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1.
Dehydroepiandrosterone inhibits lipopolysaccharide-induced nitric oxide production in BV-2 microglia 总被引:2,自引:0,他引:2
Levels of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) decline during aging and reach even lower levels in Alzheimer's disease (AD). DHEA is known to exhibit a variety of functional activities in the CNS, including an increase of memory and learning, neurotrophic and neuroprotective effects, and the reduction of risk of age-related neurodegenerative disorders. However, the influence of DHEA on the immune functions of glial cells is poorly understood. In this study, we investigated the effect of DHEA on activated glia. The production of inducible nitric oxide synthase (iNOS) was studied in lipopolysaccharide (LPS)-stimulated BV-2 microglia, as a model of glial activation. The results showed that DHEA but not DHEAS significantly inhibited the production of nitrite in the LPS-stimulated BV-2 cell cultures. Pretreatment of BV-2 cells with DHEA reduced the LPS-induced iNOS mRNA and protein levels in a dose-dependent manner. The LPS-induced iNOS activity in BV-2 cells was decreased by the exposure of 100 microM DHEA. Moreover, DHEA suppressed iNOS gene expression in LPS-stimulated BV-2 cells did not require de novo synthesis of new proteins or destabilize of iNOS mRNA. Since DHEA is biosynthesized by astrocytes and neurons, our findings suggest that it might have an important regulatory function on microglia. 相似文献
2.
Abu Shadat M. Noman Naoki Koide Imtiaz I.-E. Khuda Jargalsaikhan Dagvadorj Gantsetseg Tumurkhuu Yoshikazu Naiki Takayuki Komatsu Tomoaki Yoshida & Takashi Yokochi 《FEMS immunology and medical microbiology》2009,56(3):204-211
The effect of thalidomide on lipopolysaccharide-induced nitric oxide (NO) production was studied using RAW 264.7 macrophage-like cells. Thalidomide significantly inhibited lipopolysaccharide-induced NO production via reduced expression of an inducible NO synthase. Thalidomide reduced the phosphorylation of the p65 nuclear factor-κB subunit, inhibitory κB (IκB) and IκB kinase in lipopolysaccharide-stimulated cells. However, thalidomide did not affect the expression of interferon-β (IFN-β) and interferon regulatory factor-1 in response to lipopolysaccharide. Further, thalidomide inhibited the MyD88 augmentation in lipopolysaccharide-stimulated cells, whereas it did not alter the expression of TIR domain-containing adaptor-inducing IFN-β in the MyD88-independent pathway. Thalidomide significantly inhibited the NO production in response to Pam3 Cys, CpG DNA and imiquimod as MyD88-dependent Toll-like receptor (TLR) ligands, but not polyI:C as a MyD88-independent TLR ligand. Therefore, thalidomide was suggested to inhibit lipopolysaccharide-induced NO production via downregulation of the MyD88-dependent signal pathway. The anti-inflammatory action of thalidomide might be involved in the prevention of lipopolysaccharide-mediated lethality in mice. 相似文献
3.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):490-494
The methanolic extract of Dictamnus dasycarpus root barks afforded one new glycosidic quinoline alkaloid, 3-[1β-hydroxy-2-(β-D-glucopyranosyloxy)-ethyl)-4-methoxy-2(1H)-quinolinone (1), together with nine known compounds, preskimmianine (2), 8-methoxy-N-methylflindersine (3), dictamine (4), γ-fagarine (5), halopine (6), skimmianine (7), dictangustine-A (8), iso-γ-fagarine (9), isomaculosidine (10). The isolated alkaloids significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV2 cells. Among them, compounds 3 and 7 showed the most potent inhibitory activities on LPS-induced NO production. 相似文献
4.
Delta-9-tetrahydrocannabinol protects cardiac cells from hypoxia via CB2 receptor activation and nitric oxide production 总被引:2,自引:0,他引:2
Shmist YA Goncharov I Eichler M Shneyvays V Isaac A Vogel Z Shainberg A 《Molecular and cellular biochemistry》2006,283(1-2):75-83
Delta-9-tetrahydrocannabinol (THC), the major active component of marijuana, has a beneficial effect on the cardiovascular
system during stress conditions, but the defence mechanism is still unclear. The present study was designed to investigate
the central (CB1) and the peripheral (CB2) cannabinoid receptor expression in neonatal cardiomyoctes and possible function
in the cardioprotection of THC from hypoxia. Pre-treatment of cardiomyocytes that were grown in vitro with 0.1 – 10 μM THC for 24 h prevented hypoxia-induced lactate dehydrogenase (LDH) leakage and preserved the morphological
distribution of α-sarcomeric actin. The antagonist for the CB2 (10 μM), but not CB1 receptor antagonist (10 μM) abolished
the protective effect of THC. In agreement with these results using RT-PCR, it was shown that neonatal cardiac cells express
CB2, but not CB1 receptors. Involvement of NO in the signal transduction pathway activated by THC through CB2 was examined.
