Analysis of a Lung Defect in Autophagy-Deficient Mouse Strains

Heesun Cheong,Junmin Wu,Linda K. Gonzales,Susan H. Guttentag,Craig B. Thompson,Tullia Lindsten 한국실험동물학회 2015 한국실험동물학회 학술발표대회 논문집 Vol.2015 No.8

mTORC1 maintains metabolic balance

Cheong, Heesun,Klionsky, Daniel J Springer Science and Business Media LLC 2015 Cell research Vol.25 No.10

2015년 3차 약품개발연구소 세미나

정희선 ( Heesun Cheong ) 전남대학교 약품개발연구소 2015 약품개발연구지 Vol.24 No.-

Oncogenic Ras stimulates macropinocytosis, a clathrin-independent endocytosis that increases the uptake of extracellular fluid. However, the functional significance of and regulatory mechanisms driving macropinocytosis in cancer cells remain largely unknown. Here, we show that extracellular macromolecules, such as albumin, intermalized by Ras-expressing cells can support growth and survival under the nutrient-deprived conditions like those found in tumors. Moreover, we demonstrate that autophagy, a lysosome-mediated catabolic pathway, is required for the uptake and degradation of macropinocytic vesicles. Intracellular metabolites derived from macropinocytosis and autophagy directly influence the activity and localization of mTOR, which is ultimately responsible for the restoration of cell growth. Surprisingly, suppression of mTORC1, which typically triggers anabolic processes, facilitates macropinocytosis and thus supports cell growth and survival under the nutrientdeprived conditions. In a mouse xenograft model of pancreatic ductal adenocarcinoma, concomitant inhibition of macropinocytosis/autophagy and mTOR activity resulted in antitumor effects. These data suggest that novel anti-cancer strategies interrupting these metabolic processes and related signaling molecules may represent promising therapeutic avenues./

Nutritional Quality of Fermented Soy Foods in Thailand

Hyo-Sook Cheong,Heesun Choi,Ok-Ju Kang,Benya Manochai,Jeong Hwa Hong 한국식품영양과학회 2005 Preventive Nutrition and Food Science Vol.10 No.3

Soybean has been favored by many Thai people and it has been prepared by numerous different methods. Collected samples are as follows: Thua-nao paste from Chiangrai province, dried Thua-nao for Jatujak Market, Bangkok, 3 types of commercial soybean paste, soybean sauce and 2 types of fermented soybean curd cakes with other ingredients. Moisture contents of fresh and dried Thua-nao were 68.5 and 7.6%, respectively; therefore the shelf-life of dried Thua-nao can be extended to 1 year with proper packaging. The remainder of the soy foods had moisture contents of 55.4 to 64.4%. Fat contents of fresh and dried Thua-nao were 7.4 and 19.7%, respectively, whereas other samples contained less than 3%. Dried Thua-nao had the highest CHO (carbohydrates) content (37.4%); in contrast, soybean sauce contained only 4.5%. Calcium content was highest in dried Thua-nao followed by fresh Thua-nao; the other fermented soy foods had less than 44.7 mg/100 g. Salt was added to samples other than Thua-nao resulting in high Na contents. Free and total daidzein contents of dried Thua-nao were 355 and 676 ug/g; similarly free and total genistein contents were 293 and 616.5 ㎍/g, respectively.

Osterix represses adipogenesis by negatively regulating PPARγ transcriptional activity

( Younho Han ),( Chae Yul Kim ),( Heesun Cheong ),( Kwang Youl Lee ) 전남대학교 약품개발연구소 2016 약품개발연구지 Vol.25 No.-

Osterix is a novel bone-related transcription factor involved in osteoblast differentiation, and bone maturation. Because a reciprocal relationship exists between adipocyte and osteoblast differentiation of bone narrow derived mesenchymal stem cells, we hypothesized that Osterix might have a role in adipogenesis. Ablation of Osterix enhanced adipogenesis in 3T3-L1 cells, whereas overexpression suppressed this process and inhibited the expression of adipogenic markers including CCAAT/enhancer-binding protein alpha(C/EBPα) and peroxisome proliferator-activated receptor gamma(PPARγ). Further studies indicated that Osterix significantly decreased PPARγ-induced transcriptional activity. Using co-immunoprecipitation and GST-pull down analysis, we found that Osterix directly interacts With PPARγ. The ligand-binding domain(LBD)of PPARγ was responsible for this interaction, which was followed by repression of PPARγ-induced transcriptional activity, even in the presence of rosiglitazone. Taken together, we identified the Osterix has an important regulatory role on PPARγ activity, which contributed to the mechanism of adipogenesis.

