• Title/Summary/Keyword: iNOS synthesis

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Catalase protects cardiomyocytes via its inhibition of nitric oxide synthesis

  • Chae, Han-Jung;Chae, Soo-Wan;Kim, Hyung-Ryong
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.80.3-81
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    • 2003
  • Nitric oxide (NO) has been reported to play an important role as an effector molecule in cytokine signal transduction in cardiomyocytes. The treatment of IL-1b/ TNF-a (2 ng/ml)/ IFN-g (50 U/ml) induced apoptosis in neonatal rat ventricular cardiomyocytes via NO-dependent pathway. When cardiomyocytes were treated with IL-1b (20 ng/ml)/TNF-a (2 ng/ml)/ IFN-g(50 U/ml) in the presence of catalase, the cells were much more resisant to the cell death as well as NO synthesis. However, catalase significantly enhanced the expression of iNOS protein in cardiomyocytes. (omitted)

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Interrelation between Expression of ADAM 10 and MMP 9 and Synthesis of Peroxynitrite in Doxorubicin Induced Cardiomyopathy

  • Lim, Sung Cil
    • Biomolecules & Therapeutics
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    • v.21 no.5
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    • pp.371-380
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    • 2013
  • Doxorubicin is still main drug in chemotherapy with limitation of use due to adverse drug reaction. Increased oxidative stress and alteration of nitric oxide control have been involved in cardiotoxicity of doxorubicin (DOX). A Disintegrin And Metalloproteinase (ADAMs) are transmembrane ectoproteases to regulate cell-cell and cell-matrix interactions, but role in cardiac disease is unclear. The aim of this study was to determine whether DOX activates peroxynitrite and ADAM 10 and thus ADAM and matrix metalloproteinase (MMP) induce cardiac remodeling in DOX-induced cardiomyopathy. Adult male Sprague-Dawley rats were subjected to cardiomyopathy by DOX (6 times of 2.5 mg/kg DOX over 2-weeks), and were randomized as four groups. Then followed by 3, 5, 7, and 14 days after cessation of DOX injection. DOX-injected animals significantly decreased left ventricular fractional shortening compared with control by M-mode echocardiography. The expressions of cardiac nitrotyrosine by immunohistochemistry were significant increased, and persisted for 2 weeks following the last injection. The expression of eNOS was increased by 1.9 times (p<0.05), and iNOS was marked increased in DOX-heart compared with control (p<0.001). Compared to control rats, cardiac ADAM10- and MMP 9- protein expressions increased by 20 times, and active/total MMP 9 proteolytic activity showed increase tendency at day 14 after cessation of DOX injection (n=10, each group). DOX-treated $H_9C_2$ cell showed increased ADAM10 protein expression with dose-dependency (p<0.01) and morphometric changes showed the increase of ventricular interstitial, nonvascular collagen deposition. These data suggest that activation of cardiac peroxynitrite with increased iNOS expression and ADAM 10-dependent MMP 9 expression may be a molecular mechanism that contributes to left ventricular remodeling in DOXinduced cardiomyopathy.

Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-κB in LPS-stimulated RAW264.7 cells and mouse liver

  • Kim, Dae Hyun;Chung, Jae Heun;Yoon, Ji Sung;Ha, Young Mi;Bae, Sungjin;Lee, Eun Kyeong;Jung, Kyung Jin;Kim, Min Sun;Kim, You Jung;Kim, Mi Kyung;Chung, Hae Young
    • Journal of Ginseng Research
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    • v.37 no.1
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    • pp.54-63
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    • 2013
  • Ginsenoside Rd is a primary constituent of the ginseng rhizome and has been shown to participate in the regulation of diabetes and in tumor formation. Reports also show that ginsenoside Rd exerts anti-oxidative effects by activating anti-oxidant enzymes. Treatment with ginsenoside Rd decreased nitric oxide and prostaglandin $E_2$ ($PGE_2$) in lipopolysaccharides (LPS)-challenged RAW264.7 cells and in ICR mouse livers (5 mg/kg LPS; LPS + ginsenoside Rd [2, 10, and 50 mg/kg]). Furthermore, these decreases were associated with the down-regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 and of nuclear factor (NF)-${\kappa}B$ activity in vitro and in vivo. Our results indicate that ginsenoside Rd treatment decreases; 1) nitric oxide production (40% inhibition); 2) $PGE_2$ synthesis (69% to 93% inhibition); 3) NF-${\kappa}B$ activity; and 4) the NF-${\kappa}B$-regulated expressions of iNOS and COX-2. Taken together, our results suggest that the anti-inflammatory effects of ginsenoside Rd are due to the down-regulation of NF-${\kappa}B$ and the consequent expressional suppressions of iNOS and COX-2.