It was found that THC induces nitric oxide (NO) production by induction of NO synthase (iNOS) via CB2 receptors. L-NAME (NOS
inhibitor, 100 μM) prevented the cardioprotection provided by THC. Taken together, our findings suggest that THC protects
cardiac cells against hypoxia via CB2 receptor activation by induction of NO production. An NO mechanism occurs also in the
classical pre-conditioning process; therefore, THC probably pre-trains the cardiomyocytes to hypoxic conditions. 相似文献
5.
Recent studies have suggested that lipopolysaccharides (LPS) induce nitric oxide (NO) production and defense gene expression in plants. Our current work investigated the signaling mechanism of NO and the role of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 (NPR1) in LPS-induced innate immunity of Arabidopsis (Arabidopsis thaliana). We have provided evidence that LPS-elicited NO generation as well as increased antioxidant enzyme activities capable of maintaining the redox state could be important to protect plants against oxidative damage from pathogen attack. In addition, LPS-activated defense responses, including callose deposition and defense-related gene expression, are regulated through an NPR1-dependent signaling pathway. Our results contribute to elucidation of the signaling mechanism of NO and highlight an important role of NPR1 in modulating LPS-triggered innate immunity in plants. However, further research is necessary to clarify the cross-talk between mitochondria and NO on activating LPS-induced defense responses, and the regulatory mechanism of NO in LPS-induced innate immunity needs further improvement. 相似文献
6.
目的:观察甲醛炎性痛过程中大鼠痛行为、海马一氧化氮合酶(NOS)活性及一氧化氮(NO)含量的变化以及变化的时程及区域特征。方法:采用辐射热甩尾法测定大鼠痛阈变化;采用NADPH—d组织化学法和硝酸还原酶法分别测定大鼠海马NOS表达和No含量。结果:皮下注射甲醛溶液后,大鼠出现伤害性感受反应及痛阈降低。注射甲醛后6h,海马CA1、CA2~3区及DG区NOS阳性细胞数目、阳性细胞染色深度均显著增加。海马NO含量亦显著增加;注射甲醛后12h时这些改变最为显著,48h时恢复至对照组水平。结论:甲醛炎性痛可诱导海马NOS活性增强及NO生成增多.这种改变可发生在海马各区.并具有一定的时程特征。 相似文献
7.
Baudouin E 《Plant biology (Stuttgart, Germany)》2011,13(2):233-242
Nitric oxide (NO) has recently joined the select circle of the ubiquitous molecules of plant signalling networks. Indeed, the last decade has produced a tremendous amount of data that evidence the diversity of physiological situations in which NO is involved in plants and the complexity of NO biology. These data also underline our difficulties in providing simple answers to the cardinal questions of where NO comes from and how the NO message is converted into a physiological response. The identification of NO primary targets and NO-regulated genes provides new opportunities to connect NO biochemistry and NO biology. This review summarises our current understanding of NO signalling, from the generation of the NO message to its execution into a cellular response. The review particularly considers whether and how NO may be responsible for specific signalling in different physiological processes. 相似文献
8.
9.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):887-892
The ethyl acetate (EtOAc) soluble fraction of the 85% ethanol (EtOH) extract of the dried bark of Limonia acidissima potently inhibited nitric oxide (NO) production in lipopolysaccharide (LPS) activated BV-2 cells, a microglial cell line. Bioassay-guided column chromatography separation afforded a new stereoisomer of neolignan, (7’E)-(7R,8S)-4-hydroxy-3,5’-dimethoxy-4’,7-epoxy-8,3’-neolig-7’-en-9,9’-diyil diacetate (1), together with two known lignans, (+)-yangambin (2) and (+)-syringaresinol (3), three known triterpenoids, hederatriol (4), basic acid methyl ester (5), and 3β-hydroxyolean-12-en-11-one (6), and four known fatty acid derivatives, cascarillic acid (7), (+)-α-dimorphecolic acid (8), 8(R)-hydroxylinoleic acid (9), and (6Z,9Z,12Z)-pentadecatrienoic acid (10). The structure of the new compound 1 was elucidated by detailed analysis of spectroscopic data and circular dichroism (CD) spectroscopy. Compounds 1, 3-6, and 8-10 isolated from L. acidissima significantly reduced NO production in LPS-stimulated BV-2 microglia cells. 相似文献
10.
