• Title, Summary, Keyword: iNOS

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Nitric Oxide Synthase Expressions in ADR-induced Cardiomyopathy in Rats

  • Liu, Baogang;Li, Hongli;Qu, Hongyan;Sun, Baogui
    • BMB Reports
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    • v.39 no.6
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    • pp.759-765
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    • 2006
  • In this study, we investigate Nitric oxide synthase (NOS) expressions in adriamycin (ADR)-induced cadiomyopathy in rats. Sixty male Wistar rats were randomly divided into two main groups: control and ADR groups. Myocardial histopathological observation was performed; Expressions of 3 isoforms of NOS genes were examined by RT-PCR analysis; Expressions of 3 isoforms of NOS protein was assessed by Western blot analysis. Myocardium exhibited intensive morphological changes after 8 weeks of ADR treatment. The expression levels of inducible NOS (iNOS) gene and protein were significantly increased in ADR-treated rats after 8 weeks of treatment and then slightly increased at weeks 9 and 10. No significantly difference of neuronal NOS (nNOS) or endothelial NOS (eNOS) gene and protein were observed in the myocardium obtained from the control rats and ADR-injected rats at any time point. iNOS gene expression is selectively induced by ADR in heart. The upregulation of iNOS gene and protein may be somehow correlated with morphological changes seen in heart of rat treated with ADR.

Effects of Semen jugrandis on the iNOS Expression and Superoxide Formation in the RAW264.7 Cells (호도(胡挑) 추출물이 마우스 대식세포주인 RAW264.7 세포주의 iNOS 발현 및 Superoxide 형성에 미치는 영향)

  • Moon, Goo;Ko, Su-Mi
    • The Journal of Korean Medicine
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    • v.20 no.1
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    • pp.151-160
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    • 1999
  • Nitric oxide(NO) is synthesized via the oxidation of L-arginine by a family of nitric oxide synthases(NOS), which are either constitutive(cNOS) or inducible(iNOS). The induction of iNOS in tissues can lead to the sustained production of high concentrations of NO which may exert pro-inflammatory effects including vasodilation. edema, cyototoxicity, and its activity can be mediated by various pro-inflammatory cytokine, including interferon ${\gamma}(INF-{\gamma})$. tumor necrosis factor, IL- 1 and IL-6. The enzyme, iNOS, became a new target for pharmacologcal research with the aim to find new substances for the treatment of chronic inflammatory disorders. Murine macrophages produce large amounts of NO when activated with $TFN-{\gamma}$ plus LPS. The murine macrophage-like cell line, RAW 264.7, is a suitable cell model on which to perform vitro studies regarding the iNOS system. Semen jugrandis is a fatty walnut seed found in Korea. The walnut have been used in foik medicine to improve virility, to relieved asthma, and to relieve constipation. Sesquiterpenelactones were isolated from this plant. In the course of screening for NO inhibitory activity from medicnial plants, the aqueous extract of this plant was found to have a significant activity. The result are summarized as followings. 1. The viability of cells incubated in the presence of semen jugrandis increased mare than non incubated cells. 2. Semen jugrandis suppressed the production of NO in tissues dependent on density. 3. Semen jugrandis suppressed the induction of iNOS in tissues dependent on density can lead to reduced production of NO. 4. Semen jugrandis suppressed the production of superoxide in tissue depend on density. According to the above mentioned results, semen jugrandis could be applied production of NO and superoxide can lead to reduction of chronic inflammatary. And as a depence matter come into a virus of microbe and tumor cells.

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NFATc Mediates Lipopolysaccharide and Nicotine-Induced Expression of iNOS and COX-2 in Human Periodontal Ligament Cells (사람 치주인대세포에서 Lipopolysaccharide와 니코틴으로 유도된 iNOS와 COX-2 발현에 NFATc의 관여)

  • Lee, Sang-Im;Yu, Ji-Su
    • Journal of dental hygiene science
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    • v.15 no.6
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    • pp.753-760
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    • 2015
  • Although nuclear factor of activated T cell (NFAT) plays a key role in inflammation, its anti-inflammatory effects and mechanism of action in periodontitis are still unknown. This study aimed to identify the effects of NFAT on the proinflammatory mediators activated by lipopolysaccharide (LPS) plus nicotine stimulation in human periodontal ligament cells (hPDLCs). The production of nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ was evaluated using Griess reagent and an enzyme immunoassay, respectively. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and NFAT proteins was evaluated by Western blot analysis. LPS plus nicotine synergistically induced the production of NO and $PGE_2$ and increased the protein expression of iNOS, COX-2 and NFAT. Treatment with an NFAT inhibitor blocked the LPS plus nicotine-stimulated NO and $PGE_2$ release as well as the expression of iNOS and COX-2. Our data suggest that the LPS plus nicotine-induced inflammatory effects on hPDLCs may act through a novel mechanism involving the action of NFAT. Thus, NFAT may provide a potential therapeutic target for the treatment of periodontal disease associated with smoking and dental plaque.

