• Title/Summary/Keyword: oxidative metabolism

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Beneficial Effect of Epimedii Herba combined Samgijiwhang-Tang on Diabetic Nephropathy Rats (삼기지황탕가음양곽이 Streptozotocin으로 유발된 흰쥐의 당뇨병성(糖尿病性) 신증(腎症)에 미치는 영향)

  • Yoon Kwan-Hee;Kim Yong-Seong
    • The Journal of Korean Medicine
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    • v.27 no.1 s.65
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    • pp.47-56
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    • 2006
  • The present study was carried out to investigate the preventive effect of Epimedii Herba combined Samgijiwhang-Tang(SJTE) on streptozotocin(STZ)-induced diabetic nephropathy. SJTE was given to rats with oral administration. The experimental animals were divided into normal group of rats, control group of STZ-induced diabetic rats, and sample group with SJTE administration. Experimental diabetic nephropathy was induced by the injection of STZ(60mg/kg) to the rat via the peritoneum. The effect of SJTE on STZ-induced diabetic nephropathy was observed by measuring the serum level of insulin, glucose, creatinine and BUN. Urine secretion of albumin for 24 hours and urine level of glucose measures too. Anti-oxidative stress of STZ administration in living body was estimated by measuring lipid peroxide in cortex of kidneys. STZ induced increase of serum glucose. creatinine, urine albumin secretion and renal cortical lipid peroxidation were lowered by SJTE administration. In conclusion, the SJTE treatment showed protective effect on rat diabolic nephropathy model, and action mechanism of the effect was thought to be concerned with internal glucose metabolism.

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Enzyme Activities and Histochemical Changes in the Hind Limb Muscle of the Mouse Treated with 6-Aminonicotinamide

  • Kim Tai-Jeon;Bae Hyung-Joon;Kang Hee-Gyoo;Lee Dong-Beom
    • Biomedical Science Letters
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    • v.12 no.3
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    • pp.233-240
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    • 2006
  • We investigated enzyme activity and histochemical changes in hind limb of mouse treated with 6-aminonicotinamide (6-AN). The activity of aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase in 6-AN treated group were significantly higher than those of the control and pair-fed groups. Also, the activity of lactic dehydrogenase in 6-AN treated group was the highest among the three groups, whereas that of the pair-fed group were higher than that of the control group. In the 6-AN treated group, oxidative histochemical stains, nicotinamide adenine dinucleotide reductase (NADH), succinyl dehydrogenase (SDH) showed increased scattered fibers in 6-AN treated subsarcolemma. Cytochrome c oxidase (COX) stain showed decreased up to 85% in 6-AN treated fibers. These results demonstrate that 6-AN antagonizes cell metabolism and induces the morphological deformity like the other mitochondrial muscle diseases. Therefore, we suppose that these data would be useful indexes for disclosing the mechanism of mitochondrial muscle disease.

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Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic Opportunities

  • Jung, Byung-Jin;Yoo, Hwan-Sic;Shin, Sooyoung;Park, Young-Joon;Jeon, Sang-Min
    • Biomolecules & Therapeutics
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    • v.26 no.1
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    • pp.57-68
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    • 2018
  • Nuclear factor E2-related factor 2 (NRF2) plays an important role in redox metabolism and antioxidant defense. Under normal conditions, NRF2 proteins are maintained at very low levels because of their ubiquitination and proteasomal degradation via binding to the kelch-like ECH associated protein 1 (KEAP1)-E3 ubiquitin ligase complex. However, oxidative and/or electrophilic stresses disrupt the KEAP1-NRF2 interaction, which leads to the accumulation and transactivation of NRF2. During recent decades, a growing body of evidence suggests that NRF2 is frequently activated in many types of cancer by multiple mechanisms, including the genetic mutations in the KEAP1-NRF2 pathway. This suggested that NRF2 inhibition is a promising strategy for cancer therapy. Recently, several NRF2 inhibitors have been reported with anti-tumor efficacy. Here, we review the mechanisms whereby NRF2 is dysregulated in cancer and its contribution to the tumor development and radiochemoresistance. In addition, among the NRF2 inhibitors reported so far, we summarize and discuss repurposed NRF2 inhibitors with their potential mechanisms and provide new insights to develop selective NRF2 inhibitors.

