• Title, Summary, Keyword: iNOS

Search Result 1,525, Processing Time 0.05 seconds

Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus

  • Byun, Jong-Seon;Lee, Sang-Hyun;Jeon, Seong-Ho;Kwon, Yong-Soo;Lee, Hee-Jae;Kim, Sung-Soo;Kim, Young-Myeong;Kim, Myong-Jo;Chun, Wan-Joo
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.13 no.4
    • /
    • pp.265-271
    • /
    • 2009
  • Nitric oxide (NO) has both neuroprotective and neurotoxic effects depending on its concentration and the experimental model. We tested the effects of NG-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and aminoguanidine, a selective inducible NOS (iNOS) inhibitor, on kainic acid (KA)-induced seizures and hippocampal CA3 neuronal death. L-NAME (50 mg/kg, i.p.) and/or aminoguanidine (200 mg/kg, i.p.) were administered 1 h prior to the intracerebroventricular (i.c.v.) injection of KA. Pretreatment with L-NAME significantly increased KA-induced CA3 neuronal death, iNOS expression, and activation of microglia. However, pretreatment with aminoguanidine significantly suppressed both the KA-induced and L-NAME-aggravated hippocampal CA3 neuronal death with concomitant decreases in iNOS expression and microglial activation. The protective effect of aminoguanidine was maintained for up to 2 weeks. Furthermore, iNOS knockout mice ($iNOS^{-1-}$) were resistant to KA-induced neuronal death. The present study demonstrates that aminoguanidine attenuates KA-induced neuronal death, whereas L-NAME aggravates neuronal death, in the CA3 region of the hippocampus, suggesting that NOS isoforms play different roles in KA-induced excitotoxicity.

Effects of Seman Armenicae and Radix Trichosanthis on the iNOS expression and superoxide formation in the RAW264.7 cells (행인 과루인 추출물이 마우스 대식세포주인 RAW264.7 세포주의 iNOS 발현 및 Superoxide 형성에 미치는 영향)

  • Park, Joug-Un;Moon, Seok-Jae;Moon, Goo;Won, Jin-Hee
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
    • /
    • v.5 no.1
    • /
    • pp.137-150
    • /
    • 1999
  • Macrophage play a major role in host defence against infection and tumor development and this activity is regulated through the production of several mediators. In particular, the production of NO by macrophages mediates killing or growth inhibition of tumor cells, bacteria, fungi and parasites. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammator and auto-immune disease. Therefore, it would be valuable to develop potent and selective inhibitors of for potential therapeutic use. Thus the agent that supprees the expression of iNOS mRNA or enzyme protein will be usefull for the prevention of various diseases. We are intersted in identifying selective inhibitiors of iNOS which might be useful intreating inflammatory human diseases. In summary, we have demenstrated that scopoletin, isolated from Seman Armenicae and Radix Trichosanthis the production of NO induced by $IFN-\gammer$ plus LPS in RAW 264.7 macrophages, The mechanism for the inhibition of NO production was due to suppression of the expression of iNOS mRNA or enzyme protein.

  • PDF

Cheonggi-san Inhibits Atopy Dermatitis in NC/Nga Mouse through Regulation of iNOS mRNA Expresssion & NO production (청기산(淸肌散)의 iNOS 발현과 NO 생성 억제가 NC/Nga 생쥐의 아토피 피부염에 미치는 영향)

  • Ahn, Sang-Hyun;Kim, Ho-Hyun;Kim, Jin-Taek
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.21 no.5
    • /
    • pp.1092-1098
    • /
    • 2007
  • Inducible nitric oxide synthase (iNOS) are important inflammation enzyme and severe up-nitric oxide (NO) production by this enzyme has been intricate with pathogenesis of atopy dermatitis. The present study was designed in order to determine whether Cheonggi-san could inhibit atopy dermatitis through modulation of iNOS mRNA expression and NO production. We found that iNOS mRNA expression and NO production in RAW 264.7 macrophages stimulated with lipopolysaccharide dose-dependantly decreased by Cheonggi-san extract treatment (0.5 - 2.0 mg/ml). The distribution of iNOS positive reacted cell in NC/Nga mice with atopy dermatitis were decreased by Cheonggi-san extract treatment (2.5 ml/kg/day) and apoptosis were increased. These data likely indicate that Cheonggi-san may act as inflammatory regulator for atopy dermatitis and may be possible to develop useful agent for chemoprevention of NO intricate inflammatory diseases.

