Prostaglandin A₂-induced Apoptosis is Not Inhibited by Heme Oygenase-1 in U2OS Cells

Kyoung-Won Ko(고경원),Sun-Young Lee(이선영),Ji-Hyun Ahn(안지현),Jaetaek Kim(김재택),In-Kyung Kim(김인경),Ho-Shik Kim(김호식) 한국생명과학회 2008 생명과학회지 Vol.18 No.11

Prostaglandin A₂ (PGA₂)는 사람 골육종 세포인 U2OS 세포주에서 apoptosis와 heme oxygenase (HO)-1의 발현을 함께 유도하였다. PGA₂에 의한 apoptosis는 HO-1의 과도한 발현이나 HO-1에 대한 small interfering RNA에 의한 발현저하에 의하여 변동되지 않았으나 H₂O₂에 의한 세포사망은 HO-1의 발현 수준에 반비례하여 변동되었다. 또한 thiol antioxidant인 N-acetyl-L-cysteine (NAC)은 PGA₂에 의한 세포사망과 HO-1의 발현 증가를 모두 차단하였지만, non-thiol antioxidant인 butylated hydroxyanisole (BHA)과 ascorbic acid는 세포사망과 HO-1의 발현 유도를 차단하지 않았다. 이와 같은 결과들은 PGA₂는 산화성 손상에 의해서가 아니라 PGA₂의 thiol-reactivity에 의하여 apoptosis와 HO-1의 발현을 유도하며, HO-1의 발현은 PGA₂에 의한 apoptosis와는 독립적인 현상이거나 기능적으로 apoptosis 유도의 하부에 위치하고 apoptosis의 진행에는 기여하지 않을 것이라는 것을 시사해 준다. Prostaglandin A₂ (PGA₂), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. PGA₂-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas H₂O₂-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by PGA₂. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that PGA₂ induces both apoptosis and HO-1 expression, which are critically related to the thiol-reactivity of PGA₂, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by PGA₂ without contribution to apoptosis progression.

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.

Sulforaphane protects against acetaminophen-induced hepatotoxicity

Noh, Jung-Ran,Kim, Yong-Hoon,Hwang, Jung Hwan,Choi, Dong-Hee,Kim, Kyoung-Shim,Oh, Won-Keun,Lee, Chul-Ho Elsevier 2015 Food and chemical toxicology Vol.80 No.-

<P><B>Abstract</B></P> <P>Oxidative stress is closely associated with acetaminophen (APAP)-induced toxicity. Heme oxygenase-1 (HO-1), an antioxidant defense enzyme, has been shown to protect against oxidant-induced tissue injury. This study investigated whether sulforaphane (SFN), as a HO-1 inducer, plays a protective role against APAP hepatotoxicity <I>in vitro</I> and <I>in vivo</I>. Pretreatment of primary hepatocyte with SFN induced nuclear factor E2-factor related factor (Nrf2) target gene expression, especially HO-1 mRNA and protein expression, and suppressed APAP-induced glutathione (GSH) depletion and lipid peroxidation, which eventually leads to hepatocyte cell death. A comparable effect was observed in mice treated with APAP. Mice were treated with 300 mg/kg APAP 30 min after SFN (5 mg/kg) administration and were then sacrificed after 6 h. APAP alone caused severe liver injuries as characterized by increased plasma AST and ALT levels, GSH depletion, apoptosis, and 4-hydroxynonenal (4-HNE) formations. This APAP-induced liver damage was significantly attenuated by pretreatment with SFN. Furthermore, while hepatic reactive oxygen species (ROS) levels were increased by APAP exposure, pretreatment with SFN completely blocked ROS formation. These results suggest that SFN plays a protective role against APAP-mediated hepatotoxicity through antioxidant effects mediated by HO-1 induction. SFN has preventive action in oxidative stress-mediated liver injury.</P> <P><B>Highlights</B></P> <P> <UL> <LI> SFN pretreatment increases the cell viability against APAP-induced toxicity. </LI> <LI> SFN pretreatment protects depletion of cellular GSH after APAP treatment. </LI> <LI> SFN pretreatment enhances Nrf2 target gene expression, especially HO-1 after APAP treatment. </LI> <LI> SFN has protective effect against APAP overdose-induced liver injury <I>in vivo</I> model as well. </LI> </UL> </P>

