Heme oxygenase-1 mediated protective effect of methyl gallate on cadmium-induced cytotoxicity in cultured mouse mesangial cells

Cha, Seok-Ho,Suh, Chang-Kook The Korean Society of Toxicogenomics and Toxicopro 2010 Molecular & cellular toxicology Vol.6 No.2

To clarify the effect of a phytochemical, methyl gallate (MG) on a heavy metal (cadmium)-induced renal toxicity, cytotoxicity and the change of heme oxygenase-1 (HO-1) gene expression was studied using cultured mouse renal glomerular mesangial cells (MMC). By employing RT-PCR and Western blotting analysis, we have examined the HO-1 induction in MMCs that were treated with $Cd^{2+}$ and/or MG. Using MTT assay we have also examined the cytoprotective effect of HO-1 induction against the cytotoxicity caused by toxic dose of $Cd^{2+}$. In MMCs exposed to $Cd^{2+}$ and MG, expression of HO-1 (mRNA and protein) was increased in a concentration- and time-dependent manner. The increments of HO-1 mRNA and protein expressions by $Cd^{2+}$ and MG were inhibited by the treatment of the cells with actinomycin D, an inhibitor of transcription. The decreased viability of the cells by $Cd^{2+}$ was partially recovered by the treatment of MG and this recovery by the MG was reduced by the treatment of zinc protoporphyrin IX (a HO-1 inhibitor). From these results, methyl gallate might have cytoprotective effect on $Cd^{2+}$-induced cytotoxicity that is related with heme oxygenase-1 induction.

운동강도의 차이가 대장에서의 Heme oxygenase-1 발현에 미치는 영향: Oligonucleotide chip microarray analysis

최은주 ( Eun Ju Choi ),류호영 ( Ho Young Ryu ),차광석 ( Kwang Suk Cha ) 한국운동생리학회(구-한국운동과학회) 2012 운동과학 Vol.21 No.1

이 연구의 목적은 운동강도 차이에 의한 대장조직이 Heme oxygenase-1(HO-1)의 mRNA 발현에 어떠한 영향을 미치는지 규명하기 위해, Sprage-Dawley계 흰쥐를 대상으로 통제그룹(CON)과 저강도 운동그룹(LIE), 고강도 운동그룹(HIE)으로 구분하여 4주 동안 트레드밀운동 후 48시간 이후에 High through-put microarray analysis방법으로 다음과 같은 실험을 실시하였다. 본 실험은 Rat ABI oligo chip 26,857 개의 유전자 중 filtering을 통하여 12.079개 유전지를 선택하였고, 이 중 유의성 있는(p<.05) 유전자 12,072개를 선별하였으며, clustering분석 방법과 면역조직화학염색법에서도 HO-l이 운동강도에 따라 유의하게 발현하였다(p<.05). Microarray분석 후 RT-PCR로 확인한 결과 HO-I의 유전자 발현양상이 일치하는 결과를 얻었다. 이 실험의 결과로서 운동이 대장에서 HO-1 발현에 영향을 주는 것을 알 수 있었다. 운동이 대장에서의 mRNA 발현이 저강도 운동그룹(LIE)보다 고강도 운동그룹(HIE)에서 더 많이 발현되어지는 것으로 보아 고강도 운동에 의해 발생되는 산소라디칼을 HO-l의 유도를 통하여 적절히 제거함으로써 스스로 항상성을 유지하고 있는 것으로 생각되어진다. The purpose of this study is to identify how large intestine tissue effects to mRNA expression in Heme oxygenase-l (HO-1) due to differences in exercise intensity. To perform this experiment we divided Sprage-Dawley rats into 3 groups (control group (CON). low-intensity exercise group (LIE) and high-intensity exercise group (HIE)), and in 48 hours after 4 weeks treadmill exercise. the following experiment was performed with "High through-put micro array analysis methods" . 12,079 genes were chosen by filtering of the Rat ASI oligo chip 26.857 genes in this experiment Among 12.079 genes, we selected significant genes (p<.05) that were also expressed in the ways of clustering analysis and immunohistochemistry. With results of RT-PCR confirming and microarray analyzing, we derived that gene expression profiles of HO-l had been consistent. As a result of this experiment, we certainly identified that exercise effects to HQ-l expression in large intestine. mRNA expression was more expressed in high-intensity exercise group CHIE) than low-intensity exercise group (LIE), it seems that homeostasis maintains itself by properly removing oxygen radical. caused by high intensity exercise. through reduction of HO-l.

Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway

Lee, Moon Hee,Han, Min Ho,Lee, Dae-Sung,Park, Cheol,Hong, Su-Hyun,Kim, Gi-Young,Hong, Sang Hoon,Song, Kyoung Seob,Choi, Il-Whan,Cha, Hee-Jae,Choi, Yung Hyun UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.39 No.2

<P>In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and gamma H2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage. Furthermore, morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keapl) expression. Notably, these events were eliminated by transient transfection with Nrf2-specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by morin was mediated by the extracellular signal-regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK. Collectively, these results demonstrated that morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO-1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2,-induced oxidative cytotoxicity.</P>

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model

Yun Ho Jo,Hwan Lee,Myeong Hwan Oh,Gyeong Hee Lee,You Jin Lee,Ji Sun Lee,Min Jung Kim,Won Yong Kim,Jin Seong Kim,Dae Seok Yoo,Sang Won Cho,Seon Woo Cha,Mi Kyung Pyo 한국영양학회 2020 Nutrition Research and Practice Vol.14 No.4

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson"s trichrome, α-smooth muscle actin, and transforming growth factor-β1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts

Lee, Moon Hee,Cha, Hee-Jae,Choi, Eun Ok,Han, Min Ho,Kim, Sung Ok,Kim, Gi-Young,Hong, Su Hyun,Park, Cheol,Moon, Sung-Kwon,Jeong, Soon-Jeong,Jeong, Moon-Jin,Kim, Wun-Jae,Choi, Yung Hyun Spandidos Publications 2017 International journal of molecular medicine Vol.39 No.3

<P>Natural phytochemicals of plant origin, including flavonoids, have been found to be potent antioxidants providing beneficial effects against oxidative stress-related diseases. The present study was carried out to investigate the antioxidant properties of morin, a flavonoid originally isolated from the flowering plants of the Moraceae family. Superoxide dismutase (SOD)-like activity and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) radical scavenging activity were determined. We also investigated the cytoprotective effects of morin against hydrogen peroxide (H2O2)-induced DNA damage and apoptosis in V79-4 Chinese hamster lung fibroblasts. Our results demonstrated that morin had strong scavenging effects against ABTS' radicals with enhanced SOD activity, which varied in a dose-dependent manner. Morin was found to reduce H2O2-induced intracellular reactive oxygen species generation and nuclear DNA damage, and it recovered cell viability damaged by H2O2 via inhibition of mitochondrial dysfunction-mediated apoptosis. Notably, the treatment of V79-4 cells with morin markedly enhanced the expression of heme oxygenase-1 (HO-1) but not quinone oxidoreductase-1, which was associated with the increased expression and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the downregulation of Kelch-like ECH-associated protein 1 expression. Based on our findings, we conclude that morin effectively ameliorated oxidative stress-induced DNA damage through intrinsic free radical scavenging activity and activation of the Nrf2/HO-1 pathway.</P>

골수이식 후 골밀도 및 골대사의 변화 : 2년 추적관찰 2-Year Prospective Study

이원영,강무일,오은숙,오기원,한제호,손현식,윤건호,차봉연,이광우,손호영,강성구,신완식,민우성,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

Anti-Proliferative Effect of an Aqueous Extract of <i>Prunella vulgaris</i> in Vascular Smooth Muscle Cells

Hwang, Sun Mi,Lee, Yun Jung,Lee, Yong Pyo,Yoon, Jung Joo,Lee, So Min,Cha, Jeong Dan,Choi, Kyung Min,Kang, Dae Gill,Lee, Ho Sub Hindawi Publishing Corporation 2013 Evidence-based Complementary and Alternative Medic Vol.2013 No.-

