共查询到20条相似文献,搜索用时 15 毫秒
1.
Effects of simulated microgravity on nitric oxide level in cardiac myocytes and its mechanism 总被引:3,自引:0,他引:3
Prolonged exposure to space microgravity results in cardiovascular deconditioning and the depression of cardiac contractility, while its mechanism is still unknown[1]. Thus study about ef-fects of microgravity on cardiac myocytes and related mechanism is an important issue in space medicine. It would also contribute to understanding effects of mechanical signal on signal transduction in cardiac myocytes and pathology of related diseases. Nitric oxide (NO) is a universal signal molecular in ce… 相似文献
2.
Viktor Brovkovych Yongkang Zhang Svitlana Brovkovych Richard D. Minshall Randal A. Skidgel 《Journal of cellular and molecular medicine》2011,15(2):258-269
Inducible nitric oxide synthase (iNOS) is a major source of nitric oxide during inflammation whose activity is thought to be controlled primarily at the expression level. The B1 kinin receptor (B1R) post‐translationally activates iNOS beyond its basal activity via extracellular signal regulated kinase (ERK)‐mediated phosphorylation of Ser745. Here we identified the signalling pathway causing iNOS activation in cytokine‐treated endothelial cells or HEK293 cells transfected with iNOS and B1R. To allow kinetic measurements of nitric oxide release, we used a sensitive porphyrinic microsensor (response time = 10 msec.; 1 nM detection limit). B1Rs signalled through Gαi coupling as ERK and iNOS activation were inhibited by pertussis toxin. Furthermore, transfection of constitutively active mutant Gαi Q204L but not Gαq Q209L resulted in high basal iNOS‐derived nitric oxide. G‐βγ subunits were also necessary as transfection with the β‐adrenergic receptor kinase C‐terminus inhibited the response. B1R‐dependent iNOS activation was also inhibited by Src family kinase inhibitor PP2 and trans‐fection with dominant negative Src. Other ERK‐MAP kinase members were involved as the response was inhibited by dominant negative H‐Ras, Raf kinase inhibitor, ERK activation inhibitor and MEK inhibitor PD98059. In contrast, PI3 kinase inhibitor LY94002, calcium chelator 1,2‐bis‐(o‐Aminophenoxy)‐ethane‐N,N,N′,N′‐tetraacetic acid, tetraacetoxymethyl ester (BAPTA‐AM), protein kinase C inhibitor calphostin C and protein kinase C activator PMA had no effect. Angiotensin converting enzyme inhibitor enalaprilat also directly activated B1Rs to generate high output nitric oxide via the same pathway. These studies reveal a new mechanism for generating receptor‐regulated high output nitric oxide in inflamed endothelium that may play an important role in the development of vascular inflammation. 相似文献
3.
Liu W Kato M Itoigawa M Murakami H Yajima M Wu J Ishikawa N Nakashima I 《Journal of cellular biochemistry》2001,83(2):271-280
4.
Sung CS Wen ZH Chang WK Chan KH Ho ST Tsai SK Chang YC Wong CS 《Journal of neurochemistry》2005,94(3):742-752
We have reported recently that intrathecal (i.t.) injection of interleukin-1beta (IL-1beta), at a dose of 100 ng, induces inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in the spinal cord and results in thermal hyperalgesia in rats. This study further examines the role of mitogen-activated protein kinase (MAPK) in i.t. IL-1beta-mediated iNOS-NO cascade in spinal nociceptive signal transduction. All rats were implanted with an i.t. catheter either with or without an additional microdialysis probe. Paw withdrawal latency to radiant heat is used to assess thermal hyperalgesia. The iNOS and MAPK protein expression in the spinal cord dorsal horn were examined by western blot. The [NO] in CSF dialysates were also measured. Intrathecal IL-1beta leads to a time-dependent up-regulation of phosphorylated p38 (p-p38) MAPK protein expression in the spinal cord 30-240 min following IL-1beta injection (i.t.). However, neither the phosphorylated extracellular signal-regulated kinase (p-ERK) nor phosphorylated c-Jun NH2-terminal kinase (p-JNK) was affected. The total amount of p38, ERK, and JNK MAPK proteins were not affected following IL-1beta injection. Intrathecal administration of either selective p38 MAPK, or JNK, or ERK inhibitor alone did not affect the thermal nociceptive threshold or iNOS protein expression in the spinal cord. However, pretreatment with a p38 MAPK inhibitor significantly reduced the IL-1beta-induced p-p38 MAPK expression by 38-49%, and nearly completely blocked the subsequent iNOS expression (reduction by 86.6%), NO production, and thermal hyperalgesia. In contrast, both ERK and JNK inhibitor pretreatments only partially (approximately 50%) inhibited the IL-1beta-induced iNOS expression in the spinal cord. Our results suggest that p38 MAPK plays a pivotal role in i.t. IL-1beta-induced spinal sensitization and nociceptive signal transduction. 相似文献
5.