Sauchinone Suppresses Pro-inflammatory Mediators by Inducing Heme Oxygenase-1 in RAW264.7 Macrophages

Li, Bin,Lee, Dong-Sung,Choi, Hyun-Gyu,Kim, Kyoung-Su,Kang, Dae-Gil,Lee, Ho-Sub,Jeong, Gil-Saeng,Kim, Youn-Chul Pharmaceutical Society of Japan 2011 BIOLOGICAL & PHARMACEUTICAL BULLETIN Vol.34 No.10

<P>Sauchinone, a biologically active lignan isolated from the roots of <I>Saururus chinensis</I> (L<SMALL>OUR</SMALL>.) B<SMALL>AILL</SMALL>. (Saururaceae), is reported to exert a variety of biological activities, such as hepatoprotective, anti-inflammatory actions and inhibitory effects on bone resorption. In this study, we investigated the effect of sauchinone in suppressing cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, leading to a reduction in COX-2-derived prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) and iNOS-derived nitric oxide (NO) production in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. Present study also demonstrates the effects of sauchinone in inducing heme oxygenase-1 (HO-1) expression and an increase in heme oxygenase (HO) activity in RAW264.7 macrophages. The effects of sauchinone on LPS-induced PGE<SUB>2</SUB>, NO, tumor necrosis factor-α (TNF-α) and interlukine-1β (IL-1β) production were partially reversed by the HO-1 inhibitor Tin protoporphyrin was also seen in this study. In addition, we found that treatment with extracellular signal-regulated kinase (ERK) inhibitor (PD98059) reduced sauchinone-induced HO-1 expression. Sauchinone also increased ERK phosphorylation. These results suggest that sauchinone inhibits pro-inflammatory mediators through expression of anti-inflammatory HO-1 <I>via</I> ERK pathway.</P>

3-(1,2,4-Triazol-5-yl)methylene-2-oxo-1,2,3,4,-tetrahydroquinoxaline의 간편한 합성에 관한 연구

金浩植,金恩慶,李城旭,金成湜,金銅恩 대구효성가톨릭대학교 1996 연구논문집 Vol.53 No.2

The reaction of 3-methoxycarbonylmethylene-2-oxo-1,2,3,4-tetrahydroquinoxaline(14) with hydrazine hydrate gave 3-hydrazinocarbonyl-methylene-2-oxo-1,2,3,4-tetrahydroquinoxaline(15), whose reaction with phenyl isothiocyanate provided 3-(4-phenyl-3,4-dihydro-3-thioxo-2H-1,2,4-triazol-5-yl)methylene-2-oxo-1,2,3,4-tetrahydroquinoxaline(16). The tautomeric behavior of compound 15 was investigated on the basis of the tautomer ratio determined by the ¹H-nmr spectral data. The structures of the synthesized compounds were confirmed on the basis of ir, ¹H-nmr and mass spectral data.

Improvement of adhesion properties of glass prepared using SiC‑deposited graphite mold via low‑temperature chemical vapor deposition

Kyoung‑Ho Kim,Kuk‑Jin Hwang,Heesoo Lee,Seong‑Min Jeong,이명현,배시영 한국세라믹학회 2020 한국세라믹학회지 Vol.57 No.1

Compression glass molding is a promising technique for mass production of near net-shaped, high-precision, and low-cost optical glass elements. However, the glass molding process causes the damage of glass and the mold during demolding because of the chemical or physical adhesion of the glass to the mold. To overcome this limitation, graphite molds are used owing to their good lubrication and easy machining. However, graphite materials show rapid oxidation at high temperatures in the presence of oxygen. Therefore, in this study, a thin SiC coating layer was deposited on the graphite mold using the chemical vapor deposition (CVD) method to utilize the lubrication properties of graphite and the anti-oxidation properties of SiC. The specimen obtained using the low-temperature CVD method showed high carbon content and good lubrication properties than that obtained using the high-temperature CVD method.

