PGA2-induced HO-1 attenuates G2M arrest by modulating GADD45α expression

Yun-Jeong Choe,고경원,Hyein Lee,이선영,Byung-Chul Kim,Ho-Shik Kim,Ho-Shik Kim 대한독성 유전단백체 학회 2015 Molecular & cellular toxicology Vol.11 No.4

Prostaglandin (PG) A2, a cyclopentenone PG, arrested the growth of U2OS cells in the G2M phase. While inducing G2M arrest, PGA2 increased the expression of heme oxygenase-1 (HO-1) at the level of transcription along with the accumulation of ROS and the activation of MAPKs including JNK, p38MAPK, and ERK1/2. Among the MAPKs, the inhibition of p38MAPK by a specific chemical inhibitor SB203580, or by RNA interference, but not JNK or ERK1/2, attenuated the PGA2-induced transcription of HO-1. Nacetylcysteine (NAC), a ROS scavenger, prevented PGA2-induced G2M arrest, p38MAPK activation and transcriptional induction of HO-1. PGA2 also stimulated GADD45α expression at the level of transcription, and the knockdown of GADD45α repressed PGA2- induced G2M arrest. Finally, the knockdown of the HO-1 protein elevated PGA2-induced GADD45α expression as well as G2M arrest. Collectively, these results suggest that PGA2 causes an increase in ROS accumulation which initiates both HO-1 transcription via p38MAPK, and G2M arrest via GADD45α transcription, and HO-1 attenuates G2M arrest by modulating the expression of GADD45α.

Nutlin-3 induces HO-1 expression by activating JNK in a transcription-independent manner of p53

CHOE, YUN-JEONG,LEE, SUN-YOUNG,KO, KYUNG WON,SHIN, SEOK JOON,KIM, HO-SHIK Spandidos Publications 2014 International journal of oncology Vol.44 No.3

A recent study reported that p53 can induce HO-1 by directly binding to the putative p53 responsive element in the HO-1 promoter. In this study, we report that nutlin-3, a small molecule antagonist of HDM2, induces the transcription of HO-1 in a transcription-independent manner of p53. Nutlin-3 induced HO-1 expression at the level of transcription in human cancer cells such as U2OS and RKO cells. This induction of HO-1 did not occur in SAOS cells in which p53 was mutated and was prevented by knocking down the p53 protein using p53 siRNA transfection, but not by PFT-alpha, an inhibitor of the transcriptional activity of p53. Accompanying HO-1 expression, nutlin-3 stimulated the accumulation of ROS and the phosphorylation of MAPKs such as JNK, p38 MAPK and ERK1/2. Nutlin-3-induced HO-1 expression was suppressed by TEMPO, a ROS scavenger, and chemical inhibitors of JNK and p38 MAPK but not ERK1/2. In addition, nutlin-3-induced phosphorylation of JNK but not p38 MAPK was inhibited by TEMPO. Notably, the levels of nutlin-3-induced ROS were correlated with the mitochondrial translocation of p53 and this induction was prevented by PFT-beta, an inhibitor of the mitochondrial translocation of p53. Consistent with the effect of the ROS scavenger and MAPK inhibitors, PFT-beta reduced HO-1 expression and the phosphorylation of JNK induced by nutlin-3. In the experiments of analyzing cell death, the knockdown of HO-1 augmented nutlin-3-induced apoptosis. Collectively, these results suggest that nutlin-3 induces HO-1 expression via the activation of both JNK which is dependent on ROS generated by p53 translocated to the mitochondria and p38 MAPK which appears to be stimulated by a ROS-independent mechanism, and this HO-1 induction may inhibit nutlin-3-induced apoptosis, constituting a negative feedback loop of p53-induced apoptosis.

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.

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.

심근 허혈-재관류 백서 모델에서 mitogen-activated protein kinase 활성화에 대한 α-lipoic acid의 효과

김연경,박은미,최준호,윤경호,유남진,이은미,김남호,정진원,김민선,박병림,오석규 圓光大學校 醫科學硏究所 2006 圓光醫科學 Vol.21 No.1

Anti-Inflammatory and Analgesic Effects of Pyeongwisan on LPS-Stimulated Murine Macrophages and Mouse Models of Acetic Acid-Induced Writhing Response and Xylene-Induced Ear Edema

Oh, You-Chang,Jeong, Yun Hee,Cho, Won-Kyung,Ha, Jeong-Ho,Gu, Min Jung,Ma, Jin Yeul MDPI 2015 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.16 No.1

<P>Pyeongwisan (PW) is an herbal medication used in traditional East Asian medicine to treat anorexia, abdominal distension, borborygmus and diarrhea caused by gastric catarrh, atony and dilatation. However, its effects on inflammation-related diseases are unknown. In this study, we investigated the biological effects of PW on lipopolysaccharide (LPS)-mediated inflammation in macrophages and on local inflammation <I>in vivo</I>. We investigated the biological effects of PW on the production of inflammatory mediators, pro-inflammatory cytokines and related products as well as the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated macrophages. Additionally, we evaluated the analgesic effect on the acetic acid-induced writhing response and the inhibitory activity on xylene-induced ear edema in mice. PW showed anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and interleukin-1β (IL-1β). In addition, PW strongly suppressed inducible nitric oxide synthase (iNOS), a NO synthesis enzyme, induced heme oxygenase-1 (HO-1) expression and inhibited NF-κB activation and MAPK phosphorylation. Also, PW suppressed TNF-α, IL-6 and IL-1β cytokine production in LPS-stimulated peritoneal macrophage cells. Furthermore, PW showed an analgesic effect on the writhing response and an inhibitory effect on mice ear edema. We demonstrated the anti-inflammatory effects and inhibitory mechanism in macrophages as well as inhibitory activity of PW <I>in vivo</I> for the first time. Our results suggest the potential value of PW as an inflammatory therapeutic agent developed from a natural substance.</P>

