• Title, Summary, Keyword: Nitric oxide synthase 3

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Inhibitory Effect of Esculetin on the Inducuble Nitric Oxide Synthase Expression in TNF-stimulated 3T3-L1 Adipocytes

  • Yang, Jeong-Yeh
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.5
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    • pp.283-287
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    • 2003
  • While nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) is beneficial for host survival, it is also detrimental to the host. Thus, regulation of iNOS gene expression may be an effective therapeutic strategy for the prevention of unwanted reactions at various pathologic conditions. During the screening process for the possible iNOS regulators, we observed that esculetin is a potent inhibitor of cytokine-induced iNOS expression. The treatment of 3T3-L1 adipocytes with the tumor necrosis factor-${\alpha}$ (TNF) induced iNOS expression, leading to enhanced NO production. TNF-induced NO production was inhibited by esculetin in a dose-dependent manner. Esculetin inhibited the TNF-induced NO production at the transcriptional level through suppression of iNOS mRNA and subsequent iNOS protein expression. These results suggest esculetin, a component of natural products, as a naturally occurring, nontoxic means to attenuate iNOS expression and NO-mediated cytotoxicity.

Elevation of Nitric Oxide Synthase Activity by Dimethyladenosine from Silkworm Pupae in Aged Rats

  • Ahn, Mi-Young;Han, Jea-Woong;Hong, Yoo-Na;Hwang, Jae-Sam
    • Toxicological Research
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    • v.24 no.3
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    • pp.169-174
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    • 2008
  • This study examined the mechanisms underlying the effects of the vasorelaxation active substance(VAS), dimethyladenosine-5'-L-arabinose, and its partial purification fraction on nitric oxide synthase in improving erectile dysfunction with particular focus on the nitric oxide (NO)-cGMP pathways. Two rat models, 9-month-old SD rats and 11-month-old SD rats, were given VAS(40 mg/kg per day) for 4 days, The aqueous fraction of silworm male pupae extract; semi-purified VAS(100 mg/kg per day) for 10 days, respectively. The NOS activities of the following three enzymes were examined: neuronal NO synthase(nNOS), inducible NOS(iNOS), endothelial NOS(eNOS), vascular endothelial growth factor on endothelial cells(VEGF) and anti-inflammation effect of Tumor necrosis factor-$\alpha$. The results showed increases in the nitric oxide synthase activities. Western blotting of the tissue homogenate showed an increase in the nNOS level in the brain and tongue, and an increase in the endothelial NO synthase(eNOS) level in penis. However, there was little association with VEGF production in HUVEC endothelial cells and no relationship with TNF-$\alpha$ which showed low levels.

Inducible nitric oxide synthase is involved in neuronal death induced by trimethyltin in the rat hippocampus (Trimethyltin에 의한 랫드 해마의 신경세포 사멸과 iNOS의 연관성)

  • Jang, Sukwon;Choi, Sungyoung;Park, Changnam;Ahn, Meejung;Shin, Taekyun;Kim, Seungjoon
    • Korean Journal of Veterinary Research
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    • v.51 no.3
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    • pp.185-191
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    • 2011
  • Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.

Nitric Oxide and Hydrogen Peroxide Production are Involved in Systemic Drought Tolerance Induced by 2R,3R-Butanediol in Arabidopsis thaliana

  • Cho, Song-Mi;Kim, Yong Hwan;Anderson, Anne J.;Kim, Young Cheol
    • The Plant Pathology Journal
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    • v.29 no.4
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    • pp.427-434
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    • 2013
  • 2R,3R-Butanediol, a volatile compound produced by certain rhizobacteria, is involved in induced drought tolerance in Arabidopsis thaliana through mechanisms involving stomatal closure. In this study, we examined the involvement of nitric oxide and hydrogen peroxide in induced drought tolerance, because these are signaling agents in drought stress responses mediated by abscisic acid (ABA). Fluorescence-based assays showed that systemic nitric oxide and hydrogen peroxide production was induced by 2R,3R-butanediol and correlated with expression of genes encoding nitrate reductase and nitric oxide synthase. Co-treatment of 2R,3R-butanediol with an inhibitor of nitrate reductase or an inhibitor of nitric oxide synthase lowered nitric oxide production and lessened induced drought tolerance. Increases in hydrogen peroxide were negated by co-treatment of 2R,3R-butanediol with inhibitors of NADPH oxidase, or peroxidase. These findings support the volatile 2R,3R-butanediol synthesized by certain rhizobacteria is an active player in induction of drought tolerance through mechanisms involving nitric oxide and hydrogen peroxide production.

