• Title/Summary/Keyword: nad1/2-3

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The Relationship between Mitochondria and NLRP3 Inflammasome

  • Lee, Hyun Ah;Na, Hee Sam;Chung, Jin
    • International Journal of Oral Biology
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    • v.42 no.3
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    • pp.85-90
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    • 2017
  • Mitochondria participate in various intracellular metabolic pathways such as generating intracellular ATP, synthesizing several essential molecules, regulating calcium homeostasis, and producing the cell's reactive oxygen species (ROS). Emerging studies have demonstrated newly discovered roles of mitochondria, which participate in the regulation of innate immune responses by modulating NLRP3 inflammasomes. Here, we review the recently proposed pathways to be involved in mitochondria-mediated regulation of inflammasome activation and inflammation: 1) mitochondrial ROS, 2) calcium mobilization, 3) nicotinamide adenine dinucleotide ($NAD^+$) reduction, 4) cardiolipin, 5) mitofusin, 6) mitochondrial DNA, 7) mitochondrial antiviral signaling protein. Furthermore, we highlight the significance of mitophagy as a negative regulator of mitochondrial damage and NLRP3 inflammasome activation, as potentially helpful therapeutic approaches which could potentially address uncontrolled inflammation.

Mechanism of Action of Anticancer Drug Aziridinylbenzoquinones: Involvement of DT-diaphorase (DNA에 결합하는 항암제의 작용기전)

  • Lee, Chong-Soon-
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.11a
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    • pp.147-172
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    • 1994
  • Aziridinylbenzoquinones such as 3, 6-diaziridinyl-1, 4-benzoquinone (DZQ) and its 2, 5-methyl analog (MeDZQ) require bioreductive activation in order to elicit their anticancer activities. To determine the involvement of DTD in the activation of these drugs, we have used a ligation-mediated polymerase chain reaction to map the intracellular alkylation sites in a sing1e copy gene at the nucleotide level. We have performed this analysis in two human colon carcinoma cells, one proficient (HT-29) and one deficient (BE) in DT-diaphorase (DTD) activity. In the DTD proficient HT-29 cell line, DZQ and MeDZQ were found to alkylate both 5'-(A/T)G(C)-3' and 5'-(A/T)A-3' sequences. This is consistent with the nucleotide preferences observed when DZQ and MeDZQ are activated by purified DTD to reactive metabolites capable of alkylating DNA in vitro [Lee, C. -S., Hartley, J. A., Berardini, M. D., Butler, J., Siegel., D., Ross, D., & Gibson, N. W. (1992) Biochemistry, 31: 3019-3025]. Surprisingly in the DTD-deficient BE cell line a pattern of alkylation induced by DZQ and MeDZQ similar to that observed in the DTD-proficient HT-29 cells was observed. This suggests that reductive enzymes other than DTD can be involved in activating DZQ and MeDZQ to DNA reactive species in vivo.

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The Role of Poly(ADP-ribose) Polymerase-1 in Ventilator-Induced Lung Injury (기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할)

  • Kim, Je-Hyeong;Yoon, Dae Wui;Hur, Gyu Young;Jung, Ki Hwan;Lee, Sung Yong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Yoo, Se Hwa;Kang, Kyung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.451-463
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    • 2006
  • Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

Physiological and Molecular Characterization of NAD(P)H-Nitroreductase from Stenotrophomonas sp. OK-5 (Stenotrophomonas sp. OK-5에서 분리한 NAD(P)H-Nitroreductase의 생리학적 및 분자생학적 특성 연구)

  • Ho Eun-Mi;Kahng Hyung-Yeel;Oh Kye-Heon
    • Korean Journal of Microbiology
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    • v.40 no.3
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    • pp.183-188
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    • 2004
  • Stenotrophomonas sp. OK-5 capable of degrading TNT has been found to have three nitroreductase fractions designated as NTR fractions I, II, and III. NTR in a previous study. This study was attempted to reveal physiological and molecular characteristics of NTR fractions I, II, and III in strain OK-5. Several chemicals (e.g., EDTA, NaCl, dithiothreitol, $\beta$-mercaptoethanol) were tested for their effect on enzyme activity of NTRs, demonstrating that enzyme activities of NTR fractions I, II, and III from OK-5 were inhibited in the presence of $\beta$-mercaptoethanol. Substrate specificity test showed that NTR fractions I, II, and III all have over 70% enzyme activities for nitrobenzene or RDX as a substrate. N-terminal amino acid sequence of NTR fraction I from Stenotrophomonas sp. OK-5 was $^1MSDLLNADAVVQLFRTARDS^20$ and exhibited 70% sequence homology with that of NTR from Xanthomonas campestris. NTR I gene from Stenotrophomonas sp. OK-5 (SmOK5nrI) shared extensive sequence homology in deduced amino acid sequence of PCR product with NTRs from Xanthomonas campestris (81 %), X. axonopodis (75%), Streptomyces avermitilis(30%), whereas they had low homology with that from P. putida KT2440 (pnrB) (16%).