Androgen Hormone Inhibits Expression of iNOS and COX-2 Protein in Rat Vascular Smooth Muscle Cell

  • Bae, Hwa-Young;Park, Ji-Eun;Jeon, Eun-Mi;Kang, Young-Jin;Lee, Kwang-Youn;Choi, Hyoung-Chul
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.9 no.4
    • /
    • pp.215-221
    • /
    • 2005
  • We investigated the effects of testosterone and dihydrotestosterone on inflammatory response of iNOS and COX-2 expression in rat vascular smooth muscle cells. Rat vascular smooth muscle cells (VSMC) stimulated with bacterial lipopolysaccharide $(LPS;\;10{\mu}g/ml)$ for 24 hours were incubated with increasing amounts of testosterone and dihydrotestosterone (1 and 100 nM). LPS was found to induce inflammatory response of iNOS and COX-2 mRNA and protein in VSMC. These processes were affected by male sex steroid hormones. For 3 hours, however, pretreatment of the cells with 100 nM each of testosterone and dihydrotestosterone suppressed LPS induced iNOS and COX-2 protein expression. RT-PCR analysis revealed that testosterone and dihydrotestosterone did not inhibit mRNA expression of iNOS and COX-2 stimulated by 24 hours of LPS incubation. Proliferation rate was slower in VSMC treated with testosterone and dihydrotestosterone. Testosterone enhanced androgen receptor expression, and LPS significantly reduced androgen receptor protein expression in VSMC. These results indicate that the expression of both iNOS and COX-2 proteins was suppressed by testosterone and dihydrotestosterone in LPS stimulated VSMC and leading to reduction of vascular inflammation.

Sopungdojeok-San Inhibits Atopy-liked Dermal Inflammation through Regulation of iNOS mRNA Expresssion & NO production (소풍도적산의 iNOS 발현과 NO 생성 억제가 아토피 피부염에 미치는 영향)

  • Ahn, Sang-Hyun;Kim, Jin-Taek
    • Herbal Formula Science
    • /
    • v.15 no.1
    • /
    • pp.199-211
    • /
    • 2007
  • Inducible nitric oxide synthase (iNOS) are important inflammation enzyme and severe up-nitric oxide (NO) production by this enzyme has been intricated with pathogenesis of inflammation diseases as atopy dermatitis. The present study was designed in order to determine whether Sopungdojeok-san could inhibit atopy dermatitis through modulation of iNOS mRNA expression and NO production, We found that iNOS mRNA expression and NO production in RAW 264.7 macrophages stimulated with lipopolysaccharide dose-dependantly decreased by Sopungdojeok-san extract treatment (0.4 - 1.0 mg/ml). The distribution of iNOS positive reacted cell in atopy dermatitis elicited skin of mice were remarkably decreased by Sopungdojeok-san administration (2.5 ml/kg/day). The SOD ability of Sopungdojeok-san were dose-dependantly increased from 0.6 mg/ ml than butylated hydroxyanisole. These data likely indicate that Sopungdojeok-san may act as inflammatory regulator for atopy dermatitis may be possible to develop useful agent for chemopreventation of NO-intricate inflammatory diseases.