Changes of Specific Activity and Regulation of Nitric Oxide Synthase during Liver Regeneration after Partial Hepatectomy

  • Lee, Young-Jin;Nam, Suk-Woo;Seo, Dong-Wan;An, Sung-Whun;Ko, Young-Kwun;Sung, Dae-Seok;Han, Jung-Whan;Lee, Hyang-Woo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • pp.185-185
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    • 1996
  • Nitric oxide synthase(NO Synthase:E.C.1.14.13.39)는 생체내에서 L-arginine을 기질로 하여 citrulline과 nitric oxide(NO)를 생성하는 효소로서, 최근 연구에 의하면 2/3 부분 간 절제술 후 prereplicative phase동안에 발현되는 것으로 알려져 있다. 한편, 생체내에서 NO Synthase에 상경적 길항제인 methylarginine에 관해서도 수년간 많은 연구가 진행되어 왔다. 이들의 생성 기전은 protein methylation에 의해 생성된 methylated protein이 생체 내에서 분해되어 생성된다고 알려져 있으나, 정확한 기전에 대해서는 아직 논란의 여지가 많다. 따라서, 본 연구에서는 In vivo 실험을 통해 부분 간 절제술 후 시간대별로 간 조직에서의 NO Synthase 활성도와 혈청에서 NO의 최종 대사물인 Nitrite/Nitrate를 측정하였으며, 또한 NO Synthase 조절에 관여하는 세포내 기질인 arginine과 억제 인자인 methylarginine함량을 간 조직 및 혈청에서 측정하고, 세포 신호 전달체계에 관여하는 cyclic GMP 함량을 측정함으로써, 부분 간 절제술 후 간 재생동안에 NO Synthase 활성도와 methylarginine 및 arginine과의 상관 관계를 규명하고, 간 재생동안, 생성된 nitric oxide의 역할을 연구하려한다.

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Role of Angiotensin II and Nitric Oxide in the Rat Paraventricular Nucleus

  • Yang, Eun-Kyoung
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.1
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    • pp.41-46
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    • 2001
  • To investigate the mutual relationship between angiotensin II (Ang II) and nitric oxide (NO) in paraventricular nucleus (PVN), Ang II receptor type Ia $(AT_{1A}),$ type Ib $(AT_{1B}),$ endothelial constitutive nitric oxide synthase (ecNOS), and neuronal constitutive nitric oxide synthase (ncNOS) mRNA levels of rat PVN were measured after unilateral carotid artery ligation. $AT_{1A}$ and $AT_{1B}$ mRNA levels were markedly elevated 6 hrs after unilateral carotid artery ligation. Losartan injection $(10\;{\mu}g/0.3\;{\mu}l)$ into the PVN augmented of the increment of $AT_{1A}$ and $AT_{1B}$ mRNAs It also increased ecNOS gene expression. In addition, $AT_{1B}$ mRNA levels increased after N-nitro-L-arginine methyl ester (L-NAME) injection $(50\;{\mu}g/0.3\;{\mu}l)$ into the PVN. These results suggest that Ang II and NO in the rat PVN may interplay, at least in part, through regulation of gene expression of ecNOS and $AT_{1B},$ respectively.

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EFFECTS OF NITRIC OXIDE SYNTHASE INHIBITORS ON OSTEOCLAST-LIKE CELL FORMATION

  • Ahn, Seung-Kyu;Kim, Jung-Kun;Cha, Kyung-Suk
    • The korean journal of orthodontics
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    • v.25 no.6
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    • pp.715-722
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    • 1995
  • Orthodontic tooth movement in response to orthodontic force results from actions of osteoclasts and osteeoblasts in the cell level. Convincing evidence has now been provided to support the view that osteoclasts are derived from mononuclear cells that originate in the bone marrow or other hematopoietic organs and they migrate to the bones via vascular routes. Nitric oxide(NO), which accounts for the biological properties of endothelium-derived relaxing factor(EDRF), is the endogenous stimulator of soluble guanylate cylase. The discovery of the formation of nitric oxide(NO) from L-arginine in mammalian tissues and its biological roles has, in the last 7 years, thrown new light onto many areas of research. Data from experiments in vitro showed that N-metyl-L-arginine(L-NMA) and L-nitro-L- arginine(L-NAME) are competitive inhibitors of nitric oxide synthase. This study suggest that the multinucleated cells in our culture have characteristics of osteoclasts and that the potential bone cell activity of nitric oxide in vitro may be mediated in part by stimulation of marrow mononuclear cells to form osteoclast-like cells. Bone marrow cells were obtaineed from tibia of 19-days old chick embryo. After sacrifice, tibia was quickly dissected and the bone were then split to expose the medullary bone. The cells were attached for 4 hours and the nonadherent cells were collected. Marrow cells weere cultured in 96-well plate in medium 199. To examine the number of TRAP-positive multinucleated cells(MNCs), $10^{-8}\;M\;Vit=D_3$ and various concentration of L-NMA and L-NAME weere added at the beginning of cultures and with each medium change. After 7 days of culture. tartrate-resistant acid phosphatase(TRAP) staining was performed for microscopic evaluation. Cells haying more than three nuclei per cell were counted as MNCs. The obsrved results were as follows;1. 1,25-dihydroxyvitamine $D_3$ stimulated the osteoclast-like multinucleated cells in cultures of chick embryo bone marrow. 2. Nitric oxide synthase inhibitors(NOSI ; N-NMA, N-NAME) stimulated the osteoclast-like cells in cultures of chick embry bone marrow. 3. 1,25-dihydroxyvitamine$D_3$ and nitric oxide synthase inhibitors did not appear to have additive effect on the generation of TRAP-positive MNCs. These results suggest that nitric oxide synthase inhibitors may stimulate the osteoclast-like multinucleated cell formation and fusion in cultures of chick bone marrow.

