Carbon monoxide prevents TNF-α-induced eNOS downregulation by inhibiting NF-κB-responsive miR-155-5p biogenesis

Choi, Seunghwan,Kim, Joohwan,Kim, Ji-Hee,Lee, Dong-Keon,Park, Wonjin,Park, Minsik,Kim, Suji,Hwang, Jong Yun,Won, Moo-Ho,Choi, Yoon Kyung,Ryoo, Sungwoo,Ha, Kwon-Soo,Kwon, Young-Guen,Kim, Young-Myeong Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>Heme oxygenase-1-derived carbon monoxide prevents inflammatory vascular disorders. To date, there is no clear evidence that HO-1/CO prevents endothelial dysfunction associated with the downregulation of endothelial NO synthesis in human endothelial cells stimulated with TNF-α. Here, we found that the CO-releasing compound CORM-2 prevented TNF-α-mediated decreases in eNOS expression and NO/cGMP production, without affecting eNOS promoter activity, by maintaining the functional activity of the <I>eNOS</I> mRNA 3′-untranslated region. By contrast, CORM-2 inhibited MIR155HG expression and miR-155-5p biogenesis in TNF-α-stimulated endothelial cells, resulting in recovery of the 3′-UTR activity of <I>eNOS</I> mRNA, a target of miR-155-5p. The beneficial effect of CORM-2 was blocked by an NF-κB inhibitor, a miR-155-5p mimic, a HO-1 inhibitor and siRNA against HO-1, indicating that CO rescues TNF-α-induced eNOS downregulation through NF-κB-responsive miR-155-5p expression via HO-1 induction; similar protective effects of ectopic HO-1 expression and bilirubin were observed in endothelial cells treated with TNF-α. Moreover, heme degradation products, except iron and <I>N</I>-acetylcysteine prevented H<SUB>2</SUB>O<SUB>2</SUB>-mediated miR-155-5p biogenesis and eNOS downregulation. These data demonstrate that CO prevents TNF-α-mediated eNOS downregulation by inhibiting redox-sensitive miR-155-5p biogenesis through a positive forward circuit between CO and HO-1 induction. This circuit may play an important preventive role in inflammatory endothelial dysfunction associated with human vascular diseases.</P>

Production and characterization of soluble human TNFRI-Fc and human HO-1(HMOX1) transgenic pigs by using the F2A peptide

Park, Sol Ji,Cho, Bumrae,Koo, Ok Jae,Kim, Hwajung,Kang, Jung Taek,Hurh, Sunghoon,Kim, Su Jin,Yeom, Hye Jung,Moon, Joonho,Lee, Eun Mi,Choi, Ji Yei,Hong, Ju Ho,Jang, Goo,Hwang, Joing-Ik,Yang, Jaeseok,Le Springer-Verlag 2014 Transgenic research Vol.23 No.3

ORiginal Article : Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

( Yoon Jeong Choi ),( Nayoung Kim ),( Ju Yup Lee ),( Ryoung Hee Nam ),( Ji Hyung Seo ),( Seonmin Lee ),( Hee Jin Kim ),( Yoon Jin Choi ),( Hye Seung Lee ),( Dong Ho Lee ) 대한간학회 2016 Gut and Liver Vol.10 No.3

Background/Aims: This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-Lcysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. Methods: Sprague- Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanolonly group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor a, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. Results: PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMKS005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. Conclusions: These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes. (Gut Liver 2016;10:348- 355)

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]

The Antioxidant Effect of the Rhaponticum uniflorum Extracts on the Oxidative Stress in H₂O₂ induced Human Keratinocytes

So Hee Ahn,Won Yeoung Choi,Ji Won Jeong,Geon Woo Park,Su Yeon Kang,Eun Jeong Kim,Su Rim Sin,Eun Seo Jang,Gye Won Lee,Young Ho Cho 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

In this study, To investigate the antioxidant activities of Rhaponticum uniflorum extracts (RUE), we assessed scavenging activities on DPPH, ABTS radicals, and reducing power. The DPPH and ABTS radical scavenging activities (SC50) of RUE were 96.97±1.19 μg/mL and 31.26±0.13 μ g/mL, respectively, and the reducing power significantly increased dose-dependent manner. To study the antioxidant effecters of RUE in H₂O₂ induced human keratinocytes, expression of Nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined by Western blot and qRT-PCR. RUE induced the expression of HO-1, a critical target enzyme of Nrf2, in a concentration-dependent manner. The expression of HO- 1 mRNA was also induced in H₂O₂-treated HaCaT cells but no significant difference in the level of HO-1 mRNA was observed. Taken together, these results suggest that RUE may be useful as a potential ingredient for anti-aging products.

Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

Lee, Yoo-hwan,Kim, Jung-hee,Song, Choon-ho,Jang, Kyung-jeon,kim, Cheol-hong,Kang, Ji-Sook,Choi, Yung-hyun,Yoon, Hyun-Min KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.1

Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, $H_2O_2$) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and $H_2O_2$ in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and $H_2O_2$-induced growth inhibition. Results: The results showed that EGL effectively inhibited $H_2O_2$-induced growth and the generation of ROS. EGL markedly suppressed $H_2O_2$-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 ($p-{\gamma}H2AX$), a widely used marker of DNA damage, suggesting that EGL prevented $H_2O_2$-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against $H_2O_2$-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from $H_2O_2$-induced oxidative cytotoxicity.

부산·울산·경남지역 직업병 감시체계

김정일,김병권,김정원,채창호,이철호,강동묵,김지홍,김진하,김영욱,이영하,이지호,김정호,윤형렬,유철인,정백근,장태원,김운규,윤동영,강진욱,김종은,안진홍,이동준,장준호,이광영,송혜란,최영희,이용환,조병만,최홍렬,고상백,김은아,이유진,홍영습,정갑열,김정만,김준연 大韓産業醫學會 2004 대한직업환경의학회지 Vol.16 No.1

Objective: Occupational medicine specialists in the Busan, Ulsan and Kyung-Nam areas established an area-based occupational disease surveillance system and used this system to collected case information for the purpose of preventing occupational diseases Methods: l l hospital participated in this system. The authors selected five main diseases, which were hand-arm vibration syndrome (HAVS), work-related musculoskeletal disorder (WRMSD), occupational asthma, occupational skin disease and occupational and occupational lung cancer and established their case definitions. All cases were reported on the web, and real time analysis was conducted. Results: Between April 2001 and April 2003, 192 cases of HAVS, 118 cases of WRMSD, 33 cases of occupational asthma, 17 cases of occupational skin disease and 17 cases of occupational lung cancer (for a total of 377 cases of these five main diseases) were reported. most of the HAVS cases came from shipbuilding, and 172 of them (92.7%) were associated with grinding. Of the four main types of WRMSD, carpal tunnel syndrome (CTS) was the most prevalent with 46 cases and shipbuilding was also the main industry involved (83.9%). The ergonomic risk factors involved mainly associated with the hand. In 19 (57.6%) and 4 (12.1%) cases of occupational asthma, the agents involved. The causative agents of occupational lung cancer included Cr, welding fume, PAH, Ni, etc. 10(58.8%) of the cases were diagnosed as squamous cell carcinoma and 5(29.4%) as adenoma. Conclusion: This result showed that an area-based occupational disease surveillance system might provide an effective method of evaluating the prevalence of such diseases, however the Busan, Ulsan and Kyung-Nam provinces are too large to be treated as individual areas. Therefore, the authors suggest that each province should establish its own surveillance system.

Slide Session : OS-IFD-07 ; Infectious Disease : In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus

( Myung Jin Lee ),( Kye Hyung Kim ),( Jong Youn Yi ),( Su Jin Choi ),( Chung Jong Kim ),( Nak Hyun Kim ),( Kyoung Ho Song ),( Pyoeng Gyun Choi ),( Ji Hwan Bang ),( Wan Beom Park ),( Eu Suk Kim ),( San 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

In Vitro Antiviral Activity of Ribavirin Against Severe Fever with Thrombocytopenia Syndrome Virus Myung Jin LEE1, Kye-Hyung KIM1, Jongyoun YI2, SuJin CHOI1, Chung-Jong KIM1, Nak- Hyun KIM1, Kyoung-Ho SONG1, Pyoeng Gyun CHOI1, Ji-Hwan BANG1, Wan Beom PARK1, Eu Suk KIM1, Sang-Won PARK1, Hong Bin KIM1, Nam Joong KIM1, Myoung- Don OH1 Seoul National University College of Medicine, Korea1, Pusan National University School of Medicine, Korea2 Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV). No effective antiviral therapy is proven yet, but clinical use of ribavirin (RBV) has been tried. We investigated the antiviral effect of RBV against SFTSV in vitro. Methods: To test for cytotoxicity of RBV, Vero cells were treated with different concentrations of RBV (3.90 to 500 μg/mL, two-fold dilution) and analyzed by cell viability MTS assay 48h post-infection. To determine antiviral activity of RBV against SFTSV, Vero cells were infected with SFTSV strain Gangwon/Korea/2012 at 100 TCID50 (50% tissue culture infective dose) per well in a 96-well plate, and RBV was added at the concentrations showing no or minimal cytotoxicity. Viral RNAs were extracted from the culture supernatants and quantifi ed using one-step real-time reverse transcription- PCR to amplify the partial large segment of SFTSV. Statistical analysis was done by one-way ANOVA with Tukey`s post hoc test. Results: Cytotoxicity due to RBV was not observed at RBV concentration =31.3 μg/ mL. Viral RNAs at 24h post-RBV treatment were reduced with increasing RBV concentrations (1-32 μg/mL), compared with those of mock-treated cells (P <0.01, Figure). Half maximal inhibitory concentration (IC50) of RBV was 3.69 μg/mL at 24h post-RBV treatment. Conclusions: Our study shows that RBV has antiviral effect against SFTSV in a dose-dependent manner. Further studies are required to evaluate the effi cacy of RBV in SFTS.

