• 동의생리병리학회지
• /
• 제23권6호
• /
• pp.1305-1313
• /
• 2009

Saengjihwangeum-ja (SJHEJ) was recorded in DongEuiBoGam as being able to be used for treatment of Sogal whose concept had been applied to Diabetes Mellitus (DM). Modification of proteins by long term circulation of glucose leads to the formation of advanced glycation end product(AGE). Recent immunological studies demonstrated that ligation of AGE play an important role in the development of diabetic complications including atherosclerosis, which includes activation, adhesion, and migration of monocytes. Also, AGE and Maillard reaction product(MRP) could augment monocyte inflammatory responses via ligation of AGE receptor. In this study, the effects of SJHEJ extracts on the expression of inflammatory response-related genes such as tumor necrosis factor-$\alpha$, monocyte chemoattractant protein-1, interferon-g-inducible protein-10, and cyclooxygenase-2 in the human monocyte cell line, THP-1 cells. Reverse transcriptase-polymerase chain reaction revealed that SJHEJ had inhibitory effects on the expression of the TNF-a, MCP-1, IP-10, COX2, IL-1b genes in MRP-induced THP-1 cells. Treatment with SJHEJ had reduced reactive oxygen production in THP-1 cells stimulated by MRP. These inhibitory effects might be exerted via prevention of oxidative stress in activated monocytes. In addition, radical scavenging activity of SJHEJ was increased. These results suggest that SJHEJ has a beneficial effects for improve diabetic vascular complication.

• 생명과학회지
• /
• 제26권3호
• /
• pp.364-375
• /
• 2016

번역 후 변형 과정은 외부 자극으로부터 세포의 신속한 반응을 야기하는데 있어서 매우 효율적인 기작이다. 이 중, 유비퀴티네이션은 진핵생물 내 대표적인 번역 후 변형 과정으로서, 이러한 유비퀴티네이션에 의해 매개되는 UPS (유비퀴틴/프로테아좀 시스템)는 세포 내 다양한 단백질들의 분해과정을 통해 그들의 안정성을 조절한다. 유비퀴티네이션 과정에 참여하는 3종류의 효소 중에서, E3 효소는 분해할 대상 기질을 결정한다는 면에서 그 중요성을 가지고 있다. CRL (cullin-RING E3 ubiquitin ligase)은 E3 효소 중 가장 거대한 그룹을 형성하고 있는데, 이들은 생체 내에서 cullin, RBX1, 어댑터, 기질 수용체로 이루어진 복합체의 형태로서 그 기능을 발휘한다. 이 중, SCF 복합체로도 알려진 CRL1 복합체의 기능은 다양한 연구를 통해 광범위하게 알려져 온 반면, CRL4 복합체에 대한 연구 및 고찰은 상대적으로 미흡한 실정이다. 또한, 애기장대는 DCAF로 명명된 잠재적 기질 수용체를 총 119개 보유하고 있는데, 현재까지 이들 중 일부 기질 수용체들의 기능만이 밝혀진 상태로서, 나머지 기질 수용체들의 기능 규명은 향후 활발히 탐색되어야 할 연구분야라 할 수 있다. 본 총설에서는 식물의 CRL4 복합체의 구조 및 활성 조절을 알아보고, 각 CRL4 복합체가 관여하는 다양한 식물 내 이벤트에 관하여 최근까지 보고된 CRL4 기질 수용체들을 중심으로 그 연구 진행 사항을 업데이트하고자 한다. 이러한 접근은 각 CRL4 복합체가 기능하는 식물의 다양한 신호 전달 기작들을 보다 명확히 이해하고, 향후 전체 CRL4 복합체의 작용 네트워크를 구축하는데 있어 도움이 될 것으로 사료된다.

