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.

Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

Synthesis of Sr Doped HoCrO3 Solid Solution Systems and Their Electrical Properties

PARK, SUNG HO,Kwon, Tae Yun 한국공업화학회 2000 Journal of Industrial and Engineering Chemistry Vol.6 No.4

Ho_(1-x)SrxCrO₃ systems, with perovskite structures, were synthesized for x=0, 0.05, 0.1, 0.2 at 1300 ℃ under atmospheric pressure. The results of X-ray analysis reveals that these prepared systems forms orthorhombic structures. Also, the HoCrO₃ systems which were doped with Sr cations on the site of Ho cations, exhibited a linear increase in their cell volume. It was found that the lattice parameter and reduced volume increased as the doping level of Sr^(2+) increased. From the measurements of D.C conductivity, the activation energy obtained from the conductivity dependence on temperature was 0.18 eV. The conduction mechanism would appear to be the hopping model of electron conduction.

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

Yun Ho Jo,Hwan Lee,Myeong Hwan Oh,Gyeong Hee Lee,You Jin Lee,Ji Sun Lee,Min Jung Kim,Won Yong Kim,Jin Seong Kim,Dae Seok Yoo,Sang Won Cho,Seon Woo Cha,Mi Kyung Pyo 한국영양학회 2020 Nutrition Research and Practice Vol.14 No.4

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson"s trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

Restoration Project of Heumgyeonggak-nu (欽敬閣漏) in the King Sejong Era

Sang Hyuk Kim,Yong-Hyun Yun2,Byeong-Hee Mihn,Seon Young Ham,Kyung Ha Lee,Dae-Sik Yoon,Go-Eun Choi,Ho-Chul Ki,Myung-Kyoon Yoon 한국천문학회 2017 天文學會報 Vol.42 No.2

“Home Is Not a Little Thing”: Reconceptualizing the Notion of Home in Toni Morrison’s Paradise

( Yun¸ Sung-ho ) 동국대학교 영어권문화연구소 2008 영어권문화연구 Vol.1 No.-

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

Lee, Sang-sun,Choe, Yun-Jeong,Lee, Hyein,Lee, Sun-Young,Kim, Ho-Shik THE KOREAN SOCIETY OF TOXICOGENOMICS AND TOXICOPRP 2018 MOLECULAR AND CELLULAR TOXICOLOGY Vol. No.

제주도 지하수 질산염 농도의 시·공간적 변화 특성: 장기(1993-2015) 모니터링 자료의 평가

김호림(Ho-Rim Kim),오준섭(Junseop Oh),도현권(Hyun-Kwon Do),이경진(Kyung-Jin Lee),현익현(Ik-Hyun Hyun),오상실(Sang-Sil Oh),감상규(Sang-Kyu Kam),윤성택(Seong-Taek Yun) 대한자원환경지질학회 2018 자원환경지질 Vol.51 No.1

1993년부터 2015년까지 관측된 제주도 지하수 장기모니터링 관측정(N = 4,835)에서 수집된 지하수 수질자료(N = 21,568)를 기반으로 질산성질소의 시공간적 변동 특성을 평가하였다. 제주도 지하수의 질산성질소 농도의 중앙값은 2.5 mg/L로서 다른 국가나 대륙의 조사 결과에 비해 다소 높거나 유사한 것으로 나타났다. 또한 지하수 용도, 행정구역 및 고도 별로 유의한 차이를 보였다. 특히, 산간 지역에 비해 저지대 해안가에 위치한 농업 및 주거지역에서 농도가 높음을 확인하였다. Mann-Kendall 및 Sen’s slope 분석을 활용한 질산성질소 농도의 추세 분석 결과, 하류 저지 대에 비해 중산간지역에서의 질산성질소 농도 증가 경향이 뚜렷하였다. 제주도 내 토지 피복의 시계열 변화 특성과 결부 지어 보면, 중산간지역의 오염 증가 추세는 농업지역의 확장 등 인위적 활동 증가에 기인한 결과로 판단된다. 반면,기지정된 지하수자원특별관리구역에서는 전반적으로 질산성질소 농도의 감소 경향이 나타났는데, 이는 지하수 관리 측면에서 수질관리를 위한 적극적인 정책이 유효함을 시사한다. 본 연구에서는 제주도 지하수의 질산성질소 오염관리를 위한 적정 방안을 제안한다. The spatio-temporal variations of nitrate concentrations in groundwater of Jeju Island were evaluated by an analysis of time series groundwater quality data (N = 21,568) that were collected from regional groundwater monitoring (number of wells = 4,835) for up to 20 years between 1993 and 2015. The median concentration of NO 3 -N is 2.5 mg/L, which is slightly higher than those reported from regional surveys in other countries. Nitrate concentrations of groundwater in wells tend to significantly vary according to different water usage (of the well), administrative districts, and topographic elevations: nitrate level is higher in low-lying agricultural and residential areas than those in high mountainous areas. The Mann-Kendall trend test and Sen’s slope analysis show that nitrate concentration in mid-mountainous areas tends to increase, possibly due to the expansion of agricultural areas toward highland. On the other hand, nitrate concentrations in the Specially Designated Groundwater Quality Protection Zones show the temporally decreasing trend, which implies the efficiency of groundwater management actions in Jeju. Proper measures for sustainable groundwater quality management are suggested in this study.

Phosphodiesterase inhibitor improves renal tubulointerstitial Hypoxia of the Diabetic rat Kidney

( Hui Kyoung Sun ),( Yun Mi Lee ),( Kum Hyun Han ),( Han Seong Kim ),( Seon Ho Ahn ),( Sang Youb Han ) 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.2

Background/Aims: Renal hypoxia is involved in the pathogenesis of diabetic nephropathy. Pentoxifyllin (PTX), a nonselective phosphodiesterase inhibitor, is used to attenuate peripheral vascular diseases. To determine whether PTX can improve renal hypoxia, we investigated its effect in the streptozocin (STZ)-induced diabetic kidney. Methods: PTX (40 mg/kg, PO) was administered to STZ-induced diabetic rats for 8 weeks. To determine tissue hypoxia, we examined hypoxic inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1) levels. We also tested the effect of PTX on HIF-1α in renal tubule cells. Results: PTX reduced the increased protein creatinine ratio in diabetic rats at 8 weeks. HIF-1α, VEGF, and GLUT-1 mRNA expression increased significantly, and the expression of HO-1 also tended to increase in diabetic rats. PTX significantly decreased mRNA expression of HIF-1α and VEGF at 4 and 8 weeks, and decreased HO-1 and GLUT-1 at 4 weeks. The expression of HIF-1α protein was significantly increased at 4 and 8 weeks in tubules in the diabetic rat kidney. PTX tended to decrease HIF-1α protein expression at 8 weeks. To examine whether PTX had a direct effect on renal tubules, normal rat kidney cells were stimulated with CoCl2 (100 μM), which enhanced HIF-1α mRNA and protein levels under low glucose conditions (5.5 mM). Their expressions were similar even after high glucose (30 mM) treatment. PTX had no effect on HIF-1α expression. Conclusions: PTX attenuates tubular hypoxia in the diabetic kidney.