우울증 환자의 부모양육행동, 대상관계 및 자아존중감에 관한 연구

최지애,최영민,이정호,이동우 大韓神經精神醫學會 2008 신경정신의학 Vol.47 No.5

Objectives : The aim of this study was to examine the relationship between the Object Relations, Parenting Behaviors, and Self-esteem with Depression. Methods : This study included 60 Depression patients and 90 healthy individuals. Parent Behavior Inventory (PBI), Bell Object Relation Inventory (BORI), Self-Esteem Scale (SES) and Beck Depression Inventory (BDI) were used for measuring parenting behaviors, object relations, self-esteem and severity of depression in orderly. Results : Depression was negatively associated wi self-esteem, and positively associated with four subscale of Object relation. Also, depression was positively associated with maternal intrusiveness, Parental negligence and negatively associated with maternal affection. The most potent variable to explain depression was self-esteem, and the second was insecure attachment. Maternal affection was the most explainable variable of self-esteem, and the most potent variable of insecure attachment was maternal intrusiveness. Correlation analysis with insecure attachment and self-esteem as control variable individually, there was weak correlation among variables. Conclusion : This study shows object relation, parent behavior, and self-esteem are related with depressive symptoms. Object relation (especially, insecure attachment) and self-esteem is more important and proximal cause in depression than Parental behavior. Result of the present study indicated that inadequate parental behavior m childhood foster insecure object relation and low self-esteem, then they contribute to depression through their interaction.

Plasma N-Terminal Pro-B-Type Natriuretic Peptide Is Predictive of Perioperative Cardiac Events in Patients Undergoing Vascular Surgery

( Ji Hyun Yang ),( Jin Ho Choi2 ),( Young Wook Ki ),( Dong Ik Kim ),( Duk Kyung Kim ),( Jeong Rang Park ),( Jae K. Oh ),( Seung Hyuk Choi ) 대한내과학회 2012 The Korean Journal of Internal Medicine Vol.27 No.3

Background/Aims: Identification of patients at high risk for perioperative cardiac events (POCE) is clinically important. This study aimed to determine whether preoperative measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict POCE, and compared its predictive value with that of conventional cardiac risk factors and stress thallium scans in patients undergoing vascular surgery. Methods: Patients scheduled for non-cardiac vascular surgery were prospectively enrolled. Clinical risk factors were identified, and NT-proBNP levels and stress thallium scans were obtained. POCE was the composite of acute myocardial infarction, congestive heart failure including acute pulmonary edema, and primary cardiac death within 5 days after surgery. A modified Revised Cardiac Risk Index (RCRI) was proposed and compared with NT-proBNP; a positive result for ischemia and a significant perfusion defect (≥ 3 walls, moderate to severely decreased, reversible perfusion defect) on the thallium scan were added to the RCRI. Results: A total of 365 patients (91% males) with a mean age of 67 years had a median NT-proBNP level of 105.1 pg/ mL (range of quartile, 50.9 to 301.9). POCE occurred in 49 (13.4%) patients. After adjustment for confounders, an NTproBNP level of>302 pg/mL (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.1 to 10.3; p<0.001) and a high risk by the modified RCRI (OR, 3.9; 95% CI, 1.6 to 9.3; p = 0.002) were independent predictors for POCE. Comparison of the area under the curves for predicting POCE showed no statistical differences between NT-proBNP and RCRI. Conclusions: Preoperative measurement of NT-proBNP provides information useful for prediction of POCE as a single parameter in high-risk patients undergoing noncardiac vascular surgery.