Unique Unfoldase/Aggregase Activity of a Molecular Chaperone Hsp33 in its Holding-Inactive State

Jo, Ku-Sung,Kim, Ji-Hun,Ryu, Kyoung-Seok,Kang, Joo-Seong,Wang, Chae-Yeon,Lee, Yoo-Sup,Seo, Min-Duk,Lee, Young-Ho,Won, Hyung-Sik Academic Press 2019 Journal of molecular biology Vol.431 No.7

<P><B>Abstract</B></P> <P>The various chaperone activities of heat shock proteins contribute to ensuring cellular proteostasis. Here, we demonstrate the non-canonical unfoldase activity as an inherent functionality of the prokaryotic molecular chaperone, Hsp33. Hsp33 was originally identified as a holding chaperone that is post-translationally activated by oxidation. However, in this study, we verified that the holding-inactive reduced form of Hsp33 (<SUP>R</SUP>Hsp33) strongly bound to the translational elongation factor, EF-Tu. This interaction was critically mediated by the redox-switch domain of <SUP>R</SUP>Hsp33 and the guanine nucleotide-binding domain of EF-Tu. The bound <SUP>R</SUP>Hsp33, without undergoing any conformational change, catalyzed the EF-Tu aggregation by evoking the aberrant folding of EF-Tu to expose hydrophobic surfaces. Consequently, the oligomers/aggregates of EF-Tu, but not its functional monomeric form, were highly susceptible to proteolytic degradation by Lon protease. These findings present a unique example of an ATP-independent molecular chaperone with distinctive dual functions—as an unfoldase/aggregase and as a holding chaperone—depending on the redox status. It is also suggested that the unusual unfoldase/aggregase activity of <SUP>R</SUP>Hsp33 can contribute to cellular proteostasis by dysregulating EF-Tu under heat-stressed conditions.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Hsp33 was originally identified as an oxidation-dependent holding chaperone. </LI> <LI> Holding-inactive reduced form of Hsp33 (<SUP>R</SUP>Hsp33) specifically interacted with EF-Tu. </LI> <LI> <SUP>R</SUP>Hsp33-bound EF-Tu underwent an unfolding, leading to oligomerization/aggregation. </LI> <LI> EF-Tu oligomers/aggregates became susceptible to degradation by Lon protease. </LI> <LI> Aggregase activity of <SUP>R</SUP>Hsp33 can contribute to proteostasis by dysregulating EF-Tu. </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Expression of smooth muscle specific myosin by urinary bladder smooth muscle cells in vitro

Gon-sup Kim,Jong-su Kim,Ze Wang,Samuel,K,Chacko 대한수의학회 1997 대한수의학회 학술대회발표집 Vol.1997 No.-

Development of Random Forest Algorithm Based Prediction Model of Alzheimer’s Disease Using Neurodegeneration Pattern

JeeYoung Kim,Minho Lee,Min Kyoung Lee,Sheng-Min Wang,Nak-Young Kim,Dong Woo Kang,Yoo Hyun Um,Hae-Ran Na,Young Sup Woo,Chang Uk Lee,Won-Myong Bahk,Donghyeon Kim,Hyun Kook Lim 대한신경정신의학회 2021 PSYCHIATRY INVESTIGATION Vol.18 No.1

Objective Alzheimer’s disease (AD) is the most common type of dementia and the prevalence rapidly increased as the elderly population increased worldwide. In the contemporary model of AD, it is regarded as a disease continuum involving preclinical stage to severe dementia. For accurate diagnosis and disease monitoring, objective index reflecting structural change of brain is needed to correctly assess a patient’s severity of neurodegeneration independent from the patient’s clinical symptoms. The main aim of this paper is to develop a random forest (RF) algorithm-based prediction model of AD using structural magnetic resonance imaging (MRI). Methods We evaluated diagnostic accuracy and performance of our RF based prediction model using newly developed brain segmentation method compared with the Freesurfer’s which is a commonly used segmentation software. Results Our RF model showed high diagnostic accuracy for differentiating healthy controls from AD and mild cognitive impairment (MCI) using structural MRI, patient characteristics, and cognitive function (HC vs. AD 93.5%, AUC 0.99; HC vs. MCI 80.8%, AUC 0.88). Moreover, segmentation processing time of our algorithm (<5 minutes) was much shorter than of Freesurfer’s (6-8 hours). Conclusion Our RF model might be an effective automatic brain segmentation tool which can be easily applied in real clinical practice.

