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.

Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

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).

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.

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.

플라즈마 표지소자의 제작

이상윤,라병욱,박동수,황인헌,이덕동,신영남,박성배,이동욱,박용석,박형근,손상호,권태근,채경락,정경득 慶北大學校 自然科學大學 1986 自然科學論文集 Vol.4 No.-

An Ac-type Plasma Display Panel (PDP) operating with Ne-Ar(0.1%) Penning mixture gas is fabicated. The characterics of the panel with electrodes covered with thin and thick dielectric layers are studied. The brightness of the Neon-orange light emitted by the panel measured as function of applied voltage and frequency. As an application, a graphic display system equipped with PDP showing still and moving pictures is made.

역행성 골수강내 금속정을 이용한 원위 대퇴골 간부 및 과상부 골절의 치료

이상홍,이준영,하상호,손홍문,이광철 대한골절학회 2004 대한골절학회지 Vol.17 No.2

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.