PGA2-induced expression of HO-1 is mediated by transcriptional upregulation of Nrf2

Sang-sun Lee,Yun-Jeong Choe,Hyein Lee,Sun-Young Lee,Ho-Shik Kim 대한독성 유전단백체 학회 2019 Molecular & cellular toxicology Vol.15 No.2

Backgrounds: Prostaglandin (PG) A2 reportedly stimulated expression of heme oxygenase (HO)-1 at the level of transcription via the activation of p38MAPK. Details of the mechanism, however, have not been provided, and this includes identification of the transcription factors responsible for PGA2-induced HO-1 expression. Herein is described an analysis of the role of nuclear factor erythroid 2 related factor 2 (Nrf2) and how PGA2 increases the activity of Nrf2 during PGA2-induced HO-1 expression. Methods: Expressions of HO-1 and Nrf2 were analyzed at the levels of both mRNA and protein. Nrf2 siRNA, SB203580, an inhibitor of p38MAPK, and scavengers of reactive oxygen species (ROS) were used to identify the effects of Nrf2, p38MAPK and ROS on PGA2-induced HO-1 expression. Results: Although SB203580 suppressed PGA2-induced HO-1 expression, genetic activation of p38MAPK could not stimulate the transcription of HO-1. Cycloheximide (CHX), an inhibitor of protein translation, almost completely prevented PGA2-induced increase of HO-1 transcription, but it did not prevent the phosphorylation of p38MAPK, which suggests that both de novo protein synthesis and p38MAPK activity are required to induce the transcription of HO-1 in response to PGA2 treatment. In addition, PGA2 increased the level of both Nrf2 mRNA and protein in a dose-dependent manner. Knockdown of Nrf2 using small interfering RNA (siRNA) suppressed PGA2-induced HO-1 expression. The PGA2-induced transcription of Nrf2 was prevented by ROS scavengers such as n-acetyl-l-cysteine and tempol but not CHX. Furthermore, siRNA against p38MAPK did not change the level of nuclear Nrf2 protein. Conclusion: These findings suggest that PGA2 induces HO-1 transcription via an increase in Nrf2 protein, the transcription of which is initiated by an accumulation of ROS that is independent of the p38MAPK activation pathway.

Protective Effect of Heme Oxygenase-1 on High Glucose-Induced Pancreatic β-Cell Injury

Lee, Eun-Mi,Lee, Young-Eun,Lee, Esder,Ryu, Gyeong Ryul,Ko, Seung-Hyun,Moon, Sung-Dae,Song, Ki-Ho,Ahn, Yu-Bae Korean Diabetes Association 2011 Diabetes and Metabolism Journal Vol.35 No.5

<P><B>Background</B></P><P>Glucose toxicity that is caused by chronic exposure to a high glucose concentration leads to islet dysfunction and induces apoptosis in pancreatic β-cells. Heme oxygenase-1 (HO-1) has been identified as an anti-apoptotic and cytoprotective gene. The purpose of this study is to investigate whether HO-1 up-regulation when using metalloprotophyrin (cobalt protoporphyrin, CoPP) could protect pancreatic β-cells from high glucose-induced apoptosis.</P><P><B>Methods</B></P><P>Reverse transcription-polymerase chain reaction was performed to analyze the CoPP-induced mRNA expression of HO-1. Cell viability of INS-1 cells cultured in the presence of CoPP was examined by acridine orange/propidium iodide staining. The generation of intracellular reactive oxygen species (ROS) was measured using flow cytometry. Glucose stimulated insulin secretion (GSIS) was determined following incubation with CoPP in different glucose concentrations.</P><P><B>Results</B></P><P>CoPP increased HO-1 mRNA expression in both a dose- and time-dependent manner. Overexpression of HO-1 inhibited caspase-3, and the number of dead cells in the presence of CoPP was significantly decreased when exposed to high glucose conditions (HG). CoPP also decreased the generation of intracellular ROS by 50% during 72 hours of culture with HG. However, decreased GSIS was not recovered even in the presence of CoPP.</P><P><B>Conclusion</B></P><P>Our data suggest that CoPP-induced HO-1 up-regulation results in protection from high glucose-induced apoptosis in INS-1 cells; however, glucose stimulated insulin secretion is not restored.</P>