Structure-Activity Relationship and Evaluation of Phenethylamine and Tryptamine Derivatives for Affinity towards 5-Hydroxytryptamine Type 2A Receptor

( Shujie Wang ),( Anlin Zhu ),( Suresh Paudel ),( Choon-gon Jang ),( Yong Sup Lee ),( Kyeong-man Kim ) 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.2

Among 14 subtypes of serotonin receptors (5-HTRs), 5-HT_2AR plays important roles in drug addiction and various psychiatric disorders. Agonists for 5-HT_2AR have been classified into three structural groups: phenethylamines, tryptamines, and ergolines. In this study, the structure-activity relationship (SAR) of phenethylamine and tryptamine derivatives for binding 5-HT_2AR was determined. In addition, functional and regulatory evaluation of selected compounds was conducted for extracellular signal-regulated kinases (ERKs) and receptor endocytosis. SAR studies showed that phenethylamines possessed higher affinity to 5-HT_2AR than tryptamines. In phenethylamines, two phenyl groups were attached to the carbon and nitrogen (R³) atoms of ethylamine, the backbone of phenethylamines. Alkyl or halogen groups on the phenyl ring attached to the β carbon exerted positive effects on the binding affinity when they were at para positions. Oxygen-containing groups attached to R³ exerted mixed influences depending on the position of their attachment. In tryptamine derivatives, tryptamine group was attached to the β carbon of ethylamine, and ally groups were attached to the nitrogen atom. Oxygen-containing substituents on large ring and alkyl substituents on the small ring of tryptamine groups exerted positive and negative influence on the affinity for 5-HT_2AR, respectively. Ally groups attached to the nitrogen atom of ethylamine exerted negative influences. Functional and regulatory activities of the tested compounds correlated with their affinity for 5-HT_2AR, suggesting their agonistic nature. In conclusion, this study provides information for designing novel ligands for 5-HT_2AR, which can be used to control psychiatric disorders and drug abuse.

Differentially expressed proteins in the liver of Gulo-/- mice following treatments with Helicobacter pylori and diethylnitrosamine

Gon-Sup Kim , Arulkumar Nagappan, Hyeon-Soo Park, Kwang-Il Park, Jin-A Kim, Gyeong-Eun Hong, Silvia Yumnam, Eun-Hee Kim, Won-Sup Lee, Wang-Jae Lee, Myung-Je Cho, Woo-Kon Lee, Chung-Kil Won 충북대학교 동물의학연구소 2013 Journal of Biomedical and Translational Research Vol.14 No.2

Vitamin C (ascorbic acid) is an essential nutrient of most living tissues. We established a strain of Gulo-/- mice with known deficiency, in which vitamin C intake can be controlled by diet, like humans, and investigated the differentially expressed proteins following treatments with Helicobacter pylori and diethylnitrosamine (DENA) in the liver of Gulo-/- mice using a proteomic approach. Expression of p53, 14-3-3ε and 14-3-3δ in Gulo-/- mice liver tissue was analyzed by immunohistochemistry. 2-DE maps constructed from Gulo-/- mice liver and differentially expressed proteins in liver tissue were identified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF/MS). In Gulo-/- mice after H. Pylori infection, followed by treatment with DENA, no differences in p53, 14-3-3ε and 14-3-3δ were observed by immunohistochemistry. Proteome analyses using MALDI-TOF/MS resulted in successful identification of 12 proteins (nine proteins were up-regulated and three were down-regulated). Specifically, peroxiredoxin-6 and Alpha-1-antitrypsin 1-4 were up-regulated in liver after H. Pylori infection followed by treatment with DENA. These results indicated that oral supplementation with vitamin C led to rescue of Gulo-/- mice from vitamin deficiency, and protected the liver from H.pylori infection and/or DENA effect, and vitamin C also protected the liver against oxidative stress

Can Atypical Antipsychotic Augmentation Reduce Subsequent Treatment Failure More Effectively Among Depressed Patients with a Higher Degree of Treatment Resistance? A Meta-Analysis of Randomized Controlled Trials

Wang, Hee Ryung,Woo, Young Sup,Ahn, Hyeong Sik,Ahn, Il Min,Kim, Hyun Jung,Bahk, Won-Myong Oxford University Press 2015 International Journal of Neuropsychopharmacology Vol.18 No.8