Lipopolysaccharide Inhibits Proliferation of the Cultured Vascular Smooth Muscle Cells by Stimulating Inducible Nitric Oxide Synthase and Subsequent Activation of Guanylate Cyclase

  • Choi, Hyoung-Chul;Lee, Sang-Gon;Kim, Jong-Ho;Kim, Joo-Young;Sohn, Uy-Dong;Ha, Jeoung-Hee;Lee, Kwang-Youn;Kim, Won-Joon
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.4
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    • pp.343-351
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    • 2001
  • This study was undertaken to investigate the mechanism of lipopolysaccharide (LPS) and nitric oxide (NO) as a regulator of vascular smooth muscle cell (VSMC) proliferation. VSMC was primarily cultured from rat aorta and confirmed by the immunocytochemistry with anti-smooth muscle myosin antibody. The number of viable VSMCs were counted, and lactate dehydrogenase (LDH) activity was measured to assess the degree of cell death. Concentrations of nitrite in the culture medium were measured as an indicator of NO production. LPS was introduced into the medium to induce the inducible nitric oxide synthase (iNOS) in VSMC, and Western blot for iNOS protein and RT-PCR for iNOS mRNA were performed to confirm the presence of iNOS. Inhibitors of iNOS and soluble guanylate cyclase (sGC), sodium nitroprusside (SNP) and L-arginine were employed to observe the action of LPS on the iNOS-NO-cGMP signalling pathway. LPS and SNP decreased number of VSMCs and increased the nitrite concentration in the culture medium, but there was no significant change in LDH activity. A cell permeable cGMP derivative, 8-Bromo-cGMP, decreased the number of VSMCs with no significant change in LDH activity. L-arginine, an NO substrate, alone tended to reduce cell count without affecting nitrite concentration or LDH level. Aminoguanidine, an iNOS specific inhibitor, inhibited LPS-induced reduction of cell numbers and reduced the nitrite concentration in the culture medium. LY 83583, a guanylate cyclase inhibitor, suppressed the inhibitory actions of LPS and SNP on VSMC proliferation. LPS increased amounts of iNOS protein and iNOS mRNA in a concentration-dependent manner. These results suggest that LPS inhibits the VSMC proliferation via production of NO by inducing iNOS gene expression. The cGMP which is produced by subsequent activation of guanylate cyclase would be a major mediator in the inhibitory action of iNOS-NO signalling on VSMC proliferation.

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Nitric Oxide Prevents the Bovine Cerebral Endothelial Cell Death Induced by Serum-Deprivation

  • Kim, Chul-Hoon;Ahn, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.5
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    • pp.515-521
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    • 1997
  • Endothelial cells play a central role in the inflammatory processes, and activation of nuclear factor kappa B ($NF-_{\kappa}B$) is a key component in that inflammatory processes. Previously, we reported that tumor necrosis factor alpha($TNF{\alpha}$) had protective effect of cell death induced by serum deprivation and this protection was related to $NF-_{\kappa}B$ activation. Inducible nitric oxide synthase (iNOS) is a member of the molecules which transcription is regulated mainly by $NF-_{\kappa}B$. And the role of nitric oxide (NO) generated by iNOS on cell viability is still controversial. To elucidate the mechanism of $TNF{\alpha}$ and $NF-_{\kappa}B$ activation on cell death protection, we investigate the effect of NO on the cell death induced by serum- deprivation in bovine cerebral endothelial cells in this study. Addition of $TNF{\alpha}$, which are inducer of iNOS, prevented serum-deprivation induced cell death. Increased expression of iNOS was confirmed indirectly by nitrite measurement. When selective iNOS inhibitors were treated, the protective effect of $TNF{\alpha}$ on cell death was partially blocked, suggesting that iNOS expression was involved in controlling cell death. Exogenously added NO substrate (L-arginine) and NO donors (sodium nitroprusside and S-nitroso-N-acetylpenicillamine) also inhibited the cell death induced by serum deprivation. These results suggest that NO has protective effect on bovine cerebral endothelial cell death induced by serum-deprivation and that iNOS is one of the possible target molecules by which $NF-_{\kappa}B$ exerts its cytoprotective effect.

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Demethoxycurcumin from Curcuma longa Rhizome Suppresses iNOS Induction in an in vitro Inflamed Human Intestinal Mucosa Model

  • Somchit, Mayura;Changtam, Chatchawan;Kimseng, Rungruedi;Utaipan, Tanyarath;Lertcanawanichakul, Monthon;Suksamrarn, Apichart;Chunglok, Warangkana
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1807-1810
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    • 2014
  • Background: It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 ${\mu}M$ for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.

