Testosterone production in mice lacking inducible nitric oxide synthase expression is sensitive to restraint stress

2007 ◽  
Vol 292 (2) ◽  
pp. E615-E620 ◽  
Author(s):  
Ben A. Weissman ◽  
Chantal M. Sottas ◽  
Ping Zhou ◽  
Costantino Iadecola ◽  
Matthew P. Hardy
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Restraint Stress ◽  
Immobilization Stress ◽  
Male Mice ◽  
Wild Type ◽  
Basal Plasma ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Immobilization stress (IMO) induces a rapid increase in glucocorticoid secretion [in rodents, corticosterone CORT)] and this is associated with decreased circulating testosterone (T) levels. Nitric oxide (NO), a reactive free radical and neurotransmitter, has been reported to be produced at higher rates in tissues such as brain during stress. The biosynthesis of T is also known to be dramatically suppressed by NO. Specifically, the inducible isoform of nitric oxide synthase (iNOS) was directly implicated in this suppression. To assess the respective roles of CORT and NO in stress-mediated inhibition of T production, adult wild-type (WT) and inducible nitric oxide synthase knockout (iNOS−/−) male mice were evaluated. Animals of each genotype were assigned to either basal control or 3-h IMO groups. Basal plasma and testicular T levels were equivalent in both genotypes, whereas testicular weights of mutant mice were significantly higher compared with WT animals. Exposure to 3-h IMO increased plasma CORT and decreased T concentrations in mice of both genotypes. Testicular T levels were also affected by stress in WT and mutant males, being sharply reduced in both genotypes. However, the concentrations of nitrite and nitrate, the stable metabolites of NO measured in testicular extracts, did not differ between control and stressed WT and iNOS−/− mice. These results support the hypothesis that CORT, but not NO, is a plausible candidate to mediate rapid stress-induced suppression of Leydig cell steroidogenesis.

scholarly journals Inducible Nitric Oxide Synthase Is Not Essential for Control of Trypanosoma cruzi Infection in Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 4081-4089 ◽  
Author(s):  
Kara L. Cummings ◽  
Rick L. Tarleton
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Trypanosoma Cruzi ◽  
Inducible Nitric Oxide Synthase ◽  
Interleukin 1 ◽  
Mouse Strains ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Immune control of many intracellular pathogens, including Trypanosoma cruzi, is reported to be dependent on the production of nitric oxide. In this study, we show that mice deficient in inducible nitric oxide synthase (iNOS or NOS2) exhibit resistance to T. cruzi infection that is comparable to that of wild-type mice. This is the case for two iNOS-deficient mouse strains, Nos2tm1Lau and Nos2 N5, infected with the Brazil or Tulahuen strain of T. cruzi. In all cases, blood parasitemia, tissue parasite load, and survival rates are similar between wild-type and iNOS-deficient mice. In contrast, both wild-type and Nos2tm1Lau mice died within 32 days postinfection when treated with the nitric oxide synthase inhibitor aminoguanidine. Increased transcription of NOS1 or NOS3 is not found in iNOS-knockout (KO) mice, indicating that the absence of nitric oxide production through iNOS is not compensated for by increased production of other NOS isoforms. However, Nos2tm1Lau mice exhibit enhanced expression of tumor necrosis factor alpha, interleukin-1, and macrophage inflammatory protein 1α compared to that of wild-type mice, and these alterations may in part compensate for the lack of iNOS. These results clearly show that iNOS is not required for control of T. cruzi infection in mice.

scholarly journals Targeted Disruption of Inducible Nitric Oxide Synthase Protects Against Aging, S-Nitrosation, and Insulin Resistance in Muscle of Male Mice

Diabetes ◽  
2012 ◽  
Vol 62 (2) ◽  
pp. 466-470 ◽  
Author(s):  
E. R. Ropelle ◽  
J. R. Pauli ◽  
D. E. Cintra ◽  
A. S. da Silva ◽  
C. T. De Souza ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Male Mice ◽  
Targeted Disruption ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

scholarly journals Both Inducible Nitric Oxide Synthase and NADPH Oxidase Contribute to the Control of Virulent Phase I Coxiella burnetii Infections