蛋白激酶C和蛋白酪氨酸激酶介导脂多糖及细胞因子诱导大鼠血管平滑肌细胞一氧化氮的生成 总被引:4,自引:0,他引:4
采用Spprague-Dawley大鼠胸主动脉中膜、外膜和培养的血管平滑肌细胞(VSMCs)作材料,鉴定不同类型的血管组织经炎性介质刺激后其一氧化氮(NO)的产生来源,闻明蛋白激酶C(PKC)和蛋白酪氨酸激酶(PTK)介导大鼠VSMCs生成NO的调控机制。大鼠VSMCs经脂多糖(LPG)和细胞因子(TNF-α,IL-1β)处理后,以剂量依赖方式促进NO释放。采用Western Blot证实经刺激的VSMCs伴有iNOS表达上调。进一步实验表明PKC和PTK参与LPS和细胞因子诱导NO生成的胞内信号转导。用PKC抑制剂H7与VSMCs共培育,H7能明显减少LPS、TNF-α和IL-1β诱导细胞NO的形成。白屈菜赤碱亦可抑制NO的生成,但HAl004对VSMCs的NO生成无抑制作用,提示PKC参与NO的生成与调控。PTK抑制剂genistein和tyrphostin AG18均能抑制由LPS、TNF-α和IL-1β引发VSMCs释放NO,同时伴iNOS蛋白表达下调,而PKC抑制剂不能阻断iNOS的表达。上述观察结果提示,PKC介导LPS和细胞因子诱导细胞合成NO可能是通过iNOS翻译后加工;而PTK则以上调iNOS表达而促增NO生成。 相似文献
6.
白细胞介素—10对血管一氧化氮/一氧化氮合酶系统的影响 总被引:5,自引:1,他引:4
为探讨抗炎因子--白细胞介素-10(IL-10)对大鼠主动脉一氧化氮(NO)/一氧化氮合酶(NOS)系统的影响,应用Griess试剂、^3H-瓜氨酸生成及蛋白免疫印迹杂交等方法,测定IL-10孵育对血管NO释放、NOS活性及表达的影响。结果发现细菌脂多糖(LPS)呈浓度领带性地激活诱导型NOS(iNOS),促进NO生成。IL-10(10^-10-10^-8g/ml)呈浓度依赖性地上调内皮型NOS(eNOS)蛋白表达及其活性,但对iNOS活性及表达无明显影响,IL-10(10^-9-10^-8g/ml)显著抑制10μg/ml LPS诱导的NO生成和iNOS激活;而高浓度IL-10(10^-7g/ml)则上调iNOS的活性,对eNOS蛋白的表达知活性无明显影响。因此IL-10对NO/NOS系统具有双重影响,一方面可抑制炎症介质诱发的作为炎性物质的iNOS的表达及激活,另一方面可上调内皮源扩血管物质NO的释放。 相似文献
7.