<P><B>Background:</B></P><P>Atypical antipsychotic augmentation was demonstrated to be efficacious in treatment-resistant depression (TRD) in previous meta-analyses. We investigate whether there are differences in the effect size of atypical antipsychotic augmentation in major depressive disorder according to the degree of treatment resistance.</P><P><B>Methods:</B></P><P>A comprehensive search of four databases identified 11 randomized controlled trials. The 11 trials, which included 3 341 participants, were pooled using a random-effects meta-analysis.</P><P><B>Results:</B></P><P>Atypical antipsychotic augmentation of antidepressant therapy showed superior efficacy compared to antidepressant monotherapy in TRD in terms of both response and remission rates (response, risk ratio [RR] = 1.38, 95% confidence interval [CI] = 1.25 to 1.53; remission, RR = 1.62, 95% CI = 1.42 to 1.85). In addition, regarding response rates in the TRD trials, atypical antipsychotic augmentation exhibited significantly different effect sizes according to the degree of treatment resistance (TRD 1: RR = 1.24; TRD 2: RR = 1.37; TRD 2–4: RR = 1.58). In non-TRD trials, atypical antipsychotic augmentation failed to show superior efficacy over antidepressant monotherapy in terms of remission rates (RR = 0.89; 95% CI = 0.69 to 1.14). Atypical antipsychotic augmentation of antidepressant therapy exhibits greater effect size in patients with a higher degree of treatment resistance.</P><P><B>Conclusions:</B></P><P>This finding strengthens the rationale for considering atypical antipsychotic augmentation among depressed patients with multiple previous treatment failures in clinical practice. The efficacy of atypical antipsychotic augmentation for non-TRD seems to be different from that for TRD and, thus, further studies of non-TRD populations are needed.</P>

Polyvinylidene Fluoride Electret의 熱刺激電流特性

金旺坤,李莊燮 서울産業大學校 1986 논문집 Vol.24 No.1

室溫이상의 高溫領域에서 未延伸PVDF(α-PVDF)와 延伸PVDF(β-PVDF)의 熱刺激電(TSC)를 관측하였다. 그 결과 α-PVDF에서는 3개의 피크 P₁, P₂, P₃가 관측되었으 β-PVDF에서는 2개의 피크 P`₂, P`₃가 관측되었다. 이 피크중 P`₁, P`₂, P`₂피크는 모 結晶과 非晶質의 경계면에 트랩된 空間電荷의 脫트랩에 의한 피크이며 P₃ 과 P₃` 피크는 晶융해로 인하여 結晶내에 트랩된 空間電荷가 脫트랩되어 나타나는 피크임이 결론되었다. 또 部分加熱法에 의한 測定結果 α-PVDF는 0.9eV와 1.3 eV에 해당하는 두 개의 불연속인 트랩이 존재하며 이 시료 내에서의 P₁, P₂ 피크 특성은 이들의 複合緩和特性에 기인하 것을 추정되었다. Thermal cleaning方法에 의해 위의 複合緩和特性을 單一緩和特性으로 분해하여 이것들과 單一트랩모델에 관한 TCS 理論式과를 Curve Fitting한 결과로 부터 피크는 0.95 eV, P₂피이크는 1.3eV에 잘 일치하였다. Investigation on the characteristics of thermally stimulated current of yvinylidene fluoride (noted as PVDF) were carried out at the range of higher perature than the ambient one to the specimen of the unstretched PVDF (called as α-PVDF) and the stretched PVDF(called as β-PVDF) respectively. As the observation resulted, several peak were identified such as P₁, P₂ and for α-PVDF and P₂`and P₃` for β-PVDF and that was concluded apparently that the peaks of P₁, P₂and P₂` were orginated from the detrapped charge at the interface of crystal and amorphous phases, while the origins of the peaks to P₃and P₃` were attributed to the space charge trapped in crystallized region which in turn, was liberated in the course of crystal melting process. Furthermore two kind of isolated trap levels such as 0.9 eV and 1.3 eV were identified on α-PVDF by means of partial heating method, and that the behaviors of P₁and P₂peaks were interpreted as the complex relaxation process of the trapped charges from those two traps. Finally those peaks were separated by means of thermal cleaning method to the respective single relaxation process in order to adapt the technique of curve fitting method and it was confirmed from the results that the trap depths were also 0.95 eV for P₁peak and 1.3 eV for P₂peak.