High molecular weight water-soluble chitosan acts as an accelerator of macrophages activation by recombinant interferon ${\gamma}$ via a process involving $_L$-arginine -dependent nitric oxide production

  • Kim, Hyung-Min
    • Advances in Traditional Medicine
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    • v.1 no.1
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    • pp.71-81
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    • 2000
  • High molecular weight water-insoluble chitosan alone has been previously shown to exhibit in vitro stimulatory effect on macrophages nitric oxide (NO) production. However, high molecular weight water-soluble chitosan (WSC) had no effect on NO production by itself. When WSC was used in combination with recombinant $interferon-{\gamma}\;(Rifn-{\gamma})$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of WSC on NO synthesis was shown at 24 h after treatment with $rIFN-{\gamma}$. The increased production of NO from $rIFN-{\gamma}$ plus WSC-stimulated RAW 264.7 macrophages was decreased by the treatment with $N^G$ $monomethyl-_L-arginine$. The increase in NO synthesis was reflected, as an increased amounts of inducible NO synthase (iNOS) protein. Synergy between $rIFN-{\gamma}$ and WSC was mainly dependent on WSC-induced nuclear $factor-_KB$ activation. The present results indicate that WSC may provide various activities such as anti-microbial, anti-tumoral, and anti-viral. In addition, since NO has emerged as an important intracellular and intercellular regulatory molecule having functions as diverse as vasodilation, neural communication, cell growth regulation and host defense, it is tempting to hypothesize that this WSC is involved in the local control of the various fundamental processes such as cardiagra, cardiac infarction, impotence etc.

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Enhancing the Effect of Aronia Extract on Hyaluronic Acid Synthesis through Liposome Formation

  • Youn, Young Han
    • Journal of People, Plants, and Environment
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    • v.23 no.4
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    • pp.465-473
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    • 2020
  • Background and objective: Aronia melanocarpa, called black chokeberry, is a natural product belonging to the family rosaceae, and is known to contain polyphenolic antioxidants including cyanidin-3-galactoside, cyanidin-3-arabinoside, cyanidin-3-xyloside, and cyanidin-3-glucoside Because of the abundance of anthocyanins, Aronia has been studied to be used in various industries. Methods: Aronia melanocarpa extract was treated 24 hours a day to RAW 264.7 cells with inflammations induced by LPS. After extracting total RNA, the amount of inflammatory cytokine expression was measured using RT-PCR. After processing the Aronia liposome using Aronia extract and the layer-by-layer electrostatic deposition method in keratinocyte cells at the same time, we checked the synthesis of Hyaluronic acid enhanced through the formation of Aronia liposome using ELISA. Results: The treatment of Aronia extract in inflammation-induced RAW 264.7 cells conducted to check the anti-inflammatory efficacy of Aronia extract inhibited inflammatory cytokines including TLR4, TNF-α, IL-1β, COX-2, and iNOS and increased the mRNA expression of HAS2 genes related to moisturizing. Based on the anti-inflammatory and moisturizing effect of Aronia extract, the Aronia liposome technology was introduced to Aronia extract to produce Aronia liposome. Conclusion: The liposome formation of Aronia extract is expected to be used as a functional material in treating various inflammatory skin diseases by controlling the moisture content of the corneocytes by increasing the expression rate of genes associated with the synthesis of hyaluronic acid, while retaining the efficacy of its components.