Gas Chromatography를 이용한 Methoxime tert.-butyldimethylsilyl 유도체로서 α-Keto Acids의 분석에 관한 연구

金京禮,金正浩,金正漢,吳昌桓,黃恩卿 성균관대학교 약학연구소 1991 成均藥硏論文集 Vol.3 No.1

Abstract-Thirteen α-keto acids which are biochemically important were converted to methoxime(MO) derivatives with MOX and then to tert.-butyldimethylsilyl(TBDMS) derivatives using MTBS-TFA in isooctance prior to dual capillary column GC analysis. Single symmetric peaks were obtained for each MO TBDMS α-keto acids on the dual chromatograms. Optimum methoximation required heating at 60℃ for 2 hours and TBDMS derivatization required heating for 30 minutes. MO α-keto acids were stable during the tert.-butyldimethylsilylation and the methoximation of carbonyl group prevented silylation of enols. Mass spectrometric analysis of MO TBDMS derivatives was performed for structure identification. Base peaks at [M-57], intense ions at m/z=89, and weak ions at [M-15] were present in all spectra. The ions at m/z=89 were characteristic for α-keto acids.

일렬 자가조혈모세포이식을 받은 다발성 골수종 환자에서 발생한 뇌 톡소포자충증 1례

김계형,송경호,전재현,박완범,박상원,김홍빈,김남중,김인호,오명돈 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Toxoplasmosis is a rare but fatal complication in hematopoietic stem cell transplant recipients, usually associated with allogeneic hematopoietic stem cell transplantation (HSCT). We report a case of cerebral toxoplasmosis in a patient with multiple myeloma, following tandem autologous stem cell transplantation. A 55-year-old Korean male presented with weakness in both legs that had progressed to both arms. A magnetic resonance imaging scan of the brain revealed multiple, variablesized ring-enhancing lesions with surrounding edema in the cerebral hemispheres and brain stem. Stereotactic biopsy revealed bradyzoites of Toxoplasma gondii in the brain tissue. The patient received trimethoprim-sulfamethoxazole, followed by pyrimethamine and sulfadiazine, accompanying treatment for progressive multiple myeloma. Cerebral toxoplasmosis should be considered as one of the differential diagnoses in patients with neurologic signs following autologous HSCT.

반복적인 부비동염으로 내원한 Good 증후군 1예

송경호,김계형,김충종,박경운,전상훈,김홍빈,김남중,오명돈,최강원 대한감염학회 2007 감염과 화학요법 Vol.39 No.5

Good 증후군은 흉선종과 면역결핍이 동반되는 질환으로, B세포의 감소로 인한 범저감마글로불린혈증과 CD4^(+)T세포의 감소로 인한 세포성 면역저하가 동시에 나타나는 것을 특징으로 한다. 본 증례는 18개월 전부터 발생한 반복적인 부비동염을 주소로 내원한 43세 남자 환자로, 내원 1년 전 흉선종절제수술을 시행받았으며, 면역학적 검사상 범저감마글로불린혈증과 T세포의 감소 등의 이상 소견이 발견되었다. 정주 면역글로불린과 경험적 항생제(amoxicillin/clavulanic acid) 사용 후 부비동염이 호전되었으며, 예방접종과 정기적인 면역글로불린 투여 후 특이 합병증없이 경과 관찰 중이다. Good's syndrome is the association of thymoma with immunodeficiency, characterized by hypogammaglobulinemia, B-cell lymphopenia and variably defects in cellular immunity with CD4^(+) T-cell lymphopenia and an inverted CD4^(+):CD8^(+) T-cell ratio. We report a 43-year-old male patient who presented with a 18-month history of productive cough and postnasal drip. One year ago, he underwent the operation for resection of a thymoma. Despite of appropriate management, sinusitis relapsed multiple times. He was found to have hypogammaglobulinemia with nearly absent B cells(4/μL). The CD4^(+) T-cell count was 554/μL with an inverted CD4^(+):CD8^(+) T-cell ratio of 0.6. His symptoms and signs improved with antibiotic treatment and monthly administration of intravenous immunoglobulin (IVIG, 400 mg/kg).

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.