CHARACTERIZATION OF THE PUTATIVE E2 ENVELOPE GLYCOPROTEINS OF HEPATITIS C VIRUS EXPRESSED IN STABLY TRANSFORMED CHINESE HAMSTER OVARY CELL

Wang Shick Ryu,Deog Young Choi,Hong Sup So,Jae Young Yang,Chun Hyung Kim,Ki Wha Kim,Joong Myung Cho 생화학분자생물학회 1994 생화학분자생물학회 추계학술발표논문집 Vol.- No.-

A Study on the Problems and Countermeasures of Environmental Pollution Caused by China's Rural Development - Enlightened from the Semaul movement in Korea -

Wang Young Le,Fan Ping,Kim, Dong-Baek,So, Kwang-Sup 한국자치행정학회 2009 한국자치행정학보 Vol.23 No.1

중국은 개혁개방 이래 농촌지역 경제의 급속 성장에 따라 농촌의 환경문제가 관심의 대상이 되고 있다. 특히 심각한 환경오염은 농촌의 생태, 생산 및 생활 안전에 대해 큰 영향을 미쳐 농촌의 경제와 사회적인 지속 가능한 개발에 대해 매우 중요한 억제요인이 되었다. 중국 농촌 환경오염의 원인을 향진기업(乡镇企业)의 오염 문제, 농업 비점 오염 문제, 대규모 축산업 오염 문제, 생활 오수 및 폐기물의 오염 문제 등을 중심으로 분석하였다. 중국 농촌 환경 문제를 해결하려면 한국의 새마을운동을 거울삼아야 한다. 새마을 운동으로 인해 농촌의 생활환경이 몰라보게 달라졌고 농촌의 가난이 물러가기 시작했으며 국민들의 사고와 행동이 변화되는 조짐을 보였다. 한국의 산림녹화정책의 효과를 중심으로 중국의 환경오염 방지 대책에 대해 살펴봤다. 중국에서 농촌 환경 오염문제를 해결하려면 우선 향진기업의 오염 통제를 강화하고 기업은 합리적인 분배해야 하고, 농업 비점오염의 통제를 강화하고, 생태 농업을 적극적으로 개발해야 하고, 과학적이고 합리적인 축산업 시스템을 구축하고, 가축 배출물에 대한 종합 처리를 위해 간편하고 효율적인 처리기술을 보급하여야 한다. 한국의 새마을 운동과 산림녹화계획 및 친환경 농업 등 성공한 경험으로부터도 좋은 교훈을 얻을 수 있다는 점을 비교행정론적으로 분석하였다. Along with the rural industrialization and the urbanized scale's unceasing expansion, along with the municipal pollution to the countryside pollution spread, pollution along with the east to the west shifts, along with the population activity frequent and rural economic development speed's quickening, China rural environment pollution assumes the trend of development. The countryside clean river sand the lake are getting fewer and fewer; The countryside soil erosion and the desertification area are expanding unceasingly; Countryside source of pollution with difficulty active control; The countryside beautiful scenery and the clear air are leaving us to go slowly. The rural environment protection's pressure is getting bigger and bigger. the main reasons Cause China rural environment pollution are the following five points: 1)The agricultural production creates pollution. 2) Infrastructure backwardness produces life pollution. 3)The rural enterprise layout is improper and the lack of insufficiently control produces industrial pollution. 4) Water quality of the water source area dropping is unable to withstand the load. 5) The mineral resource development, blind chop or the unreasonable non-farming resource development are important factors causing environmental pollution and ecological degradation. In the hope of China's rural ecological environment management, experiences of South Korea on how to pay attention to the rural ecological environment construction in the new rural areas building are introduced, the present situation and causes of the environment pollution in the rural area are expounded, and a countermeasure to the problem is put forward, which is to follow the way of sustainable development, to establish good farm biological environment and to uphold the coordinational development of the rural environment and the economy.

π AND OTHER FORMULAE IMPLIED BY HYPERGEOMETRIC SUMMATION THEOREMS

KIM, YONG SUP,RATHIE, ARJUN KUMAR,WANG, XIAOXIA Korean Mathematical Society 2015 대한수학회논문집 Vol.30 No.3

By employing certain extended classical summation theorems, several surprising ${\pi}$ and other formulae are displayed.