The study was designed to investigate the effect of nimesulide on lipopolysaccharide (LPS)-induced proinflammatory oxidants production by rat alveolar macrophages (AMs). Effects of LPS and nimesulide on antioxidant defense and the expression of inducible nitric oxide synthase (iNOS) were also studied. It was found that nimesulide could scavenge superoxide anions (O2*-), nitric oxide (NO*) and total oxidant burden induced by LPS in AMs in vitro. Approximately 850 nmoles of nimesulide had activity equivalent to one IU of superoxide dismutase (SOD). Further, to confirm the in vitro observation, Male Wistar rats were orally administered with nimesulide (9 mg/kg b. wt. twice daily) for one week followed by intratracheal instillation of 2 microg LPS to stimulate lung inflammation. AMs from bronchoalveolar lavage fluid were collected 18 h after instillation of LPS. Nimesulide pretreatment could inhibit O2*-, NO() and lipid peroxidation in AMs. Nimesulide also suppressed LPS-induced iNOS expression in AMs in vivo and in vitro. Nimesulide could also normalize LPS-induced changes in the levels of superoxide dismutase (SOD), glutathione reductase (GR) and reduced glutathione (GSH) in AMs. Inhibition in production of oxidants in LPS-challenged AMs by nimesulide could be one of the pathways for its anti-inflammatory action. 相似文献
11.
Neuroblastoma cells are capable of hypoxic adaptation, but the mechanisms involved are not fully understood. We hypothesized that caveolin-1 (cav-1), a plasma membrane signal molecule, might play a role in protecting neuroblastoma cells from oxidative injury by modulating nitric oxide (NO) production. We investigated the alterations of cav-1, cav-2, nitric oxide synthases (NOS), and NO levels in human SK-N-MC neuroblastoma cells exposed to hypoxia with 2% [O2]. The major discoveries include: (i) cav-1 but not cav-2 was up-regulated in the cells exposed to 15 h of hypoxia; (ii) NO donor 1-[N, N-di-(2-aminoethyl) amino] diazen-1-ium-1, 2-diolate up-regulated the expression of cav-1, whereas the non-selective NOS inhibitor N(G)-nitro-L-arginine methyl ester and inducible NOS (iNOS) inhibitor 1400W each abolished the increase in cav-1 expression in the hypoxic SK-N-MC cells. These results suggest that iNOS-induced NO production contributes to the up-regulation of cav-1 in the hypoxic SK-N-MC cells. Furthermore, we studied the roles played by cav-1 in regulating NO, NOS, and apoptotic cell death in the SK-N-MC cells subjected to 15 h of hypoxic treatment. Both cav-1 transfection and cav-1 scaffolding domain peptide abolished the induction of iNOS, reduced the production of NO, and reduced the rates of apoptotic cell death in the hypoxic SK-N-MC cells. These results suggest that increased expression of cav-1 in response to hypoxic stimulation could prevent oxidative injury induced by reactive oxygen species. The interactions of cav-1, NO, and NOS could be an important signal pathway in protecting the neuroblastoma cells from oxidative injury, contributing to the hypoxic tolerance of neuroblastoma cells. 相似文献
12.
Dafeng Yang Zhousheng Yang Lei Chen Dabin Kuang Yang Zou Jie Li Xu Deng Songyuan Luo Jianfang Luo Jun He Miao Yan Guixia He Yang Deng Rong Li Qiong Yuan Yangzhao Zhou Pei Jiang Shenglan Tan 《Journal of cellular and molecular medicine》2020,24(10):5911-5925
Natural products were extracted from traditional Chinese herbal emerging as potential therapeutic drugs for treating cardiovascular diseases. This study examines the role and underlying mechanism of dihydromyricetin (DMY), a natural compound extracted from Ampelopsis grossedentata, in atherosclerosis. DMY treatment significantly inhibits atherosclerotic lesion formation, proinflammatory gene expression and the influx of lesional macrophages and CD4-positive T cells in the vessel wall and hepatic inflammation, whereas increases nitric oxide (NO) production and improves lipid metabolism in apolipoprotein E-deficient (Apoe−/−) mice. Yet, those protective effects are abrogated by using NOS inhibitor L-NAME in Apoe−/− mice received DMY. Mechanistically, DMY decreases microRNA-21 (miR-21) and increases its target gene dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression, an effect that reduces asymmetric aimethlarginine (ADMA) levels, and increases endothelial NO synthase (eNOS) phosphorylation and NO production in cultured HUVECs, vascular endothelium of atherosclerotic lesions and liver. In contrast, systemic delivery of miR-21 in Apoe−/− mice or miR-21 overexpression in cultured HUVECs abrogates those DMY-mediated protective effects. These data demonstrate that endothelial miR-21-inhibited DDAH1-ADMA-eNOS-NO pathway promotes the pathogenesis of atherosclerosis which can be rescued by DMY. Thus, DMY may represent a potential therapeutic adjuvant in atherosclerosis management. 相似文献
13.