Inhibitory Effect of Chan-Su on the Secretion of PGE2 and NO in LPS-stimulated BV2 Microglial Cells

  • Kim, Min-Hee;Lyu, Ji-Hyo;Lyu, Sun-Ae;Hong, Sang-Hoon;Kim, Won-Il;Yoon, Hwa-Jung;Ko, Woo-Shin
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.5
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    • pp.1315-1321
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    • 2008
  • Chan-Su (Venenum bufonis) has long been for a variety of other purposes including treatment of inflammation in the folk medicine recipe. Since nitric oxide (NO) is one of the major inflammatory parameters, we first studied the effects of Chan-Su on NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, Chan-Su inhibited the secretion of NO in BV2 microglial cells, without affecting cell viability, The protein level of inducible nitric oxide synthase (iNOS) was decreased by Chan-Su, And Chan-Su also inhibited production of prostaglandin E2 (PGE2) and expression of cyclooxygenase (COX)-2. Proinflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$ and IL-12, were inhibited by Chan-Su in a dose-dependent manner. And Chan-Su inhibited the degradation of ${IkB-\alpha}$, which was considered to be inhibitor of nuclear factor $(NF)-{\kappa}B$, one of a potential transcription factor for the expression of iNOS, COX-2 and proinflammatory cytokines. These results suggest that Chan-Su could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of $I{\kappa}B-{\alpha}$ degradation.

Anti-inflammatory Activities Verification of Vaccinum oldhami Fruit Ethanol Extracts on RAW 264.7 (RAW 264.7을 이용한 정금나무 열매(Vaccinum oldhami fruit)의 항염증 효과)

  • Lee, Jin-Young;Joo, Da-Hye;Yoo, Dan-Hee;Chae, Jung-Woo
    • Journal of Life Science
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    • v.27 no.4
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    • pp.417-422
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    • 2017
  • The purpose of this study was to investigate the role of the Vaccinum oldhami fruit extract as a cosmetic additive. As a result of having macrophage (RAW 264.7) measured a cell toxicity effects of 70% ethanol extract from Vaccinum oldhami fruit, it shown 118% with toxicity at $500{\mu}g/ml$ concentration. In nitric oxide synthesis inhibition effect, 70% ethanol extracts from Vaccinum oldhami fruit shown 47.3% at $1,000{\mu}g/ml$ concentration. The iNOS, COX-2 protein expression inhibitory effect by western blot of 70% ethanol extract from Vaccinum oldhami fruit was decreased by 36.13%, 29.61% at $500{\mu}g/ml$ concentration. And iNOS, COX-2 mRNA expression inhibitory effect by reverse-transcription-PCR of 70% ethanol extract from Vaccinum oldhami fruit was decreased by 62.25%, 90.07% at $500{\mu}g/ml$ concentration. All these finding that extract from Vaccinum oldhami fruit could prove that their have effects anti-inflammatory efficacy. And extract from Vaccinum oldhami fruit has potential as a cosmetic ingredients.

NITRIC OXIDE AND DENTAL PULP (NITRIC OXIDE와 치수)

  • Kim, Young-Kyung;Kim, Sung-Kyo
    • Restorative Dentistry and Endodontics
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    • v.27 no.5
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    • pp.543-551
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    • 2002
  • Nitric oxide (NO) is a small molecule (mol. wt. 30 Da) and oxidative free radical. It is uncharged and can therefore diffuse freely within and between cells across membrane. Such characteristics make it a biologically important messenger in physiologic processes such as neurotransmission and the control of vascular tone. NO is also highly toxic and is known to acts as a mediator of cytotoxicity during host defense. NO is synthesized by nitric oxide synthase (NOS) through L-arginine/nitric oxide pathway which is a dioxygenation process. NO synthesis involves several participants, three co-substrates, five electrons, five co-factors and two prosthetic groups. Under normal condition, low levels of NO are synthesized by type I and III NOS for a short period of time and mediates many physiologic processes. Under condition of oxidant stress, high levels of NO are synthesized by type II NOS and inhibits a variety of metabolic processes and can also cause direct damage to DNA. Such interaction result in cytostasis, energy depletion and ultimately cell death. NO has the potential to interact with a variety of intercellular targets producing diverse array of metabolic effects. It is known that NO is involved in hemodynamic regulation, neurogenic inflammation, re-innervation, management of dentin hypersensitivity on teeth. Under basal condition of pulpal blood flow, NO provides constant vasodilator tone acting against sympathetic vasoconstriction. Substance P, a well known vasodilator, was reported to be mediated partly by NO, while calcitonin-gene related peptide has provided no evidence of its relation with NO. This review describes the roles of NO in dental pulp in addition to the known general roles of it.