Nitric oxide down-regulates caveolin-1 expression in rat brains during focal cerebral ischemia and reperfusion injury 总被引:1,自引:0,他引:1
Shen J Ma S Chan P Lee W Fung PC Cheung RT Tong Y Liu KJ 《Journal of neurochemistry》2006,98(4):1078-1089
As a signalling molecule of the integral membrane protein family, caveolin participates in cellular signal transduction via interaction with other signalling molecules. The nature of interaction between nitric oxide (NO) and caveolin in the brain, however, remains largely unknown. In this study we investigated the role(s) of NO in regulating caveolin-1 expression in rat ischemic brains with middle cerebral artery occlusion (MCAO). Exposure to 1 h ischemia induced the increases in neuronal nitric oxide synthase (nNOS) and NO concentration with concurrent down-regulation of caveolin-1 expression in the ischemic core of rat brains. Subsequent 24 h or more reperfusion time led to an increase in inducible NOS (iNOS) expression and NO production, as well as a decline of caveolin-1 protein at the core and penumbra of the ischemic brain. Afterwards, NOS inhibitors and an NO donor were utilized to clarify the link between NO production and caveolin-1 expression in the rats with 1 h ischemia plus 24 h reperfusion. N(G)-nitro-l-arginine methyl ester (L-NAME, a non-selective NOS inhibitor), N(6)-(1-iminoethyl)-lysine (NIL, an iNOS inhibitor), and 7-nitroindazole (7-NI, a nNOS inhibitor) prevented the loss of caveolin-1 in the core and penumbra of the ischemic brain, whereas l-N(5)-(1-iminoethyl)-ornithine (L-NIO, an endothelial NOS inhibitor) showed less effect than the other NOS inhibitors. S-Nitroso-N-acetylpenicillamine (SNAP, a NO donor) down-regulated the expression of caveolin-1 protein in normal and ischemic brains. These results, when taken together, suggest that NO modulates the expression of caveolin-1 in the brain and that the loss of caveolin-1 is associated with NO production in the ischemic brain. 相似文献
8.
Interleukin (IL)-6 decreases cardiac contractility via a nitric oxide (NO)-dependent pathway. However, mechanisms underlying IL-6-induced NO production remain unclear. JAK2/STAT3 and ERK1/2 are two well known signaling pathways activated by IL-6 in non-cardiac cells. However, these IL-6-activated pathways have not been identified in adult cardiac myocytes. In this study, we identified activation of these two pathways during IL-6 stimulation and examined their roles in IL-6-induced NO production and decrease in contractility of adult ventricular myocytes. IL-6 increased phosphorylation of STAT3 (at Tyr(705)) and ERK1/2 (at Tyr(204)) within 5 min that peaked at 15-30 min and returned to basal levels at 2 h. Phosphorylation of STAT3 was blocked by genistein, a protein tyrosine kinase inhibitor, and AG490, a JAK2 inhibitor, but not PD98059, an ERK1/2 kinase inhibitor. The phosphorylation of ERK1/2 was blocked by PD98059 and genistein but not AG490. Furthermore, IL-6 enhanced de novo synthesis of iNOS protein, increased NO production, and decreased cardiac contractility after 2 h of incubation. These effects were blocked by genistein and AG490 but not PD98059. We conclude that IL-6 activated independently the JAK2/STAT3 and ERK1/2 pathways, but only JAK2/STAT3 signaling mediated the NO-associated decrease in contractility. 相似文献
9.
内皮型与神经型一氧化氮合酶(eNOS,nNOS)在心肌细胞内持续表达,而细胞应激可引起诱导型NOS(iNOS)表达.心肌细胞结构型eNOS与nNOS源性NO,在生理条件下对心肌主要发挥4方面的抑制作用:减缓心肌细胞搏动频率,轻度抑制心肌细胞收缩功能,加速心肌细胞舒张并增加顺应性,以及轻度抑制线粒体电子传递而增强氧利用效... 相似文献
10.