Two Human Cases of Echinococcus ortleppi Infection in the Lung and Heart in Vietnam

  • De, Nguyen Van;Minh, Pham Ngoc;Duyet, Le Van;Bich, Nguyen Ngoc;Son, Trinh Nam;Jung, Bong-Kwang;Chai, Jong-Yil
    • Parasites, Hosts and Diseases
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    • v.58 no.4
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    • pp.451-456
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    • 2020
  • This is a report of 2 cases of human hydatidosis caused by Echinococcus ortleppi in Vietnam. The patients were a 12-year-old male (case 1) having a cyst of 10.0×9.0 cm size in the lung and a 50-year-old female with a 3.0×3.3 cm-sized cyst in the heart. Eosinophilia was 33.7% in the male and 45.8% in the female patient. C-reactive protein was increased to 16.5 mg/L in the male and 18.2 mg/L in the female. Both patients were positive for ELISA at OD=2.5 and 3.1, respectively. Echinococcus protoscolices were collected from the cysts by amniocentesis and surgery. The protoscolices were identified as E. ortleppi by morphology and analysis of mitochondrial NADH dehydrogenase 1 (nad1) gene sequence. Both patients were cured by surgical resection of the hydatid cyst combined with albendazole medication. The E. ortleppi infection in lung is the second report, and the other in the heart is the first in Vietnam.

Study on the Manufacturing techniques & Conservation of Iron Pot from Cheonmachong Ancient Tomb (천마총 출토 철부(鐵釜)의 제작기법 및 보존처리)

  • Lee, Seung Ryul;Shin, Yong Bi;Jung, Won Seob
    • Journal of Conservation Science
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    • v.30 no.3
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    • pp.263-275
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    • 2014
  • It's shown how to proceed the study on Manufacturing techniques & Conservation to the Iron Pot from Cheonmachong Ancient Tomb(the 155th Tomb in Hwangnam-dong). In order to investigate manufacturing techniques of the Iron Pot, some parts of the relic were gathered. After mounting, polishing and etching on the relic, analyzing the metal microstructure was conducted. Also it's conducted a SEM-EDS analysis on the nonmetallic inclusion. White iron structure was observed in the metallurgical structure inspection, SEM-EDS analysis. It seems to be dried slowly at room temperature after casting, doesn't look as particular heat treatment to improve brittleness. It is estimated that it's as the handle seam side were verified about 3cm inch wide, 1.5 thick in center of body, so 2 separate half-completed products was cast with width-type mould. The manufacturing techniques Using white cast iron structure, width-type mould are observable to the Iron Pot excavated from Sikrichong Ancient Tomb & Hwangnamdaechong grand Ancient Tomb around those were constructed the same time. It's able to recognize that it's almost identical manufacturing techniques at that time. Conservation is generically following those are survey of pretreatment, foreign material removal, stabilization, restoration and color matching in the order. cleaning & drying were added to the process as occasion demands. The strengthening treatment were difficult with artifact's volume, low concentration Paraloid NAD-10 solution was spread two or three times with a brush, surface hardening also came up with 15wt% Paraloid NAD-10 solution after the conservation was complete. There were connection & restoration for the restoration to the damage after modeling forms that it's similar to damaged parts by using the Fiber Reinforced Plastic resins(POLYCOAT FH-245, mold laminated type). Throughout this research, capitalizing on accumulations of measurements about the production technique of Iron Pot in the time of the fifth and 6th centuries is no less important than the Iron artifact's conservation for a better study in the future.

Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice

  • Lee, Heaji;Lim, Yunsook
    • Nutrition Research and Practice
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    • v.13 no.5
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    • pp.377-383
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    • 2019
  • BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ${\geq}250mg/dL$), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear $factor-{\kappa}B$ pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

Studies on amylase producing bacteria and its stimulaton. (I) (Amylase 생산세균 및 생산능의 촉진조건에 관한 연구 1)

  • 이두영
    • Korean Journal of Microbiology
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    • v.7 no.2
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    • pp.86-90
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    • 1969
  • 1. Amylase producing bacteria have been isolated from natural sources and was identified out. The above strain is identical to Bacillus subtillis in every details of physiological and morphorogical characteristics by this investigations. 2. Sikworm chrysalis nad chlorella extracts are prove to be further effective for the stimulation of amylase production than any other sources. The former silkworm extract is more stronger in its activity. 3. It is found that effective results had been accepted by a less soybean meal addition per that of wheat bran in the mixture ratio of them, also less addition of corn is needed in the mixture ratio of between corn and whear bran. In the mixing ratio of wheat bran per silkworm or chlorella extracts, the addition of wheat bran is necessary for stimulation of amylase production. 4. Fro the stimulation of amylase production, the effective substances from natural sources and its order of activity in cultral media cultral media is proved as follows, silkworms ext.>chlorella ext.>alcohol>skim-milk and peptone>fermented milk>radish leaf ext.

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Studies on the Chung-Kook-Jang Fermcntation (I) (청국장제조에 관한 연구 1)

  • 박계인;성현순
    • Korean Journal of Microbiology
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    • v.9 no.2
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    • pp.74-85
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    • 1971
  • A study was carried out to investigate the bacteria during the Chung-Kook-Jang fermentation. The results were summarized as follows ; 1) The bacteria were isolated total 65 strains from the Natrual Chung-Kook-Jang fermentation in $37^{\circ}C$ incubator ; 37 strains from sample K with rise straw and 28 strains from sample steamed soy bean only. 2) In first screening, 15 strains were selected by super protease among them ; 8 strains from K and 7 strains from S. 3) In second screening, No. K-27 and No.S-16 were selected as the best strains for the Chung Kook-Jang fermentation. by panel-test among the first screenings. 4) No. K-27 and No. S-16, the selected best strains were classified nad identified as variation of Bacillus subtilis by Bergey's manual.

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Notoginseng leaf triterpenes ameliorates mitochondrial oxidative injury via the NAMPT-SIRT1/2/3 signaling pathways in cerebral ischemic model rats

  • Weijie, Xie;Ting, Zhu;Ping, Zhou;Huibo, Xu;Xiangbao, Meng;Tao, Ding;Fengwei, Nan;Guibo, Sun;Xiaobo, Sun
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.199-209
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    • 2023
  • Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.