Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway

Lee, Moon Hee,Han, Min Ho,Lee, Dae-Sung,Park, Cheol,Hong, Su-Hyun,Kim, Gi-Young,Hong, Sang Hoon,Song, Kyoung Seob,Choi, Il-Whan,Cha, Hee-Jae,Choi, Yung Hyun UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.39 No.2

<P>In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and gamma H2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage. Furthermore, morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keapl) expression. Notably, these events were eliminated by transient transfection with Nrf2-specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by morin was mediated by the extracellular signal-regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK. Collectively, these results demonstrated that morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO-1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2,-induced oxidative cytotoxicity.</P>

Fluoxetine이 Schedule-Induced Polydipsia가 유발된 백서 뇌에서 Tyrosine Hydroxylase 발현에 미치는 영향

이기철,이정호,최영민,정주호,정홍경,이용민,김도형,이대환 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.2

연구목적: Fluoxetine은 serotonin을 매개하여 간접적으로 dopamine 신경전달기능을 억제한다고 추정되고 있다. 또한 운동장애에서 운동기능의 악화를 유발한다고 알려져 있다. 그러나 신경세포체에서 fluoxetine이 dopamine에 어떠한 영향을 주는지는 아직까지 확실치 않다. 저자들은 schedule-induced polydipsia를 유발시킨 백서 뇌의 흑질, 복부피개영역, 미상핵에서 tyrosine hydroxylase(TH) 발현이 저하됨을 발견하였다. 이를 통해서 fluoxetine이 백서 뇌의 dopamine 기능에 긍정적인지 혹은 부정적인지를 규명하고자 하였다. 방법: 4주간의 schedule-induced polydipsia 과정을 거친 백서에서 면역죄치화학적인 방법으로 흑질, 복부피개영역, 미상핵의 tyrosine hydroxylase 발현이 저하됨을 확인한 후, 실험동물들에게 fluoxetine 10mg/kg를 3주간 복강내 주사하였다. 실험백서들을 희생시켜 뇌 조직을 적출하여, TH 면역조직화학 염색법을 이용하여 흑질, 복부피개영역, 그리고 미상핵의 TH 면역반응세포를 관찰하고 이를 정상백서와 비교하였다. 결과: 1) 다갈증이 유발된 백서의 흑질, 복부피개영역, 미상핵에서 tyrosine hydroxylase 발현이 정상백서 보다 저하됨을 관찰하였다. 2) 3주간에 걸친 fluoxetine 투여후 흑질, 복부피개영역, 미상핵의 tyrosin hydroxylase 발현이 다시 증가하는 소견을 보였다. 결론: Fluoxetine 만성투여가 흑질, 복부피개영역 그리고 미상핵의 tyrosin hydroxylase를 증가시키는 소견을 얻었다. 이러한 결과는 임상에서 dopamine 결핍과 연관된 질환들에서 fluoxetine을 만성투여하면 운동기능을 포함한 증상들의 개선을 가져올 수도 있다고 추정된다. Objective: It has been suggested that fluoxetine inhibits the dopaminergic neurotransmission by serotonergic mediation. And also, it has been shown to inhibit synthesis of DOPA in dopamine-rich areas of the rat forebrain. These dopamine-antagonistic capacity of fluoxetine is only supported by anecdotal report that the increased amount of motor disability in patients with idiopathic Parkinson's disease after exposure to fluoxetine. However, there is still no evidence of the direct effect of fluoxetine on dopaminergic neuronal cell body in the substantia nigra, VTA, caudate & putamen. This study was designed to evaluate the effects of fluoxetine in rat brain which showed decreased numbers of dopaminergic neuronal cell body induced by schedule-induced polydipsia(SIP). Method: We incidentally found that 4 weeks of schedule-induced polydipsic rats revealed the suppression of tyrosine hydroxylase expression in the substantia nigra, VTA, caudate & putamen with the immunohistochemistric measures. After 3 weeks of intraperitoneal injection of 10mg/kg of fluoxetine to the schedule induced polydipsic rats, the tyrosine hydroxylase expression was also measured with immunohistochemistry. We compared the tyrosine hydroxylase expression among the normal control, the polydipsic rats, and the rats with fluoxetine treatment. Results: 1) By contrast with the control, the polydipsic rats revealed the evidence of decreased tyrosine hydroxylase expression in the substantia nigra, VTA, caudate & putamen. 2)After daily injection of fluoxetine for 3 weeks, the polydipsic rats showed increment of tyrosine hydroxyase expression in those areas. Conclusions: In previous studies, a great deal of results suggest that fluoxetine negatively influence the dopaminergic systems indirectly via serotonergic activation such as inhibition of dopamine synthesis or transport system. Although our results are obtained from rodents, we suggest that fluoxetine directly and positively enhance the dopamine system in the substantia nigra, VTA, caudate & putamen. The chronic adminstration of fluoxetine may be helpful to dopamine-depleted condition in clinical situations. We anticipate the replication studies of our findings and well-controlled clinical trial.

Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts

Lee, Moon Hee,Cha, Hee-Jae,Choi, Eun Ok,Han, Min Ho,Kim, Sung Ok,Kim, Gi-Young,Hong, Su Hyun,Park, Cheol,Moon, Sung-Kwon,Jeong, Soon-Jeong,Jeong, Moon-Jin,Kim, Wun-Jae,Choi, Yung Hyun Spandidos Publications 2017 International journal of molecular medicine Vol.39 No.3

<P>Natural phytochemicals of plant origin, including flavonoids, have been found to be potent antioxidants providing beneficial effects against oxidative stress-related diseases. The present study was carried out to investigate the antioxidant properties of morin, a flavonoid originally isolated from the flowering plants of the Moraceae family. Superoxide dismutase (SOD)-like activity and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) radical scavenging activity were determined. We also investigated the cytoprotective effects of morin against hydrogen peroxide (H2O2)-induced DNA damage and apoptosis in V79-4 Chinese hamster lung fibroblasts. Our results demonstrated that morin had strong scavenging effects against ABTS' radicals with enhanced SOD activity, which varied in a dose-dependent manner. Morin was found to reduce H2O2-induced intracellular reactive oxygen species generation and nuclear DNA damage, and it recovered cell viability damaged by H2O2 via inhibition of mitochondrial dysfunction-mediated apoptosis. Notably, the treatment of V79-4 cells with morin markedly enhanced the expression of heme oxygenase-1 (HO-1) but not quinone oxidoreductase-1, which was associated with the increased expression and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the downregulation of Kelch-like ECH-associated protein 1 expression. Based on our findings, we conclude that morin effectively ameliorated oxidative stress-induced DNA damage through intrinsic free radical scavenging activity and activation of the Nrf2/HO-1 pathway.</P>

동력 분산형 한국형 틸팅열차 시험 데이터 연구

이기식(Lee Gi-sik),한성호(Han Seong-ho),송용수(Song Yongsoo) 대한전기학회 2008 대한전기학회 학술대회 논문집 Vol.2008 No.11

Tilting train has been developed to increase the operational speed of the trains on conventional lines which have many curves. This train are tilted at curves to compensate for unbalanced carbody centrifugal acceleration to a greater extent than compensation produced by the track cant, so that passengers do not feel centrifugal acceleration and thus trains can run at higher speed at curves. This paper developed tilting train to evaluate train performance of TTX(korean tilting train express) with maximum operation speed 160 ㎞/h on Ho_nam Conventional Rail[1].

에탄올을 장기간 섭취한 백서에서 Acamprosate 투여가 Nitric Oxide Synthase 발현에 미치는 영향

정홍경,이기철,이정호,이승휘,이희제,정주호 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.1

에탄올이 백서의 해마에서 Neuropeptide Y 발현에 미치는 영향

정홍경,이기철,이정호,이희제,정주호,이주영 대한생물치료정신의학회 2002 생물치료정신의학 Vol.8 No.1

Bucillamine prevents cisplatin-induced ototoxicity through induction of glutathione and antioxidant genes

Kim, Se-Jin,Ho Hur, Joon,Park, Channy,Kim, Hyung-Jin,Oh, Gi-Su,Lee, Joon No,Yoo, Su-Jin,Choe, Seong-Kyu,So, Hong-Seob,Lim, David J,Moon, Sung K,Park, Raekil Nature Publishing Group 2015 Experimental and molecular medicine Vol.47 No.2

<P>Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of γ-glutamylcysteine synthetase (γ-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine <I>in vivo</I>. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.</P>

한국 정신장애의 역학 조사 연구[I] : 각 정신장애의 유병률

조맹제,함봉진,김장규,박강규,정은기,서동우,김선욱,조성진,이준영,홍진표,최용성,박종익,이동우,이기철,배재남,신정호,정인원,박종한,배안,이충경 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.4

Objectives : This study aims to estimate the prevalence of the DSM-IV psychiatric disorders in Korean population using the Korean version of Composite International Diagnostic Interview (K-CIDI). Methods : Subjects were selected by taking multi-stage, cluster samples of 7,867 adult household residents, 18 to 64 years of age, in ten catchment areas. Total 78 trained interviewers administered the K-CIDI to the selected respondents, from June 1 to November30,2001. Results : Total 6,275 respondents completed the interview. Some 33.5% of respondents reported at least one lifetime disorder, 20.6% reported at least one-year disorder, and 16.7% reported at least one-month disorder. The most common lifetime disorders were alcohol abuse/dependence (17.24%), nicotine dependence/withdrawal (11.19%), specific phobia (5.16%), and major de-pressive disorder (4.25%). The lifetime prevalence of substance abuse/dependence (0.25%) and schizophrenia (0.16%) was very low. Nicotine and alcohol use disorder showed very high male/female ratio. Mood disorder and anxiety disorder were more prevalent among female than male. Conclusion : The prevalence of psychiatric disorders was high. In comparison with other studies, remarkable differences in distributions of psychiatric disorders across the areas and times were observed.