Yong‐Chun Wang Shu Zhang Ting‐Yuan Du Bing Wang Xi‐Qing Sun 《Journal of cellular biochemistry》2009,107(2):357-363
Alterations of nitric oxide contribute to post‐flight orthostatic intolerance. The aim of this study was to investigate the changes of inducible nitric oxide synthase (iNOS) and the mechanisms underlying regulation of iNOS by simulated microgravity in human umbilical vein endothelial cells (HUVECs). Clinorotation, a simulated‐model of microgravity, increased iNOS expression and promoter activity in HUVECs. The transactivations of NF‐κB and AP‐1 were suppressed by 24 h clinorotation. A key role for AP‐1, but not NF‐κB in the regulation of iNOS was shown. (1) PDTC, a NF‐κB inhibitor, had no effect on clinorotation upregulation of iNOS. (2) SP600125, a JNK‐specific inhibitor, which resulted in inhibition of AP‐1 activity, enhanced the iNOS expression and promoter activity in clinorotation. (3) Overexpression of AP‐1 remarkably attenuated the upregulation effect of clinorotation. These findings indicate that clinorotation upregulates iNOS in HUVECs by a mechanism dependent on suppression of AP‐1, but not NF‐κB. These results support a key role for AP‐1 in the signaling of postflight orthostatic intolerance. J. Cell. Biochem. 107: 357–363, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
11.
Luo CX Zhu XJ Zhou QG Wang B Wang W Cai HH Sun YJ Hu M Jiang J Hua Y Han X Zhu DY 《Journal of neurochemistry》2007,103(5):1872-1882
Nitric oxide (NO), a free radical with signaling functions in the CNS, is implicated in some developmental processes, including neuronal survival, precursor proliferation, and differentiation. However, neuronal nitric oxide synthase (nNOS) -derived NO and inducible nitric oxide synthase (iNOS) -derived NO play opposite role in regulating neurogenesis in the dentate gyrus after cerebral ischemia. In this study, we show that focal cerebral ischemia reduced nNOS expression and enzymatic activity in the hippocampus. Ischemia-induced cell proliferation in the dentate gyrus was augmented in the null mutant mice lacking nNOS gene (nNOS−/−) and in the rats receiving 7-nitroindazole, a selective nNOS inhibitor, after stroke. Inhibition of nNOS ameliorated ischemic injury, up-regulated iNOS expression, and enzymatic activity in the ischemic hippocampus. Inhibition of nNOS increased and iNOS inhibitor decreased cAMP response element-binding protein phosphorylation in the ipsilateral hippocampus in the late stage of stroke. Moreover, the effects of 7-nitroindazole on neurogenesis after ischemia disappeared in the null mutant mice lacking iNOS gene (iNOS−/−). These results suggest that reduced nNOS is involved in ischemia-induced hippocampal neurogenesis by up-regulating iNOS expression and cAMP response element-binding protein phosphorylation. 相似文献
12.
Viviane El-Helou Samar Bel-Hadj Jessica Drapeau Robert Clement Hugues Gosselin Angelino Calderone 《Nitric oxide》2006,14(4):316-326
The antiproliferative action of nitric oxide (NO) has been well established and increased production was reported in the infarcted rat heart. Concomitantly, increased DNA synthesis and hyperplasia of cardiac myocytes were documented in the hypertrophied myocardium. Despite these observations, the effect of NO on DNA synthesis in hypertrophied cardiac myocytes remains unexamined. Hypertrophy of the non-infarcted left ventricle (NILV) in 1-week post-MI rats was characterized by the increased prepro-ANP and reduction of alpha-myosin heavy chain protein expression. Inducible NO synthase was expressed in the NILV and associated with a concomitant attenuation of MnSuperoxide dismutase protein content. The latter data suggest that an antiproliferative action of NO in the hypertrophied NILV may proceed via either a cyclic GMP-dependent pathway and/or facilitated by a peroxynitrite-dependent mechanism. In neonatal rat ventricular myocytes (NNVM), the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) promoted a dose-dependent attenuation of DNA synthesis via a cyclic GMP-independent pathway. The permeable superoxide dismutase mimetic and peroxynitrite scavenger MnTBAP abrogated SNAP-dependent attenuation of DNA synthesis in NNVM. MnTBAP failed to inhibit SNAP-mediated recruitment of extracellular signal regulated kinase 1/2 (ERK1/2) but partially attenuated p38 phosphorylation. In hypertrophied NNVM induced by norepinephrine, SNAP-mediated peroxynitrite-dependent inhibition of DNA synthesis, ERK1/2 and p38 phosphorylation were significantly attenuated. Collectively, these data suggest that despite a favourable environment for NO and subsequent peroxynitrite generation in the NILV, hypertrophied cardiac myocytes may be partially refractory to their biological actions. 相似文献
13.
