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.

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.

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>

Comparison of Treatment Goals for Moderate-to-Severe Psoriasis between Korean Dermatologists and the European Consensus Report

( Sang Woong Youn ),( Bo Ri Kim ),( Joo Heung Lee ),( Hae Jun Song ),( Yong Beom Choe ),( Ji Ho Choi ),( Nack In Kim ),( Kwang Joong Kim ),( Jai Il Youn ) 대한피부과학회 2015 Annals of Dermatology Vol.27 No.3

Background: The development of therapies for psoriasis has led to the need for a new strategy to the treatment of patients with moderate-to-severe psoriasis. New consensus guidelines for psoriasis treatment have been developed in some countries, some of which have introduced treatment goals to determine the timing of therapeutic regimens for psoriasis. Objective: To investigate the opinions held by Korean dermatologists who specialize in psoriasis about treatment goals, and to compare these with the European consensus. Methods: Korean dermatologists who specialize in psoriasis were asked 11 questions about defining the treatment goals for psoriasis. The questionnaire included questions about the factors used to classify the severity of psoriasis, defining the induction and maintenance phases of psoriasis treatment, defining treatment responses during the induction phase, and defining treatment responses during the maintenance phase. Results: The Korean consensus showed responses that were almost similar to the European consensus, even without using the Delphi technique, which uses repeated rounds of questions to reach a consensus. Only one response that related to psoriasis severity in the context of the quality of patients` lives differed from the European consensus. Conclusion: The concept of using treatment goals in the treatment of moderate-to-severe psoriasis can be applied to Korean psoriasis patients. Since a tool for assessing the quality of patients` lives is not commonly used in Korea, the development of a simple, rapidly completed, and region-specific health-related quality of life assessment tool would enable treatment goals to be used in routine clinical practice. (Ann Dermatol 27(2) 184∼189, 2015)

Clinical Course of Patients With Mediastinal Lymph Node Tuberculosis and Risk Factors for Paradoxical Responses

Choe Junsu,Han Areum,Shin Sun Hye,Lee Kyungjong,Um Sang-Won,Kim Hojoong,Kim Tae Yeul,Huh Hee Jae,Choi Yoon-La,Han Joungho,Jeong Byeong-Ho 대한의학회 2023 Journal of Korean medical science Vol.38 No.47

Background: Paradoxical responses (PR) occur more frequently in lymph node tuberculosis (LNTB) than in pulmonary tuberculosis and present difficulties in differential diagnosis of drug resistance, new infection, poor patient compliance, and adverse drug reactions. Although diagnosis of mediastinal LNTB has become much easier with the development of endosonography, limited information is available. The aim of this study was to investigate the clinical course of mediastinal LNTB and the risk factors associated with PR. Methods: Patients diagnosed with mediastinal LNTB via endosonography were evaluated retrospectively between October 2009 and December 2019. Multivariable logistic regression was applied to evaluate the risk factors associated with PR. Results: Of 9,052 patients who underwent endosonography during the study period, 158 were diagnosed with mediastinal LNTB. Of these, 55 (35%) and 41 (26%) concurrently had pulmonary tuberculosis and extrapulmonary tuberculosis other than mediastinal LNTB, respectively. Of 125 patients who completed anti-tuberculosis treatment, 21 (17%) developed PR at a median of 4.4 months after initiation of anti-tuberculosis treatment. The median duration of anti-tuberculosis treatment was 6.3 and 10.4 months in patients without and with PR, respectively. Development of PR was independently associated with age < 55 years (adjusted odds ratio [aOR], 5.72; 95% confidence interval [CI], 1.81–18.14; P = 0.003), lymphocyte count < 800/μL (aOR, 8.59; 95% CI, 1.60–46.20; P = 0.012), and short axis diameter of the largest lymph node (LN) ≥ 16 mm (aOR, 5.22; 95% CI, 1.70–16.00; P = 0.004) at the time of diagnosis of mediastinal LNTB. Conclusion: As PR occurred in one of six patients with mediastinal LNTB during antituberculosis treatment, physicians should pay attention to patients with risk factors (younger age, lymphocytopenia, and larger LN) at the time of diagnosis.

Bartholdi zeta and <i>L</i>-functions of weighted digraphs, their coverings and products

Choe, Young-Bin,Kwak, Jin Ho,Park, Yong Sung,Sato, Iwao Elsevier 2007 Advances in mathematics Vol.213 No.2

<P><B>Abstract</B></P><P>Since a zeta function of a regular graph was introduced by Ihara [Y. Ihara, On discrete subgroups of the two by two projective linear group over <I>p</I>-adic fields, J. Math. Soc. Japan 19 (1966) 219–235], many kinds of zeta functions and <I>L</I>-functions of a graph or a digraph have been defined and investigated. Most of the works concerning zeta and <I>L</I>-functions of a graph contain the following: (1) defining a zeta function, (2) defining an <I>L</I>-function associated with a (regular) graph covering, (3) providing their determinant expressions, and (4) computing the zeta function of a graph covering and obtaining its decomposition formula as a product of <I>L</I>-functions. As a continuation of those works, we introduce a zeta function of a weighted digraph and an <I>L</I>-function associated with a weighted digraph bundle. A graph bundle is a notion containing a cartesian product of graphs and a (regular or irregular) graph covering. Also we provide determinant expressions of the zeta function and the <I>L</I>-function. Moreover, we compute the zeta function of a weighted digraph bundle and obtain its decomposition formula as a product of the <I>L</I>-functions.</P>

Novel Washing-free and Label-free Electrochemical Detection Method for Target DNA Utilizing Peroxidase Mimicking DNAzyme

Sang Mo LEE,Sujeong SHIN,Jaemin KIM,Sunghyeon KIM,Jong Chan CHOE,Ho Don JEONG,Ki Soo PARK,Hyun Gyu PARK 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.4

Centrosome Clustering Is a Tumor-selective Target for the Improvement of Radiotherapy in Breast Cancer Cells

CHOE, MIN HO,KIM, JOON,AHN, JIYEON,HWANG, SANG-GU,OH, JEONG SU,KIM, JAE-SUNG Potamitis Press 2018 Anticancer research Vol.38 No.6

Adsorbed Carbon Formation and Carbon Hydrogenation for CO2 Methanation on the Ni(111) Surface: ASED-MO Study

Sang Joon Choe*,Hae Jin Kang,Su-Jin Kim,Sung-Bae Park,Dong Ho Park,Do Sung Huh 대한화학회 2005 Bulletin of the Korean Chemical Society Vol.26 No.11

Using the ASED-MO (Atom Superposition and Electron Delocalization-Molecular Orbital) theory, we investigated carbon formation and carbon hydrogenation for CO2 methanation on the Ni (111) surface. For carbon formation mechanism, we calculated the following activation energies, 1.27 eV for CO2 dissociation, 2.97 eV for the CO, 1.93 eV for 2CO dissociation, respectively. For carbon methanation mechanism, we also calculated the following activation energies, 0.72 eV for methylidyne, 0.52 eV for methylene and 0.50 eV for methane, respectively. We found that the calculated activation energy of CO dissociation is higher than that of 2CO dissociation on the clean surface and base on these results that the CO dissociation step are the rate-determining of the process. The C-H bond lengths of CH4 the intermediate complex are 1.21 Å, 1.31 Å for the C…H(1), and 2.82 Å for the height, with angles of 105o for  H(1)CH and 98o for H(1)CH(1).