Triptolide inhibits cyclooxygenase-2 and inducible nitric oxide synthase expression in human colon cancer and leukemia cells 总被引:1,自引:0,他引:1
Triptolide (TP),a traditional Chinese medicine,has been reported to be effective in thetreatment of autoimmune diseases and exerting antineoplastic activity in several human tumor cell lines.Thisstudy investigates the antitumor effect of TP in human colon cancer cells (SW114) and myelocytic leukemia(K562),and elucidates the possible molecular mechanism involved.SW114 and K562 cells were treatedwith different doses of TP (0,5,10,20,or 50 ng/ml).The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Results demonstrated that TP inhibited the proliferation ofboth tumor cell lines in a dose-dependent manner.To further investigate its mechanisms,the productsprostaglandin E_2 (PGE2) and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay(ELISA).Our data showed that TP strongly inhibited the production of NO and PGE_2. Consistent with theseresults,the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was up-regulatedboth at the mRNA level and the protein expression level,as shown by real-time RT-PCR and Westernblotting.These results indicated that the inhibition of the inflammatory factor COX-2 and iNOS activitycould be involved in the antitumor mechanisms of TP. 相似文献
14.
Ishii H Shibuya K Ohta Y Mukai H Uchino S Takata N Rose JA Kawato S 《Journal of neurochemistry》2006,96(6):1531-1539
The current quantitative study demonstrates that the recruitment of neuronal nitric oxide synthase (nNOS) beneath N-methyl-D-aspartate (NMDA) receptors, via postsynaptic density 95 (PSD-95) proteins significantly enhances nitric oxide (NO) production. Real-time single-cell fluorescence imaging was applied to measure both NO production and Ca(2+) influx in Chinese hamster ovary (CHO) cells expressing recombinant NMDA receptors (NMDA-R), nNOS, and PSD-95. We examined the relationship between the rate of NO production and Ca(2+) influx via NMDA receptors using the NO-reactive fluorescent dye, diaminofluorescein-FM (DAF-FM) and the Ca(2+)-sensitive yellow cameleon 3.1 (YC3.1), conjugated with PSD-95 (PSD-95-YC3.1). The presence of PSD-95 enhanced the rate of NO production by 2.3-fold upon stimulation with 100 microm NMDA in CHO1(+) cells (expressing NMDA-R, nNOS and PSD-95) when compared with CHO1(-) cells (expressing NMDA-R and nNOS lacking PSD-95). The presence of nNOS inhibitor or NMDA-R blocker almost completely suppressed this NMDA-stimulated NO production. The Ca(2+) concentration beneath the NMDA-R, [Ca(2+)](NR), was determined to be 5.4 microm by stimulating CHO2 cells (expressing NMDA-R and PSD-95-YC3.1) with 100 microm NMDA. By completely permealizing CHO1 cells with ionomycin, a general relationship curve of the rate of NO production versus the Ca(2+) concentration around nNOS, [Ca(2+)](NOS), was obtained over the wide range of [Ca(2+)](NOS). This sigmoidal curve had an EC(50) of approximately 1.2 microm of [Ca(2+)](NOS), implying that [Ca(2+)](NR) = 5.4 microm can activate nNOS effectively. 相似文献
15.
Havenga MJ van Dam B Groot BS Grimbergen JM Valerio D Bout A Quax PH 《Analytical biochemistry》2001,290(2):283-291
Nitric oxide (NO) is involved in the regulation of SMC proliferation during intimal hyperplasia as has been shown by the inhibitory effect on intimal hyperplasia of adenovirus-mediated ceNOS overexpression in injured arteries in pig. Good assays to quantify the NO-producing enzymes, i.e., NO synthases (NOS), are essential to analyze the mechanism of action of NO in this process. We have developed novel flow cytometric assays for the simultaneous detection of NOS-3 protein, using NOS-3 specific antibodies, and NO production using 4,5-diaminofluorescein-diacetate (DAF-2/DA). The presence of NOS-3 protein and NO production is demonstrated on human A549 and HepG2 cells infected with a NOS-3 adenovirus (Ad.NOS-3). A comparative study showed that the flow cytometric assays are equally sensitive as Western blot analysis, the citrulline assay, or the Sievers assay. On human endothelial and SMC, NOS-3 protein and NO production were simultaneously detected with the assays, both under basal conditions and after Ad.NOS-3transduction. Simultaneous analysis of NOS-3 protein and NO production, made possible by the here-described novel flow cytometric assays, is of significant value to those investigating NOS-3 and NO. 相似文献
16.