류건휴의 『溪湖學的』과 『異學集辨』에 나타난 후기 영남학파의 ‘도통’과 ‘벽이단’ 의식

이상호(Lee Sang-ho) 한국동양철학회 2009 동양철학 Vol.0 No.32

이 논문은 19세기 초 호파계열에서 병호시비를 주도했던 류건휴의 『계호학적』과 『이학집변』을 중심으로, 후기 영남학인들의 도통과 이단에 대한 인식을 살펴보고 있다. 특히 이 두 책은 이황의 적통이 누구에게 이어졌는지를 중심으로 진행된 병호시비의 중요한 이론적 근거가 되었던 것으로, 향후 정재학파의 이론적 토대에 중요한 영향을 끼쳤다. 『계호학적』은 이황의 도통이 이상정에게 있다는 사실을 밝히기 위해 이상정의 어록과 문집 내용을 발췌하여 이황의 입장과 비교할 수 있도록 편집한 책이다. 『근사록』과 같은 편집체계를 통해 이상정의 철학이 이황과 완전하게 일치한다는 사실을 드러내려고 했던 것이다. 이에 비해 『이학집변』은 퇴계학의 정통성을 공고히 하기 위한 작업으로서의 성격을 가지고 있다. 이단에 대한 강한 비판을 통해 주자학 내에서의 퇴계학 정통성을 공고히 하려고 했던 것이다. 이와 같은 류건휴의 작업은 당시의 시대적 상황 속에서 ‘도통 확립의 필요성’과 이단 비판을 통한 ‘정학正學 보존의 노력’에 따른 것으로, 이를 통해 우리는 후기 영남학파의 인물들이 무엇을 중심으로 생각하면서 살아갔는지를 잘 알 수 있다. 정치적으로 이미 중앙으로부터 소외된 상태에서 그들 스스로의 자긍심과 자부심을 만들어 내고 있으면, 동시에 스스로 주자학적 정통에서 있음을 밝힘으로써 학문적인 우위성을 확보하려는 노력의 일환인 것이다. 더불어 기호학파로부터 받을 수 있는 조금의 의심에 대해서도 철저하게 불식시켜 나감으로써, 자신들 학문의 정통성을 드러내려고 했던 것이다. The purpose of this essay is to examine cognizance of 'taotung(道統: Legitimate Transmission of the Orthodoxy)' and heresy of late Yeungnam School, focused on Ryu, Geon-Hyu's "Gyeho-hakjeok(溪湖學的)" and "Yihak-jipbyeon(異學集辨)", which took the lead in Byungho Dispute(屛虎是非) in Ho faction of the early 19th century. Specially, for the next, these books affected theoretical foundation of Jeongjae School, become theoretical foundation of ByungHo Dispute which is gone on problem of whom the main line of descent of Lee Hwang is continued. Geyho-hakjeok is the book which we can compare to standpoint of Lee Hwang extracting contents of collection of works and quotations of Lee, Sang-Jeong by the book, to define the fact there is the main line of descent of Lee Hwang in Lee, Sang-Jeong. Through a system of edit like Keunsarok(『近思錄』), we can see that philosophy of Lee, Sang-Jeong perfectly correspond with it of Lee Hwang. In comparison, Yihak-jipbyeon has character as work for solidifying legitimate of Toegye's Philosophy. It is to solidify legitimate of Toegye's Philosophy in Zhuxi Studies through strong criticism about heresy. These works of Ryu, Geon-Hyu is caused by 'effort of preservation of Righteousness Philosophy(正學)' through 'necessity of establishing Taotung' and criticism of heresy, on this wise, we can see about what persons of Yeungnam School thought and lived. They make own self-esteem and pride in politically a shunned situation from the central government, at the same time, this is part of effort to secure scientific superiority, by defining that which is on legitimacy of Zhuxi Studies; besides, they was going to reveal legitimacy of own science, by eliminating a little suspicion from kiho School(畿湖學派).

