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Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy
Jang Hyun-Jun,Lee Yo Han,Dao Tam,Jo Yunju,Khim Keon Woo,Eom Hye-jin,Lee Ju Eun,Song Yi Jin,Choi Sun Sil,Park Kieun,Ji Haneul,Chae Young Chan,Myung Kyungjae,Kim Hongtae,Ryu Dongryeol,Park Neung Hwa,Par 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Autophagy functions in cellular quality control and metabolic regulation. Dysregulation of autophagy is one of the major pathogenic factors contributing to the progression of nonalcoholic fatty liver disease (NAFLD). Autophagy is involved in the breakdown of intracellular lipids and the maintenance of healthy mitochondria in NAFLD. However, the mechanisms underlying autophagy dysregulation in NAFLD remain unclear. Here, we demonstrate that the hepatic expression level of Thrap3 was significantly increased in NAFLD conditions. Liver-specific Thrap3 knockout improved lipid accumulation and metabolic properties in a high-fat diet (HFD)-induced NAFLD model. Furthermore, Thrap3 deficiency enhanced autophagy and mitochondrial function. Interestingly, Thrap3 knockout increased the cytosolic translocation of AMPK from the nucleus and enhanced its activation through physical interaction. The translocation of AMPK was regulated by direct binding with AMPK and the C-terminal domain of Thrap3. Our results indicate a role for Thrap3 in NAFLD progression and suggest that Thrap3 is a potential target for NAFLD treatment.
장연주(Yeonju Jang),최승윤(SeongYune Choi),강윤지(Yunji Kang),김경상(Kyungsang Kim),김원유(Wonyou Kim),김정남(Jeongnam Kim),김학인(Hakin-In Kim),손지원(Son-Jee Won),장병철(Byeong-Cheol Jang),김한성(Han-Sung Kim),박광현(Kwang-Hyun Par 한국컴퓨터교육학회 2021 한국컴퓨터교육학회 학술발표대회논문집 Vol.25 No.1(A)
인공지능(AI) 교육에 대한 전 세계적 열기가 뜨거운 가운데, 우리나라에서는 AI 인재를 양성하기 위한 교육정책을 제시하였고 교육현장과 학계에서는 초등학생들부터 시작하는 AI 교육과정과 교육 자료를 제시하고 있다. 하지만 초등학교에서 교사들이 수업에 직접 활용할 수 있는 교수학습자료는 매우 부족한 실정이다. 따라서 본 연구에서는 초등 교사들이 효과적으로 AI 교육을 할 수 잇도록 프로그램을 개발하는 것을 목적으로 한다. 본 연구에서 개발한 교육 프로그램은 이론과 실습을 포괄하는 구성이며 AI의 윤리적인 이슈까지 포괄할 수 있도록 내용을 구성하였다. 학생들은 본 프로그램을 통하여 AI를 체험하고, AI의 원리에 대해 학습하며 블록코딩을 통한 실습을 할 수 있으며 교사들이 현장에서 바로 활용할 수 있도록 지도안과 활동 예시들을 함께 제공하였다.
Phellinus linteus, Phellinus baumii 및 Phellinus gilvus 자실체 추출물의 항암효과 비교
배재성(Jae-Sung Bae),황미현(Mi-Hyun Hwang),장광호(Kwang-Ho Jang),이만휘(Man-Hee Rhee),이근우(Keun-Woo Lee),조우식(Woo-Sik Jo),최성국(Sung-Kuk Choi),윤효인(Hyo-In Yun),임종환(Jong-Hwan Lim),김종춘(Jong-Choon Kim),박승춘(Seung-Chun Par 한국독성학회 2004 Toxicological Research Vol.20 No.1
This study was undertaken to investigate comparative anti-tumor activity of water extracts of Phellinus gilvus (PGE), Phellinus linteus (PLE), and Phellinus baumii (PBE) in vitro. The anti-tumor activity in the present study was evaluated by sulforhodamine B (SRB) and microtetrazolium (MTT) assay in terms of cell survival level. The tumor cells (sarcoma 180 and P388) were treated with PGE, PLE, and PBE (7.5, 15, and 30 mg/ml) and Doxorubicin (DOX) (0.001~10 mM). The results showed that DOX, PGE, and PLE inhibited proliferation showing a dose-dependent manner against both tumor cells. However, PBE was inhibited by the only 30 mg/ml in both cells proliferation. In conclusion, all of PGE, PLE, and PBE used in this study have shown anti-tumor activity against both sarcoma 180 and P388. Among them, PLE was the most effective in anti-tumor activity against sarcoma 180 (p<0.05) and PGE was against P388 in SRB assay. PLE, however, was against P388 (p<0.05) in MTT assay.