  • PDF

Cimicifuga heracleifolia Extract Induces iNOS Expression via a Nuclear Factor-${\kappa}B$-dependent Pathway in Mouse Peritoneal Macrophages

  • Lee, Kyoung-In;Tabassum, Nadia;Pyo, Byoung-Sik;Kim, Sun-Min;Lee, Ik-Soo;Jung, Da-Woon;Yim, Soon-Ho
    • Natural Product Sciences
    • /
    • v.20 no.4
    • /
    • pp.227-231
    • /
    • 2014
  • Cimicifuga heracleifolia extract (CHE) was investigated for its effects on the release of nitric oxide (NO) and at the level of inducible nitric oxide synthase (iNOS) gene expression in mouse macrophages. We found that C. heracleifolia elicited a dose-dependent increase in NO production and the level of iNOS mRNA. Since, iNOS transcription has been shown to be under the control of the transcription factor $NF-{\kappa}B$, the effects of CHE on $NF-{\kappa}B$ activation were examined. Transient expression assays with $NF-{\kappa}B$ binding sites linked to the luciferase gene revealed that the increased level of iNOS mRNA, induced by CHE, was mediated by the $NF-{\kappa}B$ transcription factor complex. By using DNA fragments containing the $NF-{\kappa}B$ binding sequence, CHE was shown to activate the protein/DNA binding of $NF-{\kappa}B$ to its cognate site, as measured by electrophoretic mobility shift assay. These results demonstrate that C. heracleifolia stimulates NO production and is able to up-regulate iNOS expression through $NF-{\kappa}B$ transactivation.

Expression of TRPV1 and iNOS in the Dorsal Root Ganglion Exposed by Autologous Nucleus Pulposus in the Rat

  • Kim, Su-Jeong;Seo, Jeong-Min;Cho, Yun-Woo;Park, Hea-Woon;Lee, Joon-Ha;Hwang, Se-Jin;Ahn, Sang-Ho
    • The Journal of Korean Physical Therapy
    • /
    • v.22 no.3
    • /
    • pp.71-77
    • /
    • 2010
  • Purpose: To determine whether upregulation of inducible nitric oxide synthase (iNOS) transcription and translation is related to radicular pain in a model of lumbar disc herniation. Also, to investigate the temporal changes of mRNA expression of iNOS and the identity of iNOS and transient receptor potential vanilloid (TRPV) 1 channel expression cells in dorsal root ganglion (DRG) of a model of lumbar disc herniation. Methods: A lumbar disc herniated rat model was developed by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the DRG. Rats were tested for mechanical allodynia of the plantar surface of both hind paws 2 days before surgery and 1, 5, 10, 20 and 30 days postoperatively. Reverse transcription polymerase chain reaction (RT-PCR) was used to follow iNOS mRNA expression. To stain iNOS and TRPV1 in DRG, an immunohistochemical study was done 10 days after surgery. Results: A significant drop in mechanical withdrawal threshold on the ipsilateral and contralateral hind paws was observed 1 day after surgery and was prolonged to 30 days in rats with lumbar disc herniation. The expression of mRNA for iNOS peaked at postoperative day 10 on both sides of the DRG. iNOS-positive sensory neurons in the DRG varied in size from large to small diameter cells. A majority of small and intermediate sensory neurons were TRPV1-positive cells. Double immunofluorescence staining for TRPV1 and iNOS revealed that most intermediate TRPV1-positive sensory neurons co-localized with iNOS-positive neurons. Conclusion: Nucleus pulposus-induced mechanical allodynia can be generated without mechanical compression. This pain is related to temporal changes in expression of iNOS mRNA in the DRG. Co-localization of TRPV1 and iNOS in intermediate neurons of the DRG is correlated with pain modality and intensity.

Inhibition by Higenamine of Lipopolysaccharide-induced iNOS mRNA Expression and NO Production in Rat Aorta (Lipopolysaccharide로 활성화시킨 흰쥐 혈관의 iNOS 발현에 대한 Higenamine의 효과)

