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.

Influence of Phase Composition in TiAlSiN Hard Coatings on the Evolution of Structure and Mechanical Properties

Jeong‑Han Lee,Ik‑Hyun Oh,Jun‑Ho Jang,Ju‑Hun Kim,Sung‑Kil Hong,Hyun‑Kuk Park 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.3

The aim of this study is to investigate the structural evolution and mechanical properties of TiAlSiN coatings when processedby the arc ion plating method. To form a hard coating, Ti, Al, and Si powders were mechanically alloyed by planetary ballmilling; the powders were then densely compacted during a rapid sintering process into a ternary system coating, i.e. TiAlSi. The evolution of the structural phase from a powder to a compact material is dominated considerably by phase states suchas a supersaturated solid solution or intermetallic compounds. In the case of coating layers, the factors that determine thestructural evolution are associated with the phase stability of the nano-crystalline structure that in turn is associated withthe Ti/Al composition ratio. Motivated by this, we performed experiments to investigate the distribution of microstructures;the material’s binding energy, quantitative properties, transformation of crystal structure, and distribution of amorphous/crystalline were all recorded. In particular, the relationship between the physical and chemical properties during the coatingprocess is considered to be the dominant factor controlling the orientation and morphology of that zone (1, T, and 2). TheTiAlSiN coating layer was found to have hardness above 45 GPa and an adhesion above 100 N. In other words, understandingthe evolution and structure of TiAlSin helped us to produce a material with excellent properties that can be used as a hardcoating. Specifically, these properties were induced by a grain refinement of the nano-crystalline structure that correspondsto an increase in the silicon nitride contents.

Effect of Mechanical Alloying on the Microstructural Evolution of Al60Cr30Si10 Alloys Processed by Spark Plasma Sintering

Jeong‑Han Lee,Ik‑Hyun Oh,Jun‑Ho Jang,Ju‑Hun Kim,Sung‑Kil Hong,Hyun‑Kuk Park 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.5

In this study, Al, Cr and Si fine powders were alloyed by planetary ball milling to investigate their microstructural evolution,following their mechanical alloying behavior. The formation of Al(Cr) supersaturated solid solution by the Cr grainsembedded in Al-matrix, which contributed substitutional structure is discussed in relation to their structural evolution inaccordance with the distortion of a crystal lattice. The compacts of Al–Cr–Si alloys were prepared by rapid sintering withina short time by dense consolidation above the density of 99.9% as the formation of intermetallics, except in the case of thedistribution of single-phases induced by the Al-melting. The formation behavior of intermetallics was dominated by dependenceon the structures of the milled-powder and subsequent sintering temperature. To estimate the consolidated behaviorsof compacts, various approaches derived from TEM and XRD analysis were taken to obtain microstructural evidences ofthe inter-diffusion, following the presence of thermally stable intermetallics.

Comparative Study on interest politics in Korea and Japan : Focusing on business associations

Jeong,Sang-Ho 고려대학교 아세아문제연구소 2001 亞細亞硏究 Vol.44 No.1

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.

제주 성상 S/S MTr #1 행원 풍력단지 전압해석

김상준(Sang-Jun Kim),조민호(Min-Ho Cho),윤기갑(Gi-Gab Yoon),장상옥(Sang-Ok Jang),안정식(Jeong-Shik Ahn) 대한전기학회 2003 대한전기학회 학술대회 논문집 Vol.2003 No.11

Skin entrance dose for digital and film radiography in Korean dental schools

Cho, Eun-Sang,Choi, Kun-Ho,Kim, Min-Gyu,Lim, Hoi-Jeong,Yoon, Suk-Ja,,Kang, Byung-Cheol 대한구강악안면방사선학회 2005 Imaging Science in Dentistry Vol.35 No.4

Purpose : This study was aimed to compare skin entrance dose of digital radiography with that of film radiography and to show the dose reduction achievement with digital systems at 11 dental schools in Korea. Materials and Methods : Forty six intraoral radiographic systems in 11 dental schools were included in this study. Digital sensors were used in 33 systems and film was used in 13 systems. Researchers and the volunteer visited 11 dental schools in Korea. Researchers asked the radiologic technician (s) at each school to set the exposure parameters and aiming the x-ray tube for the periapical view of the mandibular molar of the volunteer. The skin entrance doses were measured at the same exposure parameters and distance by the technician for each system with a dosimeter (Multi-O-Meter : Unfors instruments, Billdal, Sweden). Results : The median dose was 491.2 μGy for digital radiography and 1,205.0 μGy for film radiography. The skin entrance dose digital radiography was significantly lower than that of film radiography (p<0.05). Conclusion : Fifty-nine percent skin entrance dose reduction with digital periapical radiography was achieved over the film radiography in Korean dental schools.

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]

Implication of necrosis-linked p53 aggregation in acquired apoptotic resistance to 5-FU in MCF-7 multicellular tumour spheroids

Lee, Su Yeon,Jeong, Eui-Kyong,Jeon, Hyun Min,Kim, Cho Hee,Kang, Ho Sung Spandidos Publications 2010 Oncology reports Vol.24 No.1

<P>Three-dimensional (3D) multicellular tumour spheroids (MTS) have been used as an in vitro model of solid tumours for drug resistance studies because they mimic the growth characteristics of in vivo tumours more closely than in vitro two-dimensional (2D) culture of cancer cell lines. As observed in solid tumours, MTS exhibits a proliferation gradient with outer regions consisting of proliferating cells that surround inner quiescent cells. The innermost cells in core regions undergo cell death mostly by necrosis to form necrotic core due to insufficient supply of oxygen and nutrient such as glucose with increasing size of spheroids. Tumour necrosis is thought to indicate a poor prognosis and to contribute to acquisition of chemoresistance in solid tumours; however, the mechanism underlying necrosis-mediated chemoresistance remains unclear. In this study, we examined the chemoresistance to 5-Fluorouracil (5-FU) using MCF-7 breast cancer MTS. 5-FU (400 microM) induced apoptosis in MCF-7 cell monolayer as determined by HO/PI staining, PARP cleavage, p53 induction, Bax induction, and Bcl-2 down-regulation. When MCF-7 breast tumour spheroids were cultured on agarose for 8 days, they reached approximately 700 microm in diameter, with a necrotic core. We found that 5-FU-induced apoptosis is markedly reduced in spheroids that were cultured for 9 days and had necrotic core, compared with MCF-7 monolayer cells and spheroids that were cultured for 6 days and had no necrotic core, indicating that the formation of necrotic core may be linked to acquisition of chemoresistance to 5-FU. We also found that a specific set of cellular proteins including p53 was aggregated into a RIPA-insoluble form during MTS culture. Furthermore, most of p53 induced by 5-FU was aggregated in MTS with necrotic core. Our results suggest that necrosis-linked p53 aggregation may contribute to acquired apoptotic resistance to 5-FU in MTS model system.</P>