( Ae Rin Baek ),( Ji Min Lee ),( Hyun Jung Seo ),( Jong Sook Park ),( June Hyuk Lee ),( Sung Woo Park ),( An Soo Jang ),( Do Jin Kim ),( Eun Suk Koh ),( Soo Taek Uh ),( Yong Hoon Kim ),( Choon Sik Par 대한결핵 및 호흡기학회 2016 Tuberculosis and Respiratory Diseases Vol.79 No.3
Background: Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterized by the accumulation of excessive fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor β1 (TGF-β1).induced epithelial-to-mesenchymal transition (EMT) is thought to be a possible source of fibroblasts/ myofibroblasts in IPF lungs. We have previously reported that apolipoprotein A1 (ApoA1) has anti-fibrotic activity in experimental lung fibrosis. In this study, we determine whether ApoA1 modulates TGF-β1.induced EMT in experimental lung fibrosis and clarify its mechanism of action. Methods: The A549 alveolar epithelial cell line was treated with TGF-β1 with or without ApoA1. Morphological changes and expression of EMT-related markers, including E-cadherin, N-cadherin, and α-smooth muscle actin were evaluated. Expressions of Smad and non-Smad mediators and TGF-β1 receptor type 1 (TβRI) and type 2 (TβRII) were measured. The silica-induced lung fibrosis model was established using ApoA1 overexpressing transgenic mice. Results: TGF-β1.treated A549 cells were changed to the mesenchymal morphology with less E-cadherin and more N-cadherin expression. The addition of ApoA1 inhibited the TGF-β1.induced change of the EMT phenotype. ApoA1 inhibited the TGF-β1.induced increase in the phosphorylation of Smad2 and 3 as well as that of ERK and p38 mitogenactivated protein kinase mediators. In addition, ApoA1 reduced the TGF-β1.induced increase in TβRI and TβRII expression. In a mouse model of silica-induced lung fibrosis, ApoA1 overexpression reduced the silica-mediated effects, which were increased N-cadherin and decreased E-cadherin expression in the alveolar epithelium. Conclusion: Our data demonstrate that ApoA1 inhibits TGF-β1.induced EMT in experimental lung fibrosis.
방면호,장태오,송명종,김동현,권병목,김영국,이현선,정인식,김대근,김성훈,박미현,백남인,Bang, Myun-Ho,Jang, Tae-O,Song, Myoung-Chong,Kim, Dong-Hyun,Kwon, Byoung-Mog,Kim, Young-Kuk,Lee, Hyun-Sun,Chung, In-Sik,Kim, Dae-Keun,Kim, Sung-Hoon,Par 한국응용생명화학회 2004 Applied Biological Chemistry (Appl Biol Chem) Vol.47 No.2
식용식물자원으로부터 활성소재를 찾기 위하여 흰씀바귀 뿌리를 80% MeOH로 추출하고, 얻어진 추출물을 EtOAc, n-BuOH및 $H_2O$로 용매 분획하였다. EtOAc와 n-BuOH 분획에 대하여 column chromatography를 반복하여 4종의 화합물을 분리하였다. 각각에 대하여 2D-NMR을 포함한 스펙트럼 데이터의 해석과 문헌 자료를 조사하여 zaluzanin C (1), $9{\alpha}-hydroxyguaian-4(l5),10(14),11(13)-triene-6,12-olide$ (2), $3{\beta}-O-{\beta}-D-glucopyranosyl-8{\beta}-hydroxyguaian-4(15),\;10(14 )-diene-6,12-olide$ (3), $3-O-{\beta}- D-glucopyranosyl-8{\beta}hydroxyguaian-10(14)-ene-6,12-olide$ (4)로 구조를 결정하였다. 이들 화합물에 대하여 ACAT(Acyl-CoA: cholesterol acyltransferase), DGAT (diacylglycerol acyltransferase) 및 FPTase(farnesyl-protein transferase)의 활성에 미치는 억제효과를 측정하였다. Compound 1과 Compound 2는 DGAT에 대한 활성억제효과에 있어서 $IC_{50}$ 값이 각각 0.13 mM, 0.10 mM로 나타났고, FPTase에 대하여는 각각 0.15 mM, 0.18 mM로 나타났으며, ACAT에 대하여는 약한 억제 활성을 나타냈다. 따라서 흰씀바귀는 항암 및 항고혈압의 소재 개발에 있어서 유용한 자원으로 활용될 수 있을 것이다. The root of lxeris dentata forma albiflora was extracted with 80% aqueous MeOH and solvent fractionated with EtOAc, n-BuOH and water, successively. From the EtOAc and n-BuOH fractions, four sesquiterpene compounds were isolated through the repeated silica gel and ODS column chromatographies. The chemical structures were determined as zaluzanin C (1), $9{\alpha}-hydroxyguaian-4(l5),10(14),11(13)-triene-6,12-olide$ (2), $3{\beta}-O-{\beta}-D-glucopyranosyl-8{\alpha}-hydroxyguaian-4(15),10(14 )-diene-6,12-olide$ (3), and $3{\beta}-O-{\beta}- D-glucopyranosyl-8{\beta}hydroxyguaian-10(14)-ene-6,12-olide$ (4) through the interpretation of several spectral data including 2D-NMR. Some showed the inhibitory effects on DGAT (Diacylglycerol acyltransferase), ($IC_{50}$ values of 1, 2: 0.13, 0.10 mM), the catalyzing enzymes of the intracellular esterification of diacylglycerol and FPTase (Famesyl-protein transferase), ($IC_{50}$ values of 1, 2: 0.15, 0.18 mM), the farnesylation enzyme for Ras protein charge of cancer promotion.