• The Journal of Korean Physical Therapy
• /
• 제26권3호
• /
• pp.191-195
• /
• 2014

Purpose: The purpose of this study is to investigate whether types of sensory-stimuli cues in terms of visual, auditory, and visuoauditory cues can be affected to motor sequential learning in healthy adults, using serial reaction time task. Methods: Twenty four healthy subjects participated in this study, who were randomly allocated into three groups, in terms of visual-stimuli (VS) group, auditory-stimuli (AS) group, and visuoauditory-stimuli (VAS) group. In SRT task, eight Arabic numbers were adopted as presentational stimulus, which were composed of three different types of presentational modules, in terms of visual, auditory, and visuoauditory stimuli. On an experiment, all subjects performed total 3 sessions relevant to each stimulus module with a pause of 10 minutes for training and pre-/post-tests. At the pre- and post-tests, reaction time and accuracy were calculated. Results: In reaction time, significant differences were founded in terms of between-subjects, within-subjects, and interaction effect for group ${\times}$ repeated factor. In accuracy, no significant differences were observed in between-group and interaction effect for groups ${\times}$ repeated factor. However, a significant main effect of within-subjects was observed. In addition, a significant difference was showed in comparison of differences of changes between the pre- and post-test only in the reaction time among three groups. Conclusion: This study suggest that short-term sequential motor training on one day induced behavioral modification, such as speed and accuracy of motor response. In addition, we found that motor training using visual-stimuli cue showed better effect of motor skill acquisition, compared to auditory and visuoauditory-stimuli cues.

• Nutrition Research and Practice
• /
• 제1권1호
• /
• pp.19-28
• /
• 2007

To identify regulatory molecules which play key roles in the development of obesity, we investigated the transcriptional profiles in 3T3-L1 cells at early stage of differentiation and analyzed the promoter sequences of differentially regulated genes. One hundred and sixty-one (161) genes were found to have significant changes in expression at the 2nd day following treatment with differentiation cocktail. Among them, 86 transcripts were up-regulated and 75 transcripts were down-regulated. The 161 transcripts were classified into 10 categories according to their functional roles; cytoskeleton, cell adhesion, immune, defense response, metabolism, protein modification, protein metabolism, regulation of transcription, signal transduction and transporter. To identify transcription factors likely involved in regulating these differentially expressed genes, we analyzed the promoter sequences of up- or - down regulated genes for the presence of transcription factor binding sites (TFBSs). Based on coincidence of regulatory sites, we have identified candidate transcription factors (TFs), which include those previously known to be involved in adipogenesis (CREB, OCT-1 and c-Myc). Among them, c-Myc was also identified by our microarray data. Our approach to take advantage of the resource of the human genome sequences and the results from our microarray experiments should be validated by further studies of promoter occupancy and TF perturbation.

• Toxicological Research
• /
• 제24권2호
• /
• pp.101-107
• /
• 2008

Studies on hypoxia-signaling pathways have revealed novel Fe(II) and $\alpha$-ketoglutarate-dependent dioxygenases that hydroxylate prolyl or asparaginyl residues of a transactivator, Hypoxia-Inducible $Factor-\alpha(HIF-\alpha)$ protein. The recognition of these unprecedented dioxygenases has led to open a new paradigm that the hydroxylation mediates an instant post-translational modification of a protein in response to the changes in cellular concentrations of oxygen, reducing agents, or $\alpha$-ketoglutarate. Activity of $HIF-\alpha$ is repressed by two hydroxylases. One is $HIF-\alpha$ specific prolyl-hydroxylases, referred as prolyl-hydroxylase domain(PHD). The other is $HIF-\alpha$ specific asparaginyl-hydroxylase, referred as factor-inhibiting HIF-1(FIH-1). The facts (i) that many dioxygenases commonly use molecular oxygen and reducing agents during detoxification of xenobiotics, (ii) that detoxification reaction produces radicals and reactive oxygen species, and (iii) that activities of both PHD and FIH-1 are regulated by the changes in the balance between oxygen species and reducing agents, imply the possibility that the activity of $HIF-\alpha$ can be increased during detoxification process. The importance of $HIF-\alpha$ in cancer and ischemic diseases has been emphasized since its target genes mediate various hypoxic responses including angiogenesis, erythropoiesis, glycolysis, pH balance, metastasis, invasion and cell survival. Therefore, activators of PHDs and FIH-1 can be potential anticancer drugs which could reduce the activity of HIF, whereas inhibitors, for preventing ischemic diseases. This review highlights these novel dioxygenases, PHDs and FIH-1 as specific target against not only cancers but also ischemic diseases.