14.
诱导型一氧化氮合酶在17β-雌二醇诱导的血管平滑肌细胞周期阻滞中的作用 总被引:5,自引:0,他引:5
利用大鼠血管平滑肌细胞(vascular smooth muscle cells,VSMC)作为模型,观察17β-雌二醇(17β-estradiol,E2)对VSMC诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)活性和蛋白表达的影响,并探讨其在内皮素-1(endothlin 1,ET-1)刺激的VSMC周期循环中的作用。检测指标包括同位素法测定iNOS的活性,免疫印迹法(western blot)检测iNOS蛋白表达,流式细胞仪检测细胞周期,观察一氧化氮合酶(nitric oxide synthase,NOS)抑制剂N^G-硝基左旋精氨酸甲酯(N^G-nitro—L—arginine methylester,L—NAME)对E2抑制VSMC细胞周期的影响。结果显示,E2明显增加iNOS的活性和蛋白表达,在30min和12h时能诱导VSMC的iNOS活性明显增加,而60min和24h时VSMC的iNOS活性与对照组无显著差异,不呈明显浓度依赖性,雌激素受体(estrogen receptor,ER)拮抗剂Tamoxifen和L—NAME能明显抑制E2诱导的VSMC iNOS活性增加;E2增加VSMC的iNOS蛋白表达的作用在3h时起效,12h达高峰,以后逐渐下降,呈浓度依赖性,Tamoxifen能明显抑制马诱导的VSMC iNOS蛋白表达;E2明显抑制ET-1诱导的S期细胞百分比和G2 S/G1增加,使VSMC在G1期发生细胞周期阻滞,这些作用可被预先给予L—NAME所明显减轻。上述结果提示,E2使ET—l刺激的VSMC细胞周期循环在G1期发生阻滞与增加VSMC iNOS活性有关,该作用至少部分通过ER介导。 相似文献
15.
Penehyclidine hydrochloride attenuates LPS-induced iNOS production by inhibiting p38 MAPK activation in endothelial cells 总被引:1,自引:0,他引:1
The aim of this study was to investigate the inhibitory effect of penehyclidine hydrochloride (PHC) on lipopolysaccharide
(LPS)-induced nitric oxide (NO) and inducible nitric oxide synthase (iNOS) production in human endothelial cell. Cultured
endothelial cells were pretreated with PHC, followed by LPS treatment. NO activity were determined. iNOS expression and p38
mitogen-activated protein kinase (p38 MAPK) protein expression were measured by Western blot analysis. LPS treatment significantly
induced p38 MAPK activation, iNOS expression, and NO production, which could be attenuated by 2 μg/ml PHC pretreatment. Furthermore,
our study showed LPS-induced NO production and iNOS expression were suppressed by p38 MAPK inhibitor SB203580 pretreatment.
We concluded that PHC attenuates NO production and iNOS expression by suppressing the activation of p38 MAPK pathway, thereby
implicating a mechanism by which PHC may exert its protective effects against LPS-induced endothelial cell injury. 相似文献
16.