류마티스 관절염과 동반된 궤양성 대장염 1예

정종필,김윤아,서강석,김태현,김춘호,박정복,이광욱 朝鮮大學校 附設 醫學硏究所 2005 The Medical Journal of Chosun University Vol.30 No.2

The gastrointestinal involvement in rheumatoid arthritis may be broad and includes many causes: drug induced colitis, colitis associated with infectious agents, vasculitis in gut, autoimmune disease located in gut. Rheumatoid arthritis is a chronic multisystemic disease of unknown cause. Although a number of mixed autoimmue disease exist, there were rare reports about Ulcerative colitis with Rheumatoid arthritis associated. We report one case of Rheumatoid arthritis patient who diagnosed as Ucerative colitis by colonoscopic and histologic finding with review of literature.

韓國 會計用語의 起源과 變遷

尹根鎬,曺延煥 慶北大學校 經商大學 經濟學科 1987 慶商大學論集 Vol.15 No.-

중학교 1학년 생물영역의 사이버가정학습 콘텐츠 품질 평가

정윤영,정진수,김상호 경북대학교 과학교육연구소 2009 科學敎育硏究誌 Vol.33 No.1

이 연구에서는 전국 16개 시·도 교육청에서 운영하는 사이버가정학습 사이트에 공동으로 탑재되어진 중학교 1학년 생물영역 콘텐츠를 선정하여 학습환경, 교수설계, 학습내용, 교수학습전략, 상호작용, 지원체계, 평가, 윤리성, 저작권의 9개 영역에서 평가하였다. 평가 결과 첫째, 학습환경 평가영역에서, 콘텐츠는 학습자의 다양한 조건에서 실행이 가능하고 학습도중 다른 화면으로의 이동이 자유로워 학습자에게 편리한 학습환경으로 구성되어 있다. 둘째, 교수설계 평가영역에서, 콘텐츠는 학습목표를 명확하게 제시하고 있고 학습자의 수준을 고려하여 학습활동을 제공하고 있다. 그러나 학습안내, 선수학습, 학습평가, 학습정리의 단계는 수준별 학습이 이루어지지 않고 있다. 셋째, 학습내용 평가영역에서, 학습내용은 학교의 정규 교과 수업 내용을 바탕으로 구성되어져 있으며, 각 차시별로 제시된 학습목표에 맞는 내용으로 학습내용을 구성하고 있다. 그러나 최신 정보 및 경향으로 수정 및 보완하지 않았다. 넷째, 교수학습전략 평가영역에서, 콘텐츠는 대부분이 수동적 탐구로 이루어진 강의 중심의 자료 제시형으로 구성되어 있다. 다섯째, 상호작용 평가영역에서, 사이버가정학습의 사이트와 각 메뉴에 대한 안내를 위한 별도의 메뉴를 메인화면에 구성하고 있으나 효과적이라고 보기 어렵다. 여섯째, 지원체제 평가영역에서, 사이버가정학습의 사이트의 메인화면에 각 메뉴에 대한 안내와 학습사전, 용어사전을 제시하고 있다. 일곱째, 학습평가를 포함 한 다른 학습단계의 내용은 다른 수준의 콘텐츠를 선택 하더라도 같은 수준의 같은 내용으로 평가가 이루어지고 있다. 여덟째, 윤리성 평가영역에서, 콘텐츠는 사회적으로 지켜야 할 도리와 규범을 준수하고 있다. 아홉째, 저작권 평가영역에서 사이버가정학습 사이트를 운영하는 기관을 사이트의 메인화면 하단에 명시하고 있다. The purpose of this study was to evaluate the quality of biology contents of cyber home learning systems which provided by 16 metropolitan and provincial offices of education. The contents were evaluated by the 9 categories: needs assessment, instruction design, learning contents, teaching & learning strategy, interaction, supporting system, evaluation, ethicality and copy right. The result showed that the contents have advantage in detailed learning goal, useful learning environment, learning activities by level, and various learning parts material, but lack in evaluation method tool for personal learning by level and the latest learning material. Based on this results, it is expected that the barrier of the efficient learning contents should be searched for the complement, as well as the development high-quality educational contents and the management of cyber home learning system.

미스트 분무 및 스프링클러 관수가 단동 플라스틱 하우스에 미치는 냉각효과

강정윤,최동호,임홍성,허종철 제주대학교 산업기술연구소 2000 尖端技術硏究所論文集 Vol.11 No.2

As crops recently can be cultivated all the year in greenhouses, we need to improve the environment in which crops are able to grow in the summer. Therefore, in this study, we quantitatively got the cooling effects of 4 single span plastic greenhouses in the following ways : by spraying mist or sprinkler, or by opening the side window. and with those variables, we simultaneously did experiments at 4 greenhouses under equivalent conditions to reduce the temperature of the greenhouses in the summer. The results of the experiments are as following : 1) The temperatures of the greenhouses were effectively reduced by both spraying mist and sprinkler. 2) When the mist is intermittently sprayed. the indoor temperature has decreased by 4 degrees centigrade, meanwhile, in the greenhouse to make experiments using sprinkler, the temperature of that has been reduced by 2 degrees centigrade. Therefore, we can see the cooling effects of smaller mist in size as more effective than those of sprinkler. 3) When the greenhouse is naturally ventilated by opening the side window, we have to apply another cooling system because the indoor temperature is higher than the outdoor one.