• Molecules and Cells
• /
• 제38권4호
• /
• pp.327-335
• /
• 2015

Piperlongumine, a natural alkaloid isolated from the long pepper, selectively increases reactive oxygen species production and apoptotic cell death in cancer cells but not in normal cells. However, the molecular mechanism underlying piperlongumine-induced selective killing of cancer cells remains unclear. In the present study, we observed that human breast cancer MCF-7 cells are sensitive to piperlongumine-induced apoptosis relative to human MCF-10A breast epithelial cells. Interestingly, this opposing effect of piperlongumine appears to be mediated by heme oxygenase-1 (HO-1). Piperlongumine upregulated HO-1 expression through the activation of nuclear factor-erythroid-2-related factor-2 (Nrf2) signaling in both MCF-7 and MCF-10A cells. However, knockdown of HO-1 expression and pharmacological inhibition of its activity abolished the ability of piperlongumine to induce apoptosis in MCF-7 cells, whereas those promoted apoptosis in MCF-10A cells, indicating that HO-1 has anti-tumor functions in cancer cells but cytoprotective functions in normal cells. Moreover, it was found that piperlongumine-induced Nrf2 activation, HO-1 expression and cancer cell apoptosis are not dependent on the generation of reactive oxygen species. Instead, piperlongumine, which bears electrophilic ${\alpha},{\beta}$-unsaturated carbonyl groups, appears to inactivate Kelch-like ECH-associated protein-1 (Keap1) through thiol modification, thereby activating the Nrf2/HO-1 pathway and subsequently upregulating HO-1 expression, which accounts for piperlongumine-induced apoptosis in cancer cells. Taken together, these findings suggest that direct interaction of piperlongumine with Keap1 leads to the upregulation of Nrf2-mediated HO-1 expression, and HO-1 determines the differential response of breast normal cells and cancer cells to piperlongumine.

• 생명과학회지
• /
• 제28권3호
• /
• pp.376-387
• /
• 2018

식물이 접하는 다양한 환경 스트레스(고온, 저온, 냉해, 고염, 가뭄 등) 중에서 물부족(가뭄) 스트레스는 식물의 생장 및 생산성을 저해하는 가장 주요한 요인으로 보고되어 왔다. 그러므로, 물부족 스트레스에 대한 식물의 반응 기작을 명확히 이해하는 것은 물부족 스트레스 저항성이 증가된 유용 작물 개발에 적용될 수 있을 것으로 기대되며, 그 결과 작물 재배 가능 지역의 확대에 기여할 수 있을 것으로 생각된다. 식물의 물부족 스트레스 신호 과정은 크게 식물 호르몬인 앱시스산 의존적인 과정과 비의존적인 과정으로 분류되며, 각각 AREB/ABF, DREB2 전사 조절 인자가 주요한 전사 조절 인자로 참여하여 하위 단계 반응 유전자의 발현 조절에 참여한다. 이러한 AREB/ABF, DREB2 의존적인 regulon에 대한 연구를 통해 물부족 스트레스 신호 과정 중 전사 수준의 조절에 대한 규명이 활발히 이루어지고 있다. 해당 신호 과정에는 전사 수준의 조절뿐만 아니라 인산화, 유비퀴틴화와 같은 번역 후 변형 과정 및 염색질 변형에 의해 매개되는 후성유전학적 조절도 연관되어 있다. 본 총설에서는 현재까지 보고된 물부족 스트레스 신호 전달 과정을, 이와 관련되어 보고된 다양한 신호 전달 단백질들의 기능과 연계시켜 알아보고자 한다. 이러한 물부족 스트레스 신호 전달 과정에 대한 명확한 이해는 향후 유용 내건성 작물 개발을 위한 이론적 기반 구축에 도움이 될 수 있을 것이라 생각된다.