N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway

( Daewoo Lee ),( Sung Ho Kook ),( Hyeok Ji ),( Seung Ah Lee ),( Ki Choon Choi ),( Kyung Yeol Lee ),( Jeong Chae Lee ) 생화학분자생물학회(구 한국생화학분자생물학회) 2015 BMB Reports Vol.48 No.11

There are controversial findings regarding the roles of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway on bone metabolism under oxidative stress. We investigated how Nrf2/HO-1 pathway affects osteoblast differentiation of MC3T3-E1 cells in response to hydrogen peroxide (H2O2), N-acetyl cysteine (NAC), or both. Exposing the cells to H2O2 decreased the alkaline phosphatase activity, calcium accumulation, and expression of osteoblast markers, such as osteocalcin and runt-related transcription factor-2. In contrast, H2O2 treatment increased the expression of Nrf2 and HO-1 in the cells. Treatment with hemin, a chemical HO-1 inducer, mimicked the inhibitory effect of H2O2 on osteoblast differentiation by increasing the HO-1 expression and decreasing the osteogenic marker genes. Pretreatment with NAC restored all changes induced by H2O2 to near normal levels in the cells. Collectively, our findings suggest that H2O2-mediated activation of Nrf2/HO-1 pathway negatively regulates the osteoblast differentiation, which is inhibited by NAC. [BMB Reports 2015; 48(11): 636-641]

PGA2 induces the expression of HO-1 by activating p53 in HCT116 cells

Hyein Lee,Sang-Sun Lee,Ji-Young Park,Yun-Jeong Choe,이선영,Ho-Shik Kim,H.-S. Kim 대한독성 유전단백체 학회 2017 Molecular & cellular toxicology Vol.13 No.2

Prostaglandin (PG) A2 which is a cytotoxic PG, was reported to induce the expression of heme oxygenase (HO)-1 via activation of p38MAPK to keep U2OS cells from cell cycle arrest in G2M phase. The expression of HO-1 is primarily regulated at the level of transcription. But the transcription factors that are responsible for PGA2-induced HO-1 expression were not clarified yet. Here, we report that PGA2-induced transcription of HO-1 is mediated by p53, a tumor suppressive transcription factor. In HCT116 cells, PGA2 treatment led to the phosphorylation of p53 and an increase of p21WAF1 transcription as well as the activation of HO-1 transcription. Knocking p53 down via RNA interference or inhibiting the p53’s transcriptional activity by pifithrin-α treatment led to suppression of the increase in the level of both HO-1 expression and activity of HO-1 promoter. Pretreatment of NU- 7441, a chemical inhibitor of DNA-activated protein kinase (DNA-PK), prevented both the PGA2-induced phosphorylation of p53 and an increase of HO-1 transcription. In addition, N-acetyl-l-cysteine, a scavenger of reactive oxygen species (ROS), also mimicked the effect of NU-7441 on the PGA2-induced activation of p53 and HO-1 transcription. Collectively, these results suggest that PGA2 induces the expression of HO-1 via activation of p53, which is mediated by the ROSDNA- PK pathway.

