, author insists that the history of revival and prospects of parties of social-democratic orientation in the region is deeply related to the historical roots of dependences and the economic marginalization enforced by the core of capitalism in the West in the era of neoliberal globalization. Undoubtedly, it was found that historical and cultural factors were related to the emergence of post-communist-nationalist political cooperation or post-communist leftist-neoliberal combination. It, however, also has to be considered that the external power has played amount role in setting and enforcing political agendas for the states of the region and influenced domestic political outcomes. The present economic relations between Central and Southeastern Europe and the West are still patron-clientele or core-periphery relations. In Southeastern European countries, the patrimonial communist regimes produced communist successor parties which emerged as conglomerate parties with a very weak social democratic component, largely because the social democrats began in a very weak position. In Central Europe, however, communist successor parties were provided with organizational resources and a pool of political talents which enabled them to quickly adopt characteristics akin to a modern West European social democratic parties. Insofar as former communist regime parties reformed and adopted a social democratic platform, they won easy victories over historical social democratic parties. In this context, author analyses the criterion of typology of social-democratic parties in the region, the history of revival of these parties and the programs and some results of social democratic parties. The external factor forced post-communist countries to be integrated selectively into the world-capitalist system and make the social democratic parties become quite different. whatever the case, the support of statism, socialism, nationalism and (neo)liberalism mixed in together is likely to remain an important part of post-communist politics in the region.