Molecular Cloning and Characterization of Catechol 2, 3-Dioxygenase Gene from Aniline-Degrading Psseudomonas acidovorans

  • Lee, Ji-Hyun;Bang, Sung-Ho;Park, Youn-Keun;Lee, Yung-Nok
    • Korean Journal of Microbiology
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    • v.30 no.4
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    • pp.316-321
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    • 1992
  • Catechol 2, 3-dioxygenase (C230) catalyses the oxidative ring cleavage of catechol to 2-hydroxymuconic semialdehyde. This is one of the key reactions in the metabolism of the widespresd pollutant aniline. We have cloned a gene encoding C230 from cells of the aniline degrading bacteria, Pseudomonas acidovorance KCTC2494 strain and expressed in E. coli, A 11.3-kilobase Sau3A partial digested DNA fragment from KCTC2494 was cloned into phagemid vector pBluescript and designated as pLP201. The C230 gene was mapped to a 2.8-kb region, and the derection of transcription was determined. The cloned C230 gene contains its own promoter which can be recognized and employed by E. coli transcriptional apparatus. C230 activities of subclones were identified by enzyme assay and activity staining. The T7 RNA promoter/polymerase system and maxicell analysis showed that a polypeptide with Mw of 35 kDa is the C230 gene product.

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Antioxidant Effect of Bee Venom Herbal Acupuncture (봉독약침액의 항산화 효능)

  • Seo, Jung-Chul;Leem, Kang-Hyun;Han, Sang-Won
    • Journal of Pharmacopuncture
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    • v.6 no.1
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    • pp.67-72
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    • 2003
  • Bee venom has been clinically used to control the pain of inflammation disease etc. in general. Although the effect of bee venom herbal acupuncture has been reported, its mechanism has not been fully elucidated yet. Free radical metabolism seems to occupy a remarkably common position in the mechanisms of inflammation and ageing related disease. Oxidative damage to DNA, lipids, proteins and other molecules may contribute to the development inflammation disease. NO or DPPH is one of the free radicals and a mediator in inflammation diseases. The objective of this study is to investigate the scavenging effect of bee venom herbal acupuncture against NO and DPPH. The followings are the summary of the results: (1) There is no significant scavenging effect of bee venom herbal acupuncture on NO in BVS and BVP group. (2) There is a significant scavenging effect of bee venom herbal acupuncture on DPPH in BVS-1 and BVP-1 group. These results suggest that bee venom herbal acupuncture can be used for inflammation diseases such as rheumatoid arthritis. This study would provide important basic data on the possibility of the clinical treatment of bee venom herbal acupuncture. Further studies are required to investigate the antioxidative effects of it.

Study of Functional Verification to Abiotic Stress through Antioxidant Gene Transformation of Pyropia yezoensis (Bangiales, Rhodophyta) APX and MnSOD in Chlamydomonas

  • Lee, Hak-Jyung;Yang, Ho yeon;Choi, Jong-il
    • Journal of Microbiology and Biotechnology
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    • v.28 no.7
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    • pp.1217-1224
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    • 2018
  • Seaweeds produce antioxidants to counteract environmental stresses, and these antioxidant genes are regarded as important defense strategies for marine algae. In this study, the expression of Pyropia yezoensis (Bangiales, Rhodophyta) ascorbate peroxidase (PyAPX) and manganese-superoxide dismutase (PyMnSOD) was examined by qRT-PCR in P. yezoensis blades under abiotic stress conditions. Furthermore, the functional relevance of these genes was explored by overexpressing them in Chlamydomonas. A comparison of the different expression levels of PyAPX and PyMnSOD after exposure to each stress revealed that both genes were induced by high salt and UVB exposure, being increased approximately 3-fold after 12 h. The expression of the PyAPX and PyMnSOD genes also increased following exposure to $H_2O_2$. When these two genes were overexpressed in Chlamydomonas, the cells had a higher growth rate than control cells under conditions of hydrogen peroxide-induced oxidative stress, increased salinity, and UV exposure. These data suggest that Chlamydomonas is a suitable model for studying the function of stress genes, and that PyAPX and PyMnSOD genes are involved in the adaptation and defense against stresses that alter metabolism.

Study on Effect to Serotonin Metabolism of Gamiguibi-tang on P815 Cell (가미귀비탕(加味歸脾湯)이 P815세포의 serotonin 대사 과정에 미치는 영향)

  • No, Dong-Jin;Jung, In-Chul
    • Journal of Oriental Neuropsychiatry
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    • v.21 no.1
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    • pp.1-11
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    • 2010
  • Objectives: This study was perfomed to investigate the antioxidant activity and serotonin activity of Gami-guibi-tang on P815 Mast Cell. Methods: The effects of Gami-guibi-tang on activation of TPH-1 mRNA and AAADC mRNA in P815 mast cell were investigated. The effect of Gami-guibi-tang on content of serotonin in P815 mast cell was investigated. The effects of Gami-guibi-tang on activation of DPPH radical scavenging and SOD in P815 mast cell were investigated. Results: 1. The Gami-guibi-tang increased SOD activity and DPPH radical scavenging activity. 2. The Gami-guibi-tang increased the intracellular concentration of serotoninin 60 ${\mu}g/ml$, 80 ${\mu}g/ml$ experiment group. 3. The Gami-guibi-tang increased menaingful the manifestation TPH mRNA. 4. The manifestation of AAADC and MAO mRNA have not made menaingful changes on Gami-guibi-tang. Conclusions: This experiment shows that Gami-guibi-tang had significant anti-oxidative effect. And Gami-guibi-tang increased the intracellular concentration of serotonin. Therefore, Gami-guibi-tang can be used by the medication of major depression disorder. But Study on mechanism of increased serotonin and clinical research of Gami-guibi-tang is suggested for future research.