FK506이 T 림프구 사멸에서 활성산소 생성에 미치는 영향

이호균(Ho Kyun Lee),정상영(Sang Young Chung),최수진나(Soo Jin Na Choi) 대한외과학회 2009 Annals of Surgical Treatment and Research(ASRT) Vol.77 No.5

Purpose: Tacrolimus (FK506) has been widely used as an immunosuppressant in organ transplanted recipients to suppress organ rejection phenomenon. We investigated the role of oxidative stress and heme oxygense-1 by FK506 on human Jurkat T cells. Methods: The cells viability was examined by DAPI stain, enzyme activity of caspase family proteins, and western blotting for Baks, PUMA, iNOS, HO-1. Cells were cultured in the absence or presence of CoPPIX or ZnPPIX and the fluorescence intensity was analyzed using a flow cytometry. Results: Treatment with FK506 increased the generation of reactive oxygen species (ROS), including hydrogen peroxide and superoxide anion, and NO in Jurkat cells in a dose-dependent manner. Immunohistochemistry and Western blot analysis data revealed the hemoxygenase-1 (HO-1) was induced by the addition of FK506 in Jurkat cells. Induction of CoPP, HO-1 inducer, resulted in decreased intracellular H₂O₂ and NO concentrations. Instead ZnPP, an HO-1 competitive inhibitor did it reversely. In addition, ZnPP regulates iNOS protein synthesis by inhibition of HO-1. Conclusion: Increase of HO-1 expression would induce to decrease the intracellular H₂O₂ and NO concentrations. Also, HO-1 would regulate iNOS protein synthesis. Consequently, we can expect the regulation of HO-1 expression with concomitants use of FK506 to suppress organ rejection phenomenon by enhancing apoptosis.

췌장염에 의한 가성낭종내에 생긴 가성동맥류 : 1례 보고

오연희,이채경,김승현,이성우,양창현,이정호,이영현 동국대학교 경주대학 1996 東國論集 Vol.15 No.-

만성 췌장염의 합병증으로 생긴 가성동맥류는 드문질환으로, 반복적으로 다량의 출혈을 일으킬 수 있으며, 치료를 하지 않을 경우 사망율이 높기 때문에, 조기 진단과 치료가 필수적이다. 저자들은 38세 남자 환자에서 췌장염의 합병증으로 생긴 가성낭종내에서 발생한 가성동맥류 1예를 경험하였기에 보고하는 바이다. 가성 동맥류의 색혈류도플러상 낭종내에 양방향 흐름의 와류를 볼 수 있었다. Pancreatic Pseudoaneurysm within Pseudocyst from Pancreatitis: 1 Case Department of Diagnostic Radiology and Internal Medicine, College of Medicine,DongGuk University Yeon Hee OH M.D., Chae Kyeong Lee M.D., Seoung Hyeon Kim M.D., Sung Woo Lee M.D., Chang Heon Yang M.D., Jung Ho Lee M.D., Young Hyun Lee M.D. Pseudoaneurysm from pancreatitis is uncommon, but it can cause recurrent and massive hemorrhage. Because of high morbidity and mortality, early detection and treatment of the pseudoaneurysm is needed. We report a case of pseudoaneurysm within pseudocyst from pancreatitis. Color-flow Doppler sonography shows bidirectional flow and turbulent arterial flow, within anechoic mass.

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

Nd:YAG, Ho:YAG, Er:YAG 레이저 조사에 의한 상아질의 물리적 변형 및 절제(切除)역치에 관한 연구

이상호 大韓小兒齒科學會 1996 大韓小兒齒科學會誌 Vol.23 No.4

Laser application to modify healthy permanent dentin to improve microhardness and caries resistence has been previously reported but the physical modification and ablation thresholds of carious and sclerotic dentin has yet to be identified. This study determined the energy density required by modify (physical modification threshold, PMT) and remove (ablation threshold, AT) infected carious, affected and selerotic dentin compared to healthy permanent dentin. 1±0.25mm thick dentin sections(n=272) from extracted human teeth were used. Smear layer was removed 0.5M EDTA for 2 minutes. Utilizing three pulsed fiberopitc delivered contact lasers with different emission wavelengths(1.06㎛=Nd : YAG, 2.10㎛=Ho : YAG and 2.94㎛Er : YAG). The energy density(J/㎠) was incrementally increased and the resulting tissue interaction classified on a scale from 0-6. A minimum of 5 repetitions/energy density were completed. Light microscopy(10-25X) was used to verify the physical modification(scale=3) and ablation thresholds(scale=4) of the various forms of dentin and the data were analyzed by logistic regression at the 95% confidence interval. PMT and At was lower in infected dentin than in sound dentin for all lasers. PMT and AT induced by Nd : YAG>Ho : YAG>Er : YAG for all forms of dentin. Microhardness was increased in sound dentin at PMT. Morphology of crater examined by light microscopy showed Nd : YAG was safe and effective for removing carious dentin and Er : YAG was effective for removing sound dentin. The PMT and AT for YAG lasers are different as a function of dentin type which may be utilized for selective modification and removal of dentin.