REP1 Modulates Autophagy and Macropinocytosis to Enhance Cancer Cell Survival

Choi, Jungwon,Kim, Hyena,Bae, Young Ki,Cheong, Heesun MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.9

<P>Rab escort protein 1 (REP1), a component of the Rab geranyl-geranyltransferase 2 complex, plays a role in Rab protein recruitment in proper vesicles during vesicle trafficking. In addition to having well-known tissue degenerative phenotypes in the REP1 mutant, REP1 is tightly associated with cancer development and contributes to cell growth and survival. However, the functional mechanism of REP1 in cancer progression is largely uninvestigated. Here, we show that REP1 plays a crucial role in regulating mammalian target of rapamycin (mTOR) signaling and its downstream pathways, as well as autophagy and macropinocytosis, which are essential for cancer cell survival during metabolic stresses including starvation. REP1 small interfering RNA (siRNA) treatment downregulates mTORC1 activity in growing media, but blocks autophagosome formation under nutrient-depleted conditions. In contrast to the mild decrease of lysosomal enzyme activity seen in REP1 depletion, in REP1 knockdown the subcellular localization of lysosomes is altered, and localization of REP1 itself is modulated by intracellular nutrient levels and mTOR activity. Furthermore, REP1 depletion increases macro pinocytosis which may be a feedback mechanism to compensate autophagy inhibition. Concomitant treatment with macropinocytosis inhibitor and REP1siRNAresults in more significant cell death than autophagy blockade with REP1 knockdown. Therefore, REP1-mediated autophagy and lysosomal degradation processes act as novel regulatory mechanisms to support cancer cell survival, which can be further investigated as a potential cancer-targeting pathway.</P>

Tandem-multimeric F3-gelonin fusion toxins for enhanced anti-cancer activity for prostate cancer treatment

Shin, Meong Cheol,Min, Kyoung Ah,Cheong, Heesun,Moon, Cheol,Huang, Yongzhuo,He, Huining,Yang, Victor C. Elsevier/North Holland 2017 International journal of pharmaceutics Vol.524 No.1

<P><B>Abstract</B></P> <P>Despite significant progress in prostate cancer treatment, yet, it remains the leading diagnosed cancer and is responsible for high incidence of cancer related deaths in the U.S. Because of the insufficient efficacy of small molecule anti-cancer drugs, significant interest has been drawn to more potent macromolecular agents such as gelonin, a plant-derived ribosome inactivating protein (RIP) that efficiently inhibits protein translation. However, in spite of the great potency to kill tumor cells, gelonin lacks ability to internalize tumor cells and furthermore, cannot distinguish between tumor and normal cells. To address this challenge, we genetically engineered gelonin fusion proteins with varied numbers of F3 peptide possessing homing ability to various cancer cells and angiogenic blood vessels. The <I>E. coli</I> produced F3-gelonin fusion proteins possessed equipotent activity to inhibit protein translation in cell-free protein translation systems to unmodified gelonin; however, they displayed higher cell uptake that led to significantly augmented cytotoxicity. Compared with gelonin fusion with one F3 peptide (F3-Gel), tandem-multimeric F3-gelonins showed even greater cell internalization and tumor cell killing ability. Moreover, when tested against LNCaP <I>s.c.</I> xenograft tumor bearing mice, more significant tumor growth inhibition was observed from the mice treated with tandem-multimeric F3-gelonins. Overall, this research demonstrated the potential of utilizing tandem multimeric F3-modified gelonin as highly effective anticancer agents to overcome the limitations of current chemotherapeutic drugs.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

종로 문학공간의 데이터베이스 구축방안

이은숙(Eunsook Lee),김일림(Il-Rim Kim),정희선(Heesun Cheong) 한국문화역사지리학회 2007 문화 역사 지리 Vol.19 No.2

