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 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration

Bae, Gi-Sang,Kim, Dong-Goo,Jo, Il-Joo,Choi, Sun-Bok,Kim, Myoung-Jin,Shin, Joon Yeon,Kim, Dong-Uk,Song, Ho-Joon,Joo, Myungsoo,Park, Sung-Joo ELSEVIER 2019 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.69 No.-

<P><B>Abstract</B></P> <P>Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 μg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Desoxo-narchinol-A (DN) is a natural compound of HO-1 inducer in pancreas. </LI> <LI> Mechanism of DN-induced HO-1 is mediated by MAPK/Activator Protein-1/HO-1 signaling. </LI> <LI> DN-induced HO-1 blocks neutrophil infiltration into pancreas via inhibition of CXCL2. </LI> <LI> DN inhibits cerulein-induced acute pancreatitis (AP) and AP-associated lung injury. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

실용음악 전공 학생들의 발성치료 전후 성대 및 음성 특성 비교

황연신,심미란,김철준,최용석,김상연,최찬호,선동일,Hwang, Yeon Shin,Shim, Mi Ran,Kim, Chul Jun,Choi, Yong Suk,Kim, Sang Yeon,Choi, Chan Ho,Sun, Dong Il 대한후두음성언어의학회 2016 대한후두음성언어의학회지 Vol.27 No.2

Background and Objectives : Many students major in applied music singing have various difficulties in phonation when they sing or perform. But the studies about this cause are lack. The purpose of this study is whether singing voice therapy based on vocal music is effective or not to applied music singing students that have difficulties in phonation. Materials and Methods : Singing voice therapy program had been done to 8 students major in applied music singing during 7 weeks. We did laryngeal stroboscope, perceptual, acoustic and aerodynamic examination before and after singing voice therapy to this students. And we studied post examination results have differences or improvements compared to pre examination results. Results : Four male students don't have effective improvement after singing voice therapy but they shows slight improvement in aerodynamic examination values compared to pre examination values. Four female students shows improvement in aerodynamic examination values and pitch range increasing. Above all, one student's vocal nodules disappeared after singing voice therapy. Conclusion : Singing voice therapy based on music singing is very effective to the students major in applied music singing. Above all, their curriculum in applied music singing should include phonation training based on music singing before training perform and technic practices.

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 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]

Characterization of Silver Inkjet Overlap-printing through Cohesion and Adhesion

Sang?Ho Lee,Young?June Cho 대한전기학회 2012 Journal of Electrical Engineering & Technology Vol.7 No.1

We introduce an understanding of silver (Ag) inkjet overlap-printing characteristics from the viewpoints of cohesion between ink droplets and adhesion between an ink droplet and a surface. The printing characteristics were closely monitored by changing the surface energy to elucidate the effect of adhesion and cohesion on printing instability, such as droplet merging and line bulging. The surface energy of the substrate was changed through the hydrophilization of a hydrophobic fluorocarbon-coated surface. The surface energy and ink wettability of the prepared surfaces were characterized using sessile drop contact angle analysis, and printing instability was observed using an optical microscope after drop-on-demand inkjet printing with a 50% overlap in diameter of deposited singlet patterns. We found that the surface energy is not an appropriate indicator based on the experimental results of Ag ink printing on a hydrofluoric-treated silicon surface. The analytical approach using adhesion and cohesion was helpful in understanding the instability of the inkjet overlap-printing, as adhesion and cohesion represent the direct interfacial relationship between the Ag inks used and the substrate.

Effect of Mn and C on Age Hardening of Fe–Mn–Al–C Lightweight Steels

Sung‑Won Park,Jun Young Park,Kyong Mox Cho,Jae Hoon Jang,Seong‑Jun Park,Joonoh Moon,Tae‑Ho Lee,Jong‑Ho Shin 대한금속·재료학회 2019 METALS AND MATERIALS International Vol.25 No.3

The effects of Mn and C content on the age hardening of Fe–Mn–Al–C lightweight steels, which have austenitic or duplex(austenite and ferrite) microstructures, were investigated. An increase in Mn content induced a delay of the age hardeningthat is caused by the formation of intra-granular κ-carbides. In order to interpret the effect of Mn content, first-principlescalculations were conducted using the supercells of Fe24Al8C8,Fe24Al8C7,Fe24(Al7Mn)C8, and Fe24(Al7Mn)C7. The calculationsshowed that an increase in Mn content could be the source of the delay of the intra-granular κ-carbide formation bysuppressing C atom’ occupation of the vacancy at the body-centered site of L12. An increase in C content accelerated theformation of intra-granular κ-carbides, which induced the intense age hardening, and coarse inter-granular κ-carbides, whichresulted in significant decrease in impact absorbed energy due to inter-granular fracture.

Fatigue Crack Growth Behavior in Ultrafine Grained Low Carbon Steel

Ho,Kyung Kim,Myung-Il Choi,Chin-Sung Chung Dong-Hyuk Shin 대한기계학회 2002 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.16 No.10

Ultrafine grained (UFG) low carbon (0.15 wt.% C) steel produced by equal channel angular pressing (ECAP) was tested for investigating the effect of load ratio on the fatigue crack growth rate. Fatigue crack growth resistance and threshold of UFG steel were lower than that of as-received coarse grained steel. It was attributed to the less tortuous crack path. The UFG steel exhibited slightly higher crack growth rates and a lower △K_th with an increase of R ratio. The R ratio effect on crack growth rates and △K_th was basically indistinguishable at lower load ratio (R>0.3), compared to other alloys, which indicates that contribution of the crack closure vanishes. The crack growth rate curve for UFG steel exhibited a longer linear extension to the lower growth rate regime than that for the coarse grained as-received steel.<br/>

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.

사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예

배상훈 ( Sang Hoon Bae ),김동현 ( Dong Hyun Kim ),배영석 ( Young Seok Bae ),이광재 ( Kwang Jae Lee ),김동완 ( Dong Wan Kim ),윤정빈 ( Jeoung Bin Yoon ),홍준호 ( Joon Ho Hong ),김상현 ( Sang Hyun Kim ) 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.2

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.