MAPK信号途径在一氧化氮抑制大鼠心肌肥大中的作用 总被引:31,自引:0,他引:31
实验观察了一氧化氮(NO)前体L-精氨酸对肾性高血压大鼠心肌组织eNOS蛋白表达及亚硝酸盐/硝酸盐含量、MKP-1蛋白表达及MAPK活性的影响,以及与心肌肥厚的关系,采用两肾一夹Goldblatt肾性高血压模型,随机分为5组:L-精氨酸高、中、低剂量组,分别于术后第5周给予L-精氨酸50、150及450mg/kg;L-NAME组,腹腔注射L-NAME 10mg/kg,同时给予L-精氨酸150mg/kg;高血压对照组,正常饮水,以及另设的一假手术对照组。用药8周后,用插管法测量大鼠动脉血压、左心室重与体重比值,用胶内原位磷酸化法测MFAPK活性、免疫印迹法检测心肌组织eNOS及MKP-1蛋白表达、酶还原法测定心肌组织亚硝酸盐/硝酸盐-硝酸盐含量。结果表明:(1)L-精氨酸可明显抑制肾动脉狭窄术后的血压升高、左心室重与体重比增加,增加心肌组织eNOS、MKP-1蛋白表达及亚硝酸盐-硝酸盐含量,降低心肌组织MAPK活性,其中以150mg/kg组作用最为明显;(2)NOS抑制剂L-NAME可明显抑制-精氨酸的以上作用,肾性高血压大鼠心肌组织eNOS蛋白表达下降。NO生成减少及MKP-1蛋白表达下降以及MAPK活性增强可能与高血压及心肌厚形成有关,L-精氨酸通过促进心肌组织eNOS蛋白表达、增加NO产生和MKP-1表达、减弱MAPK活性而发挥抗高血压及心肌肥厚的作用。 相似文献
17.
Trichosanthin inhibits antigen-specific T cell expansion through nitric oxide-mediated apoptosis pathway 总被引:8,自引:0,他引:8
Trichosanthin (TCS) has been found to exhibit inflammation-suppressing effect but the underlying mechanisms are not clear. In this study, we found that TCS inhibited OVA-specific T cell proliferation in a dose-dependent manner. Such inhibition was correlated with enhanced cell death. At the same time, inducible nitric oxide synthase (iNOS) mRNA expression and protein levels were found increased in cells treated with TCS, and nitric oxide (NO) production by cells was elevated in the presence of TCS. When L-NIL, the specific inhibitor of iNOS, was added to suppress NO production induced by TCS, OVA-specific cell death was significantly inhibited, meanwhile, thymidine incorporation of cells was rescued towards normal levels. These results indicate that TCS could inhibit antigen-specific T cell activation via NO-mediated apoptosis pathway. 相似文献
18.
Ionova IA Vásquez-Vivar J Whitsett J Herrnreiter A Medhora M Cooley BC Pieper GM 《American journal of physiology. Heart and circulatory physiology》2008,295(5):H2178-H2187
Adult rat cardiac myocytes typically display a phenotypic response to cytokines manifested by low or no increases in nitric oxide (NO) production via inducible NO synthase (iNOS) that distinguishes them from other cell types. To better characterize this response, we examined the expression of tetrahydrobiopterin (BH4)-synthesizing and arginine-utilizing genes in cytokine-stimulated adult cardiac myocytes. Intracellular BH4 and 7,8-dihydrobiopterin (BH2) and NO production were quantified. Cytokines induced GTP cyclohydrolase and its feedback regulatory protein but with deficient levels of BH4 synthesis. Despite the induction of iNOS protein, cytokine-stimulated adult cardiac myocytes produced little or no increase in NO versus unstimulated cells. Western blot analysis under nonreducing conditions revealed the presence of iNOS monomers. Supplementation with sepiapterin (a precursor of BH4) increased BH4 as well as BH2, but this did not enhance NO levels or eliminate iNOS monomers. Similar findings were confirmed in vivo after treatment of rat cardiac allograft recipients with sepiapterin. It was found that expression of dihydrofolate reductase, required for full activity of the salvage pathway, was not detected in adult cardiac myocytes. Thus, adult cardiac myocytes have a limited capacity to synthesize BH4 after cytokine stimulation. The mechanisms involve posttranslational factors impairing de novo and salvage pathways. These conditions are unable to support active iNOS protein dimers necessary for NO production. These findings raise significant new questions about the prevailing understanding of how cytokines, via iNOS, cause cardiac dysfunction and injury in vivo during cardiac inflammatory disease states since cardiac myocytes are not a major source of high NO production. 相似文献
19.