소켓 용접부 결함 검사용 초음파 자동 검사 장비 개발

이정기,박문호,박기성,이재호,임성진 한국비파괴검사학회 2004 한국비파괴검사학회지 Vol.24 No.3

대구경 배관에서 소구경 배관으로 연결하는 부위 및 배관의 방향 전환을 위해 사용하는 소켓용접부는 용입불량 및 사용기간이 경과되면서 내부로부터 진전될 수 있는 균열 등의 결함을 가질 수 있다. 그러나 지금까지 적용하고 있는 비파괴검사법인 액체침투탐상과 방사선투과검사로는 내부에 존재하는 균열성 결함의 검출이 어렵다. 본 연구에서는 소켓용접부 내부의 균열성 결함 검출을 위한 초음파 검사 기법을 확립하였고, 검사를 수행할 수 있는 초음파 탐촉자를 설계 제작하였으며, 자동으로 검사할 수 있는 검사 장비와 제어용 운영 프로그램을 개발하였다. 개발된 장비는 컴퓨터를 기반으로 하고 있으며, pulser/receiver를 내장하고 100㎒ 고속 A/D board를 사용하여 초음파 탐상기 역할을 프로그램으로 구현하였으며, ISA interface type으로 4축 제어용 motion controller를 개발하여 자동 검사를 수행하는 scanner를 제어하도록 하였으며, 검사 결과는 소켓용접부 단면을 실시간 영상으로 나타내도록 되어 있다. 인공결함 ㅅ험편의 결함을 평가한 결과 결함의 깊이가 1㎜인 결함의 평가 길이는 실제 크기보다 작게 나타내고 있으며, 결함의 깊이가 증가할수록 결함의 길이가 더 크게 평가되었다. 본 연구로 개발한 장비는 원자력 발전소나 화학플랜트에 많이 널려 있는 소켓용접부 내의 용입불량, 피로 균열 등을 검출하여 객관적인 검사 결과를 제시할 수 있으므로 설비 안전 관리 및 보수 부위 결정에 기여할 수 있을 것으로 기대된다. Socket weldment used to change the flow direction of fluid may have flaws such as lack of fusion and cracks. Liquid penetrant testing or Radiography testing have been applied as NDT methods for flaw detection of the socket weldment. But it is difficult to detect the flaw inside of the socket weldment with these methods. In order to inspect the flaws inside the socket weldment, a ultrasonic testing method is established and a ultrasonic transducer and automated ultrasonic testing system are developed for the inspection. The automated ultrasonic testing system is based on the portable personal computer and operated by the program based Windows 98 or 2000. The system has a pulser/receiver, 100 ㎒ high speed A/D board, and basic functions of ultrasonic flaw detector using the program. For the automated testing, motion controller board of ISA interface type is developed to control the 4-axis scanner and a real time iC-scan image of the automated testing is displayed on the monitor. A flaws with the size of less than 1 ㎜ in depth are evaluated smaller than its actual size in the testing, but the flaws larger than 1 ㎜ appear larger than its actual size on the contrary. This tendency is shown to be increasing as the flaw size increases. A reliable and objective testing results are obtained with the developed system, so that it is expected that it can contribute to safety management and detection of repair position of pipe lines of nuclear power plants and chemical plants.