Experimental Study of Yongdamsagantang on the Anti-viral Activity and Immune Response to Mice (龍膽瀉肝湯의 抗바이러스 活性 및 免疫反應에 對한 實驗的 考察)

  • Kim, Nam-Kwen;Kim, Jong-han;Lim, Gyu-sang;Hwang, Choong-yeon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.11 no.1
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    • pp.1-22
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    • 1998
  • During the last few years, nitric oxide(NO) as a potent macrophage-derived effector molecule against a variety of bacteria, parasites, and tumors has received increasing attention. More recent studies suggest that NO also has antiviral effects in both murine and human cells. The objective of the current study was to determine the effect of Yongdamsagantang(YST) on the production of NO. Stimulation of mouse peritoneal macrophages with YST after the treatment of recombinant $interferon-{\gammer}(rlFN-{\gammer})$ resulted in the increased NO synthesis. YST had no effect on NO synthesis by itself. When YST was used in combination with $rIFN-{\gammer}$, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of YST on NO synthesis was shown 6 hour after treatment with $rIFN-{\gammer}$. This increase in NO synthesis was reflected as increased amount of inducible NO synthase(iNOS) protein. NO production was inhibited by $N^G-monomethyl-L-arginine$. The increased production of NO from $rIFN-{\gammer}$ plus YST-stimulated cells was decreased by the treatment with staurosporin. In addition, synergy between $rIFN-{\gammer}$ and YST was mainly dependent on YST-induced tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ secretion. These results suggest that the capacity of YST to increase NO production from $rIFN-{\alpha}-primed$ mouse peritoneal macrophages is the result of YST-induced $TNF-{\alpha}$ secretion.

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Effect of Glutathione on Lead Induced Modulation of NO Synthesis in RAW 264.7 Cell (RAW 264.7 Cell에서 납에 의한 NO 생성의 조절에 미치는 Glutathione의 효과)

  • Oh, Gyung-Jae;Kwon, Keun-Sang;Yoon, Wook-Hee;Shin, Sae-Ron
    • Journal of Preventive Medicine and Public Health
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    • v.35 no.4
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    • pp.269-274
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    • 2002
  • Objectives : To evaluate the elect of glutathione(GSH) on lead induced modulation of nitric oxide(NO) synthesis, and to examine how lead modulates NO production in macrophages. Methods : This study was observed in a culture of RAW 264.7 cells, which originated from a tumor in a Balb/c mouse that was induced by the Abelson murine leukemia virus. The compounds investigated were lead chloride, N-acetyl-cystein(NAC), and Buthionine Sulfoximine( BSO). Results : ATP synthesis in RAW 264.7 cells was unchanged by each lead concentration exposure in a dose dependent manner. The NO synthesis was decreased when exposed to lead($PbCl_2$) concentration $0.5{\mu}M$. The presence of $300{\mu}M$ NAC, used as a pretreatment in the culture medium, caused the recovery of the lead induced decrease in NO synthesis, but in the presence of $300{\mu}M$ BSO as a pretreatment, there was no recoverey. Pretreatment with NAC and BSO had no affect on ATP synthesis at any of the lead concentrations used. Conclusions : These results indicated that GSH has a protective effect toward lead toxicity, and suggested that the inhibition of NO production in macrophage due to lead toxicity may be related to cofactors of iNOS (inducible nitric oxide synthase)