Furge LL Fields PR Goode WE Konwinski RR Tressler MC Stevens-Truss R 《Archives of biochemistry and biophysics》2004,424(2):163-170
The clinically relevant drug oltipraz (OPZ) has previously been shown to inhibit cytochrome P450 enzymes [Chem. Res. Toxicol. 13 (2000) 245]. The current study reveals that OPZ is also able to inhibit *NO formation by purified inducible nitric oxide synthase (iNOS) but not by neuronal nitric oxide synthase in hemoglobin assays. The inhibition of iNOS by OPZ is reversible and competitive with an IC(50) of 5.9 microM and Ki of 0.6 microM. In murine BV-2 microglial cells, an immortalized cell line that produces *NO in response to lipopolysaccharide (LPS), OPZ is able to block the formation of nitrite in LPS treated cells. The inhibitory effect of OPZ on LPS treated cells is not due to cell toxicity. Finally, treatment of cells with OPZ does not induce or suppress expression of iNOS protein as shown by Western blot analysis. 相似文献
17.
18.
Excised leaves of kidney bean (Phaseolus vulgaris) were used to investigate the mechanism of NO generation under UV-B stress. We showed that two signaling molecules, NO and
H2O2, were produced in the irradiated leaves. NO release was blocked by LNNA, an inhibitor of NOS. Application of CAT (EC 1.11.1.6)
not only effectively eliminated H2O2 in the leaves, but also inhibited the activity of NOS and the emission of NO. In contrast, treatment with exogenous H2O2 increased both of those events. Therefore, we suggest that, under UV-B stress, NO production is mediated by H2O2 through greater NOS activity. 相似文献
19.
Butein has been reported to exert anti-inflammatory effect but the possible mechanism involved is still unclear. Here, we report the inhibitory effect of butein on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) gene expression. Butein also inhibited the induction of tumor necrosis factor-alpha and cyclooxygenase 2 by LPS. To further investigate the mechanism responsible for the inhibition of iNOS gene expression by butein, we examined the effect of butein on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. The LPS-induced DNA binding activity of NF-kappaB was significantly inhibited by butein, and this effect was mediated through inhibition of the degradation of inhibitory factor-kappaB and phosphorylation of Erk1/2 MAP kinase. Furthermore, increased binding of the osteopontin alphavbeta3 integrin receptor by butein may explain its inhibitory effect on LPS-mediated NO production. Taken together, these results suggest that butein inhibits iNOS gene expression, providing possible mechanisms for its anti-inflammatory action. 相似文献
20.
The activation and deactivation of Ca2+- and calmodulindependent neuronal nitric oxide synthase (nNOS) in the central nervous system must be tightly controlled to prevent excessive nitric oxide (NO) generation. Considering plasma membrane calcium ATPase (PMCA) is a key deactivator of nNOS, the present investigation aims to determine the key events involved in nNOS deactivation of by PMCA in living cells to maintain its cellular context. Using time-resolved F?rster resonance energy transfer (FRET), we determined the occurrence of Ca2+-induced protein-protein interactions between plasma membrane calcium ATPase 4b (PMCA4b) and nNOS in living cells. PMCA activation significantly decreased the intracellular Ca2+ concentrations ([Ca2+]i), which deactivates nNOS and slowdowns NO synthesis. Under the basal [Ca2+]i caused by PMCA activation, no protein-protein interactions were observed between PMCA4b and nNOS. Furthermore, both the PDZ domain of nNOS and the PDZ-binding motif of PMCA4b were essential for the protein-protein interaction. The involvement of lipid raft microdomains on the activity of PMCA4b and nNOS was also investigated. Unlike other PMCA isoforms, PMCA4 was relatively more concentrated in the raft fractions. Disruption of lipid rafts altered the intracellular localization of PMCA4b and affected the interaction between PMCA4b and nNOS, which suggest that the unique lipid raft distribution of PMCA4 may be responsible for its regulation of nNOS activity. In summary, lipid rafts may act as platforms for the PMCA4b regulation of nNOS activity and the transient tethering of nNOS to PMCA4b is responsible for rapid nNOS deactivation. 相似文献