  • Kang Young-Jin;Lee Goun-Woo;Ku Eui-Bon;Lee Hoi-Young;Chang Ki-Churl
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.1 no.3
    • /
    • pp.297-302
    • /
    • 1997
  • Higenamine was widely used as traditional remedy for the treatment of rhumatoid arthritis. Nitric oxide(NO) may be a critical mediator in this inflammatory disease. Synovial tissue from humans with inflammatory arthritis expresses NOS2(iNOS) mRNA and protein, and generates NO in vitro. We therefore, investigated the effect of higenamine on the induction of nitric oxide synthase(NOS) promoted by lipopolysaccharide(LPS). Prophylactic application of higenamine selectively prevented LPS-primed initiation of L-arginine-induced relaxation and restored rhenylephrine(PE)-induced contraction in rat aorta. LPS-stimulated nitrite production in the incubation medium was reduced by higenamine. Furthermore, RT-PCR and Northern analysis indicated that higenamine reduced iNOS expression primed by LPS in rat aorta. These results suggest that higenamine prevents LPS-promoted induction of NOS in vascular smooth muscle.

  • PDF

Effects of Fucoidan on Neuronal Cell Proliferation: Association with NO Production through the iNOS Pathway

  • Lee, Hye-Rim;Do, Hang;Lee, Sung-Ryul;Sohn, Eun-Soo;Pyo, Suhk-Neung;Son, Eun-Wha
    • Preventive Nutrition and Food Science
    • /
    • v.12 no.2
    • /
    • pp.74-78
    • /
    • 2007
  • Fucoidan, that is high-molecular-weight sulfated polysaccharides extracted from brown seaweeds has been shown to elicit various biological activities. Here, we investigated the effects of fucoidan on cell proliferation and nitric oxide (NO) production in neuronal blastoma cell (SH-SY5Y). In the present study, we demonstrated that fucoidan treatment resulted in increase of cell proliferation and NO production. When cells were treated with amyloid-${\beta}$ (A${\beta}$) in the absence or presence of fucoidan, fucoidan recovered the cell viability decreased by A${\beta}$ peptides. To further determine whether nitric oxide synthase (NOS) is involved in proliferative effect of fucoidan, cells were treated with NOS inhibitors in the absence or presence of fucoidan. Selective constitutive nitric oxide synthase (cNOS) inhibitor, diphenylene iodonium chloride (DPI), caused a decrease of cell viability, whereas cell viability was increased by specific inducible nitric oxide synthase (iNOS) inhibitor, S-methylisothiourea (SMT), in the fucoidan-untreated cells. Treatment with fucoidan inhibited the cell viability decreased in DPI-exposed cells. In contrast, fucoidan had no effect on cell growth in SMT-treated cells, indicating that cNOS may not play a role in the proliferation of fucoidan-treated cells. The present data suggest that fucoidan has proliferative and neuroprotective effects and these effects may be associated with iNOS.

Inhibition of Lipopolysaccaride-induced Inducible Nitric Oxide (iNOS) mRNA Expression and Nitric Oxide Production by Higenamine in Murine Peritoneal Macrophages

  • Lee, Hoi-Young;Lee, Jang-Soon;Kim, Eun-Ju;Han, Jeung-Whan;Lee, Hyang-Woo;Kang, Young-Jin;Chang, Ki-Churl
    • Archives of Pharmacal Research
    • /
    • v.22 no.1
    • /
    • pp.55-59
    • /
    • 1999
  • Nitric oxide synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation in rheumatic and autoimmune diseases. The effects of higenamine, a tetrahydroisoquinoline compound, on induction of NOS by bacterial lipopolysaccaride (LPS) were examined in murine peritoneal macrophages. LPS-induced nitrite/nitrate production was markedly inhibited by higenamine which at 0.01 mM, decreased nitrite/nitrate levels by $48.7{\pm}4.4%$This was comparable to the inhibition of LPS-induced nitrite/nitrate production by tetrandrin ($49.51{\pm}2.02%$). at the same concentration. Northern and Western blot analysis of iNOS expression demonstrated that iNOS expression was significantly attenuated following co-incubation of peritoneal macrophages with LPS (10 $\mu\textrm{g}$/m;; 18hrs) and higenamine (0.001, 0.,01 mM; 18hrs). These results suggest that higenamine can inhibit LPS-induced expression of iNOS mRNA in murine peritoneal macrophages. The clinical implications of these findings remain to be established.

  • PDF