기독교신앙이 대기업 사무직 직장인의 스트레스 과정에 미치는 완충효과

이정호,전성일,이기철,최영민 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.5

연구목적 : 기독교 신앙이 직장인의 스트레스지각과 대처 및 스트레스로 인한 우울과 불안에 미치는 완충영향들을 조사하고자 하였다. 연구방법 : 대기업 직장인 545명을 대상으로 피검자 단독 보고형 설문지를 작성하게 하였다. 설문지는 연구 목적에 대한 설명과 인구학적 조사를 포함하여, 2개의 신앙척도, 직장 스트레스척도, 일상생활 스트레스 지각척도, 대처 방식 척도, 그리고 우울과 불안 척도로 구성하였다. 결 과 : 생활 스트레스와 직장 스트레스를 지각하는 면에서는 신앙을 가지지 않은 사람들과 기독교 신앙인 사이에 차이가 없었다. 그러나 스트레스 대처에서는 기독교 신앙을 가지지 않은 사람들과 기독교 신앙인 사이에 차이가 있었다. 정서중심대처를 제외한 문제중심대처, 소망적 사고, 사회지지 추구 대처에서 모두 의미있는 차이가 있었다. 스트레스의 최종적인 결과로서 기독교 신앙 집단이 비기독교 집단에 비해 우울감정과 상태불안 그리고 기질불안 모두가 다 낮았다. 기독교 신앙을 '기독교적 사고'와 '기독교적 생활'로 구분하여 스트레스 완충기능을을 구체적으로 살펴보면, '기독교적 사고'는 직장인이 스트레스를 지각하는 데에는 아무런 영향을 주지 못하였고. 대처방식에서도 정서중심적 대처를 강화시킴으로써 오히려 스트레스에 기인하는 불안을 증가시킬 수 있음을 나타내었다. 반면에 '기독교적 생활'은 직장스트레스를 덜 지각하게 하였고, 문제중심적 대처를 강화시킴을써 결과적으로 스트레스에 의한 우울과 불안을 감소시키는 것으로 나타났다. '기독교적 생활'은 소망적 사고라는 정서중심적 대처도 강화시켰는데, 이 경우는 문제중심적 대처와 정서중심적 대처가 서로의 기능을 촉진하는 것으로 볼 수 있다. 결 론 : 기독교 신앙은 직장인의 스트레스 대처를 강화시킴으로써 스트레스로 인한 불안을 감소시켰다. Objectives : The purpose of this study was to clarify the buffering effects of Christian belief on the interactional stress process of the white-collars. Methods : The sample of this study was 545 white-collars working in the large enterprise. The questionnaire was composed of demographic data, job stress questionnaire, global assessment of recent stress, the ways of coping checklist, Beck depression inventory, stait-trait anxiety inventory, and Shepherd Scale for differentiate Christians from non Christians. Christianity was divided into 'Christian way of thinking' and 'Christian way of living' for deep survey and analysis. Results : In recognizing life stress and job stress, there was no difference between Christians and non Christian atheist. But in coping stress, there was difference between Christians and non Christians. 'Christian way of thinking' strengthened emotion focused coping, but didn't play a buffering role in reducing stress-induced depression and anxiety of the white-collars But 'Christian way of living' increased challenge-appraisal and strengthened problem focused coping as a consequence. Also, Christian way of living had a influence on hoping thought and seeking social support. As a result, Christian belief reduced depression and anxiety. Conclusion : Christian belief had a buffering effect on the interactional stress process of the white-collars of large enterprises.

윤곽선 정보와 watershed segmentation을 이용한 영역 추출

이원효,설경호,염동훈,고기영,김두영 동아대학교 정보기술연구소 2003 情報技術硏究所論文誌 Vol.11 No.1

This paper proposed a extracting method of the region for image using segmentation and edge information. First proposed algorithm extract information using canny edge detector and the image was divided by watershed segmentation. And it extract the image with edge information by merging region. Finally we compare the proposed method with levelset method. In the result proposed method not only extract the image with accurate region but also reduce operation time.