<P>The abnormal proliferation of vascular smooth muscle cells (VSMCs) in arterial walls is an important pathogenic factor of vascular disorders such as diabetic atherosclerosis. We have reported the anti-inflammatory effect of an aqueous extract from <I>Prunella vulgaris</I> (APV) in vascular endothelial cell. In the present study, APV exhibited inhibitory effects on high glucose-stimulated VSMC proliferation, migration, and invasion activities, inducing G<SUB>1</SUB> cell cycle arrest with downregulation of cyclins and CDKs and upregulation of the CKIs, p21<SUP>waf1/cip1</SUP> and p27<SUP>kip1</SUP>. Furthermore, APV dose dependently suppressed the high glucose-induced matrix metalloproteinase activity. High glucose-induced phosphorylation of ERK, p38 MAPK, was decreased by the pretreatment of APV. NF-<I><I>κ</I></I>B activation by high glucose was attenuated by APV, as an antioxidant. APV attenuated the high glucose-induced decrease of nuclear factor E2-related factor-2 (Nrf2) translocation and heme oxygenase-1 (HO-1) expression. Intracellular cGMP level was also increased by APV treatment. These results demonstrate that APV may inhibit VSMC proliferation via downregulating ROS/NF-<I><I>κ</I></I>B /ERK/p38 MAPK pathways. In addition, APV has a beneficial effect by the interaction of Nrf2-mediated NO/cGMP with HO-1, suggesting that <I>Prunella vulgaris</I> may be useful in preventing diabetic atherosclerosis.</P>

조혈모세포이식술이 골수기질세포의 기원 및 조골세포로의 증식 및 분화에 미치는 효과

강무일,조성원,오은숙,백기현,이원영,오기원,김혜수,한제호,윤건호,차봉연,이광우,손호영,강성구,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

대규모 멀티컴퓨터의 유동적 설계를 위한 시뮬레이션 환경의 설계 및 구현

차호정 光云大學校 1995 論文集 Vol.24 No.-

본 논문은 대규모 분산 메모리 병렬컴퓨터의 유동적인 설계 및 성능 분석, 그리고 연관된 병렬 프로그램의 개발을 위한 병렬컴퓨터 시뮬레이터의 설계와 구현에 대해 논한다. 또한, 구현된 시뮬레이터의 기능 및 성능을 실제 하드웨어 환경을 바탕으로 검증한 결과를 기술한다. 본 시뮬레이션 시스템을 이용하여 가상 병렬 컴퓨터 구조를 정의하고 실제의 사용자 병렬 프로그램을 입력, 실행하여, 병렬 프로그램의 실제 출력을 얻음과 동시에, 설계한 가상 병렬 컴퓨터의 성능을 분석, 평가할 수 있다.

Chloramphenicol이 Mouse 십이지장 상피조직의 Alkaline Phosphatase 및 ??, ?? 활성에 미치는 영향

차상훈,이군자,이규식,정호삼 漢陽大學校 環境科學硏究所 1991 環境科學論文集 Vol.12 No.-

체중 20gm 내외의 ICR계 웅성 mouse에 체중 ㎏당 200㎎의 chloramphenicol을 매일 복강내로 주사한 후 희생전 12시간 동안 절식시키고 투여 제 5 일 및 제10일에 각각 희생시켜 십이지장을 적출하고 alkaline phosphatase 활성 및 ??, K?? 활성을 관찰하여 다음과 같은 결과를 얻었다. 1. Alkaline phosphatase 활성은 대조군 mouse 십이지장의 상피세포층에서는 강한 양성반응을 나타내었으나 chloramphenicol 5일 투여군에서는 중등도의 양성반응을 나타내었고 chloramphenicol 10일 투여군에서는 약한 양성반응을 나타내었다. 2. ??, ?? 활성은 대조군 mouse 십이지장의 상피세포층에서는 강한 양성반응을 나타내었으나 chloramphenicol 5일 투여군 및 chloramphenicol 10일 투여군에서는 모두 중등도의 양성반응을 나타내었다. 이상의 소견을 족합하면 chloramphenicol은 십이지장 상피세포에 손상을 야기시켜 상피세포의 기능을 저해하는 것으로 사료된다. Albino mice, ICR strain, weighing 20gm were used as experimental animals and chloramphenicol(20㎎/㎏) was administered to the experimental animals once a day for 10 days. The experimental animals were fasted 12 hours before sacrifice and ascrificed at 5 days and 10days after initial drug administration. For the evaluation of activities of ??, ?? and alkaline phosphatase the duodenal specimens were stained by Guth and Albert's method and Gomori's method, respectively. The results were as follows. 1. The activity of alkaline phosphatase in the epithelial layer of control mouse was strongly positive, while that of 5 days chloramphenicol treated mouse was moderately positive and that of 10 days chloramphenicol treated mouse was weakly positive. 2. The activity of ??, ?? in the epithelial layer of control mouse was strongly positive, while those of 5 days and 10 days chloramphenicol treated mouse was moderately positive. Consequently, it is suggested that chloramphenicol induce damages in the duodenal epithelium, so that it inhibits the function of the duodenal epithelium.