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Inhibitors of Inducible Nitric Oxide Synthase Expression from Artemisia iwayomogi

  • Ahn, Hanna;Kim, Ji-Yeon;Lee, Hwa-Jin;Kim, Yong-Kyun;Ryu, Jae-Ha
    • Archives of Pharmacal Research
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    • v.26 no.4
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    • pp.301-305
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    • 2003
  • Nitric oxide (NO) is an important bioactive agent that mediates a wide variety of physiological and pathophysiological events. NO overproduction by inducible nitric oxide synthase (iNOS) results in severe hypotension and inflammation. This investigation is part of a study to discover new iNOS inhibitors from medicinal plants using a macrophage cell culture system. Two sesquiterpenes (1 and 2) were isolated from Artemisia iwayomogi (Compositae) and were found to inhibit NO synthesis ($IC_{50} 3.64 \mu g/mL and 2.81 \mu$g/mL, respectively) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Their structures were identified as 3-Ο-methyl-iso-secotanapartholide (1) and iso-secotanapartholide (2). Compounds 1 and 2 inhibited the LPS-induced expression of the iNOS enzyme in the RAW 264.7 cells. The inhibition of NO production via the down regulation of iNOS expression may substantially modulate the inflammatory responses.

Identification and Characterization of Nitric Oxide Synthase in Salmonella typhimurium

  • Choi, Don-Woong;Oh, Hye-Young;Hong, Sung-Youl;Han, Jeung-Whan;Lee, Hyang-Woo
    • Archives of Pharmacal Research
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    • v.23 no.4
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    • pp.407-412
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    • 2000
  • The presence of the nitric oxide synthase (NOS) enzyme from Salmonella typhimurium (S. typhimurium) was identified by measuring radiolabeled L-$[^3H]$citrulline and NO, and Western blot analysis. NOS was partially purified by both Mono Q ion exchange and Superose 12HR size exclusion column chromatography, sequentially. The molecular weight of NOS was estimated to be 93.3 kDa by Western blot analysis. The enzyme showed a significant dependency on the typical NOS cofactors; an apparent Km for L-arginine of 34.7 mM and maximum activity between $37^{\circ}C$ and $43^{\circ}C$. The activity was inhibited by NOS inhibitors such as aminoguanidine and $N^{G}$ $N^{G}$-dimethyl-L-arginine. taken together, partially purified NOS in S. typhimurium is assumed to be a different isoform of mammalian NOSs.OSs.

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Effect of Thesium Chinense Turczaninow on Breast Cancer Chemopreventive enzyme activity in In vitro (In vitro에서의 댑싸리하고초의 유방암예방효소 활성에 미치는 영향)

  • Shon, Yun-Hee;Kim, Mee-Kyung;Park, Sun-Dong;Nam, Kyung-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.3
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    • pp.675-679
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    • 2006
  • The effect of water extract from Thesium chinese Turczaninow (TCTW) on proliferation of human breast cancer cells, nitric oxide production, nitric oxide synthase expression, and ornithine decarboxylase activity was tested. TCTW inhibited the growth of both estrogen-independent MDA-MB-231 and estrogen-dependent MCF-7 human breast cancer cells. Lipopolysaccharide-induced nitric oxide (NO) production was significantly reduced by TCTW at the concentrations of 1.0 (p<0.05) and 5.0 mg/ml (p<0.005). Expression of inducible nitric oxide synthase (iNOS) was also suppressed with the treatment of TCTW in Western blot analysis. TCTW inhibited induction of ornithine decarboxylase by 12-O-tetradecanoylphorbol-13-acetate (TPA), a key enzyme of polyamine biosynthesis, which is enhanced in tumor promotion. Therefore, TCTW is worth further investigation with respect to breast cancer chernoprevention or therapy.