  본 연구의 목적은 종로지역의 문화컨텐츠 개발로서 문학공간을 발굴하고, 그것을 데이터베이스로 구축하는데 있다. 종로지역을 사례지역으로 선정한 이유는 이 지역이 조선시대에 북악산, 인왕산, 낙산의 자연능선을 따라 만들어진 도성 안 부분으로서 근ㆍ현대를 거치면서 많은 문인들의 흔적이 남아있는 공간이며, 다양한 문학 작품 속에 생생하게 묘사되었기 때문이다. 본 연구의 결과는 종로지역 작품의 배경이 된 소설과 시로부터 작품 중심 문학공간, 작가 중심 문학공간, 가시적 문학공간을 발굴하여 데이터베이스를 구축하였다. 그 선정기준은 다음과 같다. 첫째, 중ㆍ고등학교 국어와 문학 교재에 포함된 작가들과 그들의 작품, 둘째, 대학교양 국어 교재 속의 작품, 셋째, 교육부와 신문 필독도서에 포함된 작가들과 그들의 작품, 넷째, 문학사조와 관련된 주요 작가들과 그들의 작품을 포함하였다. 결국 본 연구목적은 종로지역의 문학공간을 데이터베이스로 구축한 독창적인 실험모델로서 다른 지역에 선행모델을 제시해주고자 한다.   This research aims to establish databases of information on literary space and to develop literary space as a case study of Jongno area in Seoul. In this research, databases of information on literary space, including literary works, memorials and writers related to Jongno area are constructed in order to establish providing information on Jongno literary space. The criterion of this study are as follows. first, literary works and writers including the national language of middle, highschool, and literary textbooks, second, literary works on national language of college educations, third, literary works and writers including a must book by Ministry of Education and newspapers, forth, literary works and the principal writers related to the tend of literature are included. This study suggests a pilot model established databases of information on literary space of Jongno area in Seoul.

Prolyl isomerase Pin 1 regulates the osteogenic activity of Osterix

( Sung Ho Lee ),( Hyung Min Jeong ),( Younho Han ),( Heesun Cheong ),( Bok Yun Kang ),( Kwang Youl Lee ) 전남대학교 약품개발연구소 2015 약품개발연구지 Vol.24 No.-

Osterix is an essential transcription factor for osteoblast differentiation and bone formation. The mechanism of regulation of Osterix by post-translational modification remains unknown. Peptidyl-prolyl isomerase 1 (Pin1) catalyzes the isomerization of pSer/Thr-Pro bonds and induces a conformational change in its substrates. subsequently regulating diverse cellular processes. In this study. we demonstrated that Pin1 interacts with Osterix and influences its protein stability and transcriptional activity. This regulation is likely due to the suppression of poly-ubiquitination-mediated proteasomal degradation of Osterix. Collectively, our data demonstrate that Pin1 is a novel regulator of Osterix and may play an essential role in the regulation of osteogenic differentiation.

Investigation of early and advanced stages in ovarian cancer using human plasma by differential scanning calorimetry and mass spectrometry

Nam Ah Kim,Jing Hui Jin,Kyung-Hee Kim,Dae Gon Lim,Heesun Cheong,Yun Hwan Kim,Woong Ju,SEUNG-CHEOLKIM,Seong Hoon Jeong 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.5

Ovarian cancer is recognized with high mortalitydue to asymptomatic nature of the disease and difficultiesin diagnosing early stage of the cancer. The presentstudy evaluates the use of differential scanning calorimetry(DSC) in differentiating the severity of ovarian cancer fromhealthy women. 47 diseased women were subdivided intofour stages with respect to clinical relevance and severity. Stages I–II were regarded as early stages and stages III–IVwere regarded as advanced stages. The two average transitiontemperatures (Tm) increased with disease severityfrom 64.84 and 70.32 C (healthy) to 68.46 and 75.24 C(stage IV), respectively. Tm were increased depending onclinical groups. In addition, the change in heat capacity wasalso dependent on the disease severity. To further supportand investigate the nature of the proposed interactions,matrix assisted laser desorption/ionization time-of-flightmass spectrometry (MALDI-TOF MS) analysis isemployed. The results suggest the differences in peptideexpression between early and advanced stage of ovariancancer, affected abundant proteins in plasma. The combinedDSC and MS approach was supportive in identifyinga unique signature of ovarian cancer stages, anddemonstrates the potential of DSC as a complementarydiagnostic tool in the evaluation of early stage ovariancancer.