Induction of Lipin1 by ROS-Dependent SREBP-2 Activation

  • Seo, Kyuhwa;Shin, Sang Mi
    • Toxicological Research
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    • v.33 no.3
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    • pp.219-224
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    • 2017
  • Lipin1 was identified as a phosphatidate phosphatase enzyme, and it plays a key role in lipid metabolism. Since free radicals contribute to metabolic diseases in the liver, this study investigated the effects of free radicals on the regulation of Lipin1 expression in Huh7 and AML12 cells. Hydrogen peroxide induced mRNA and protein expression of Lipin1 in Huh7 cells, which was assayed by quantitative RT-PCR and immunoblotting, respectively. Induction of Lipin1 by hydrogen peroxide was confirmed in AML12 cells. Hydrogen peroxide treatment significantly increased expression of sterol regulatory element-binding protein (SREBP)-2, but not SREBP-1. Moreover, nuclear translocation of SREBP-2 was detected after hydrogen peroxide treatment. Hydrogen peroxide-induced Lipin1 or SREBP-2 expression was significantly reduced by N-acetyl-$\small{L}$-cysteine treatment, indicating that reactive oxygen species (ROS) were implicated in Lipin1 expression. Next, we investigated whether the hypoxic environments that cause endogenous ROS production in mitochondria in metabolic diseases affect the expression of Lipin1. Exposure to hypoxia also increased Lipin1 expression. In contrast, pretreatment with antioxidants attenuated hypoxia-induced Lipin1 expression. Collectively, our results show that ROS activate SREBP-2, which induces Lipin1 expression.

Autophagy in Ischemic Livers: A Critical Role of Sirtuin 1/Mitofusin 2 Axis in Autophagy Induction

  • Chun, Sung Kook;Go, Kristina;Yang, Ming-Jim;Zendejas, Ivan;Behrns, Kevin E.;Kim, Jae-Sung
    • Toxicological Research
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    • v.32 no.1
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    • pp.35-46
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    • 2016
  • No-flow ischemia occurs during cardiac arrest, hemorrhagic shock, liver resection and transplantation. Recovery of blood flow and normal physiological pH, however, irreversibly injures the liver and other tissues. Although the liver has the powerful machinery for mitochondrial quality control, a process called mitophagy, mitochondrial dysfunction and subsequent cell death occur after reperfusion. Growing evidence indicates that reperfusion impairs mitophagy, leading to mitochondrial dysfunction, defective oxidative phosphorylation, accumulation of toxic metabolites, energy loss and ultimately cell death. The importance of acetylation/deacetylation cycle in the mitochondria and mitophagy has recently gained attention. Emerging data suggest that sirtuins, enzymes deacetylating a variety of target proteins in cellular metabolism, survival and longevity, may also act as an autophagy modulator. This review highlights recent advances of our understanding of a mechanistic correlation between sirtuin 1, mitophagy and ischemic liver injury.

Hydrogen Peroxide Induces Apoptosis of BJAB Cells Due to Formation of Hydroxyl Radicals Via Intracellular Iron-mediated Fenton Chemistry in Glucose Oxidase-mediated Oxidative Stress

  • Lee, Jeong-Chae;Son, Young-Ok;Choi, Ki-Choon;Jang, Yong-Suk
    • Molecules and Cells
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    • v.22 no.1
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    • pp.21-29
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    • 2006
  • The aim of this study was to determine if hydrogen peroxide ($H_2O_2$) generated by glucose oxidase (GO) induces apoptosis or necrosis of BJAB cells and which radical is the direct mediator of cell death. We found that GO produced $H_2O_2$ continuously in low concentrations, similar to in vivo conditions, and decreased proliferation and cell viability in a dose-dependent manner. The GO-mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the cells after H33342/Annexin V/propidium iodide staining. Decreases of mitochondrial membrane potential and intracellular glutathione level were found to be critical events in the $H_2O_2$-mediated apoptosis. Additional experiments revealed that $H_2O_2$ exerted its apoptotic action through the formation of hydroxyl radicals via the Fenton rather than the Haber-Weiss reaction. Moreover, intracellular redox-active iron, but not copper, participated in the $H_2O_2$-mediated apoptosis.