In the infarcted rat heart, the increase of NO occurs in the hypertrophied myocardium of non-infarcted areas and its antihypertrophic
efficacy has been well established. As another endogenous regulator and the reliable index of heart pathology, B-type natriuretic
peptide also exhibits the antihypertrophic properties in many tissues by elevating intracellular cGMP. Several studies indicate
that natriuretic peptides family may exert some actions in part via a nitric oxide pathway following receptor-mediated stimulation
of iNOS. Therefore, it raises our great interest to ask what role NO plays in the antihypertrophic actions of B-type natriuretic
peptide in cardiomyocytes. Incubation of cardiomyocytes under mild hypoxia for 12 h caused a significant increase in cellular
protein content, protein synthesis and cell surface sizes. This growth stimulation was suppressed by exogenous B-type natriuretic
peptide in a concentration dependent manner. Furthermore, the generation of intracellular cGMP, the upregulation of iNOS mRNA
expression, the increase of iNOS activity and subsequent nitrite generation in hypertrophic cardiomyocytes was also increased
by B-type natriuretic peptide. AG, a selective iNOS inhibitor, inhibited the upregulation of iNOS expression and the increase
of iNOS activity by the combination of B-type natriuretic peptide/mild hypoxia or by the combination of 8-bromo-cGMP/mild
hypoxia. Rp-8-br-cGMP, cGMP dependent protein kinase inhibitor, attenuated the actions of B-type natriuretic peptide and 8-bromo-cGMP
which increases intracellular cGMP independent of B-type natriuretic peptide. In conclusion, our present data suggest that
B-type natriuretic peptide exerted the antihypertrophic effects in cardiomyocytes, which was partially attributed to induction
of iNOS-derived NO by cGMP pathway. 相似文献
20.
Background. Nitric oxide (NO) generated by nitric oxide synthase (NOS) is known to be an important modulator of the mucosal inflammatory response. In this study, we questioned whether Helicobacter pylori infection could up‐regulate the epithelial cell inducible NOS (iNOS) gene expression and whether NO production could show polarity that can be regulated by immune mediators. Materials and Methods. Human gastric epithelial cell lines were infected with H. pylori, and the iNOS mRNA expression was assessed by quantitative RT‐PCR. NO production was assayed by determining nitrite/nitrate levels in culture supernatants. To determine the polarity of NO secretion by the H. pylori‐infected epithelial cells, Caco‐2 cells were cultured as polarized monolayers in transwell chambers, and NO production was measured. Results. iNOS mRNA levels were significantly up‐regulated in the cells infected with H. pylori, and expression of iNOS protein was confirmed by Western blot analysis. Increased NO production in the gastric epithelial cells was seen as early as 18 hours postinfection, and reached maximal levels by 24 hours postinfection. The specific MAP kinase inhibitors decreased H. pylori‐induced iNOS and NO up‐regulation. After H. pylori infection of polarized epithelial cells, NO was released predominantly into the apical compartment, and IL‐8 was released predominantly into basolateral compartment. The addition of IFN‐γ to H. pylori‐infected polarized epithelial cells showed a synergistically higher apical and basolateral NO release. Conclusion. These results suggest that apical NO production mediated by MAP kinase in H. pylori‐infected gastric epithelial cells may influence the bacteria and basolateral production of NO and IL‐8 may play a role in the tissue inflammation. 相似文献