• 한국강구조학회 논문집
• /
• 제22권4호
• /
• pp.325-334
• /
• 2010

본 연구에서는 반강접 접합부 배치에 따른 구조물 거동특성을 파악하기 위하여 KBC2005 건축구조설계기준으로 비가새 5층 철골 구조물을 설계하여 모든 접합부를 완전 강접합부과 반강접 접합부로 이상화한 경우 그리고 반강접 접합부를 수직배치 및 수평배치한 경우에 대하여 푸쉬오버 구조해석을 실시하였다. 철골 보 및 기둥의 모멘트-곡률관계는 화이버모델을 이용하여 확인하였으며 반강접 접합부의 모멘트-회전각 관계는 3-매개변수 파워모델을 이용하여 나타내었다. KBC2005 등가정적횡하중을 받는 2차원 구조물에 대한 푸쉬오버 구조해석을 실시하여 지붕충변위, 밑면전단력, 접합부 요구연성도, 소성힌지 발생순서 그리고 초과강도계수, 연성계수, 반응수정계수와 같은 설계계수 등을 확인하였다. 반강접 접합부를 부분적으로 사용하면 모든 접합부에 반강접 접합부를 사용한 골조 보다 큰 강도 및 강성도를 확보 할 수 있었고 모든 접합부에 강접 접합부를 사용한 골조 보다 큰 연성능력을 확보할 수 있었다. 초과강도계수는 기준과 비슷하였지만 반응수정계수는 기준 보다 훨씬 큰 값을 보였다. TSD 접합부는 예제 구조물에서 경제성과 안전성을 확보할 수 있음을 확인할 수 있었다.

• Radiation Oncology Journal
• /
• 제13권2호
• /
• pp.113-120
• /
• 1995

Purpose : To investigate the effect of alkaloid fraction from Korean ginseng on radiation-induced DNA double strand breaks (dsb) formation and repair in murine lymphocytes Materials and Methods : We used the neutral filter elution technique to assay $^{60}Co\;{\gamma}$ ray-induced DNA double strand breaks formation and repair in C57BL/6 mouse spleen lymphocytes for evaluating the dose-response relationship in the presence of alkaloid fraction as a radioprotective agent. The lymphocytes were stimulated with Phytohemagglutinin (PHA, 2 u g/ml) to label $^3[H]-thymidine.$ Isotope-labelled lymphocytes in suspension were exposed to 100 Gy at $0^{\cdot}C$ in the alkaloid fraction-treated group and elution procedure was performed at PH 9.6. The extents of formation of radiation-induced DNA double strand breaks and repair were compared respectively via strand scission factor (SSF) and relative strand scission factor (RSSF). Results: Alkaloid fraction reduced the formation of double strand breaks with dose modification factor of 2 15, compared to control group Rejoining of DNA dsb appeared to take place via two components. The first fast component was completed within 20.4 minutes, but the second slow component was not completed until 220.2 minutes after irradiation. About $30\%$ of dsb formed by irradiation was ultimately unrejoined despite the administration of alkaloid fraction. The administration of alkaloid fraction had a great effect on the second slow component of repair; the half-time of fast component repair was not changed, but that of slow component was 621.8 minutes. Conclusion: Neutral filter elution assay Proved to be a very effective method to quantitate the extents of DNA dsb formation and its repair. By using this technique, we were able to evaluate the efficiency of alkaloid fraction from Korean ginseng as a valuable radioprotector. Alkaloid fraction can be used prophylactically to prevent or ameliorate the severe radiation damages in workers and neighbors around the atomic power plants. For more refined study, however, more advanced purification of alkaloid fraction wil be needed in the near future.

• Earthquakes and Structures
• /
• 제14권5호
• /
• pp.411-424
• /
• 2018

This study explores the inelastic behavior of systems with flexible base. The use of a single degree of freedom system (ESDOF) with equivalent ductility to represent the response of flexible base systems is discussed. Two different equations to compute equivalent ductility are proposed, one which includes the contribution of rigid body components, and other based on the overstrength of the structure. In order to asses the accuracy of ESDOF approach with the proposed equations, the behavior of a 10-story regular building with reinforced concrete (RC) moment resisting frames is studied. Local and global ductility capacity and demands are used to study the modifications introduced by base flexibility. Three soil types are considered with shear wave velocities of 70, 100 and 250 m/s. Soil-foundation stiffness is included with a set of springs on the base (impedance functions). Capacity curves of the building are computed with pushover analysis. In addition, non linear time history analysis are used to asses the ductility demands. Results show that ductility capacity of the soil-structure system including rigid body components is reduced. Base flexibility does not modify neither yield and maximum base shear. Equivalent ductility estimated with the proposed equations is fits better the results of the numerical model than the one considering elastoplastic behavior. Modification of beams ductility demand due to base flexibility are not constant within the structure. Some elements experience reduced ductility demands while other elements experience increments when flexible base is considered. Soil structure interaction produces changes in the relation between yield strength reduction factor and structure ductility demand. These changes are dependent on the spectral shape and the period of the system with fixed and flexible base.