Effect of Coptidis Rhizoma Steamed with Rice Wine on Gastroduodenal Mucosa of Mouse through Inhibiting iNOS Activation (주증황련(酒蒸黃連)이 iNOS 활성 억제를 통해 생쥐 위.십이지장 점막에 미치는 영향)

  • Kim, Myung-Ho;Lim, Seong-Woo
    • The Journal of Internal Korean Medicine
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    • v.35 no.3
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    • pp.262-273
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    • 2014
  • Objectives: This study was carried out to investigate the protective effect of Coptidis Rhizoma steamed with rice wine (CR) against gastroduodenal mucosal injury through inhibiting inducible nitric oxide synthase (iNOS) activation. Methods: In in vitro experiment, LPS-induced RAW 264.7 macrophages were treated with CR(0.4, 0.6, 0.8, 1.0 mg/ml) and iNOS mRNA expression and nitric oxide (NO) production were measured. In in vivo experiment normal group mice were treated with neither ethanol nor CR. Both control and sample group mice were orally administrated with ethanol. Five hours after ethanol administration control group mice were orally administrated with distilled water, sample group mice were orally administrated with CR. After three days administration, gastroduodenal mucosa of mice was observed histopathologically and iNOS, nuclear factor-kappa B (NF-${\kappa}B$) activation were observed immunohistochemically. Results: In in vitro experiment iNOS mRNA expression and NO production in LPS-induced RAW 264.7 macrophages were decreased by CR dose-dependently. In in vivo experiment, gastroduodenal mucosal injury was repaired by CR and iNOS, NF-${\kappa}B$ activation in gastroduodenal mucosa were decreased by CR. Conclusions: Coptidis Rhizoma steamed with rice wine has a protective effect against gastroduodenal mucosal injury through inhibiting iNOS activation.

Pseudoguaianolides Isolated from Iunla britannica vats. chinenis as Inhibitory Constituents against Inducible Nitric Oxide Synthase

  • Lee, Hyun-Tai;Yang, Seung-Won;Kim, Kyeong-Ho;Seo, Eun-Kyeong;Mar, Woongchon
    • Archives of Pharmacal Research
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    • v.25 no.2
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    • pp.151-153
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    • 2002
  • Three pseudoguaianolide type sesquiterpenes, bigelovin(1), 2,3-dihydroaromaticin (2), and ergolide (3) were isolated as inhibitory constituents against inducible nitric oxide synthase (iNOS) from the flowers of Inula britannica var. chinensis. Bigelovin (1) exhibited a highly potent inhibitory activity on lipopolysaccharide (LPS)-induced iNOS in murine macrophage RAW 264.7 cells with an $IC_{50}$ value of 0.46 mM, which is about 8 times more potent than the known selective inhibitor of iNOS, $L-N^6-(1-iminoethyl)Iysine{\;}(IC_{50}{\;}3.49{\;}{\mu}M)$. 2,3-Dihydroaromaticin (2) and ergolide (3) also exhibited potent inhibitory activities on LPS-induced iNOS with $IC_{50}$ values of 1.05 and $0.69{\;}{\mu}M$, respectively.

Tandem Repeats (CCTTT)n in the Promoter of iNOS Gene in Korean Genome

  • Baek, Sun-Ah;Yoo, Min
    • Biomedical Science Letters
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    • v.15 no.2
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    • pp.167-170
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    • 2009
  • Nitric oxide is an important factor to regulate the biochemical reactions in the body such as expansion of blood vessel, neural conduction and antimicrobial activity. There are two forms of nitric oxide synthase and iNOS has attracted most attention because it is involved in the development of diabetes and cardiac disease condition. There are several regulatory sequences in the promoter region of iNOS gene. One of them is (CCTTT)n. It has been reported that the number of tandem repeat of (CCTTT)n varies from population to population. So, we analyzed (CCTTT)n polymorphism in Korean genome for the purpose of comparison. According to our present study Koreans are different from other Asians reported previously because $(CCTTT)_{10}$ is the highest incidence as opposed to $(CCTTT)_{12}$ for other countries. This study should facilitate the understanding of the expression of iNOS gene in different population.

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Inhibition of NF-kB/Rel by Paclitaxel in Mouse Macrophages

  • Lim, Jin-Soo;Lee, Seog-Ki;Jeon, Young-Jin
    • Toxicological Research
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    • v.23 no.1
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    • pp.19-24
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    • 2007
  • We demonstrate that paclitaxel, an antitumor agent derived from yew tree, inhibits LPS- and $IFN-{\gamma}$-induced NF-kB/Rel activation in RAW 264.7 cells. Previously, paclitaxel ($>10{\mu}M$) has been known to induce iNOS gene expression in macrophages. However, in the previous report we described that the pretreatment of macrophages with low concentration of paclitaxel ($0.1{\mu}M$) for 8 h inhibited LPS-induced iNOS gene expression. Pretreatment of RAW 264.7 cells with paclitaxel significantly inhibited NF-kB/Rel transcriptional activation. Electrophoretic mobility shift assay further confirmed that pretreatment of macrophages with paclitaxel inhibited NF-kB/Rel DNA binding. Taxotere, a semisynthetic analog of paclitaxel, also inhibited LPS- and $IFN-{\gamma}$-induced iNOS gene expression. Collectively, these series of experiments indicate that paclitaxel inhibits iNOS gene expression by blocking NF-kB/Rel activation.