2004 ◽  
Vol 72 (11) ◽  
pp. 6666-6675 ◽  
Author(s):  
Robert E. Brennan ◽  
Kasi Russell ◽  
Guoquan Zhang ◽  
James E. Samuel
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cell Lines ◽  
Inducible Nitric Oxide Synthase ◽  
Coxiella Burnetii ◽  
Wild Type ◽  
Primary Mouse ◽  
Ifn Γ ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Host control of Coxiella burnetii infections is believed to be mediated primarily by activated monocytes/macrophages. The activation of macrophages by cytokines leads to the production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) that have potent antimicrobial activities. The contributions of ROI and RNI to the inhibition of C. burnetii replication were examined in vitro by the use of murine macrophage-like cell lines and primary mouse macrophages. A gamma interferon (IFN-γ) treatment of infected cell lines and primary macrophages resulted in an increased production of nitric oxide (NO) and hydrogen peroxide (H2O2) and a significant inhibition of C. burnetii replication. The inhibition of replication was reversed in the murine cell line J774.16 upon the addition of either the inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-l-arginine (NGMMLA) or the H2O2 scavenger catalase. IFN-γ-treated primary macrophages from iNOS−/− and p47phox−/− mice significantly inhibited replication but were less efficient at controlling infection than IFN-γ-treated wild-type macrophages. To investigate the contributions of ROI and RNI to resistance to infection, we performed in vivo studies, using C57BL/6 wild-type mice and knockout mice lacking iNOS or p47phox. Both iNOS−/− and p47phox−/− mice were attenuated in the ability to control C. burnetii infection compared to wild-type mice. Together, these results strongly support a role for both RNI and ROI in the host control of C. burnetii infection.

Effects of p38MAPK isoforms on renal mesangial cell inducible nitric oxide synthase expression

2004 ◽  
Vol 286 (1) ◽  
pp. C145-C152 ◽  
Author(s):  
Paul Lui ◽  
Chenbo Zeng ◽  
Stephen Acton ◽  
Steven Cok ◽  
Alison Sexton ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Inos Expression ◽  
Chimeric Proteins ◽  
Wild Type ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Several related isoforms of p38MAPK have been identified and cloned in many species. Although they all contain the dual phosphorylation motif TGY, the expression of these isoforms is not ubiquitous. p38α and -β2 are ubiquitously expressed, whereas p38γ and -δ appear to have more restricted expression. Because there is evidence for selective activation by upstream kinases and selective preference for downstream substrates, the functions of these conserved proteins is still incompletely understood. We have demonstrated that the renal mesangial cell expresses the mRNA for all the isoforms of p38MAPK, with p38α mRNA expressed at the highest level, followed by p38γ and the lowest levels of expression by p38β2 and -δ. To determine the functional effects of these proteins on interleukin (IL)-1β-induced inducible nitric oxide synthase (iNOS) expression, we transduced TAT-p38 chimeric proteins into renal mesangial cells and assessed the effects of wild-type and mutant p38 isoforms on ligand induced iNOS expression. We show that whereas p38γ and -δ had minimal effects on iNOS expression, p38α and -β2 significantly altered its expression. p38α mutant and p38β2 wild-type dose dependently inhibited IL-1β-induced iNOS expression. These data suggest that p38α and β2 have reciprocal effects on iNOS expression in the mesangial cell, and these observations may have important consequences for the development of selective inhibitors targeting the p38MAPK family of proteins.

scholarly journals Antimicrobial Actions of the Nadph Phagocyte Oxidase and Inducible Nitric Oxide Synthase in Experimental Salmonellosis. II. Effects on Microbial Proliferation and Host Survival in Vivo

2000 ◽  
Vol 192 (2) ◽  
pp. 237-248 ◽  
Author(s):  
Pietro Mastroeni ◽  
Andrés Vazquez-Torres ◽  
Ferric C. Fang ◽  
Yisheng Xu ◽  
Shahid Khan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Host Resistance ◽  
Wild Type ◽  
Phagocyte Oxidase ◽  
Microbial Proliferation ◽  
Bacterial Replication ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The roles of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (iNOS) in host resistance to virulent Salmonella typhimurium were investigated in gp91phox−/−, iNOS−/−, and congenic wild-type mice. Although both gp91phox−/− and iNOS−/− mice demonstrated increased susceptibility to infection with S. typhimurium compared with wild-type mice, the kinetics of bacterial replication were dramatically different in the gp91phox−/− and iNOS−/− mouse strains. Greater bacterial numbers were present in the spleens and livers of gp91phox−/− mice compared with C57BL/6 controls as early as day 1 of infection, and all of the gp91phox−/− mice succumbed to infection within 5 d. In contrast, an increased bacterial burden was detected within reticuloendothelial organs of iNOS−/− mice only beyond the first week of infection. Influx of inflammatory CD11b+ cells, granuloma formation, and serum interferon γ levels were unimpaired in iNOS−/− mice, but the iNOS-deficient granulomas were unable to limit bacterial replication. The NADPH phagocye oxidase and iNOS are both required for host resistance to wild-type Salmonella, but appear to operate principally at different stages of infection.

scholarly journals Trypanosoma congolenseInfections: Induced Nitric Oxide Inhibits Parasite Growth In Vivo

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Wenfa Lu ◽  
Guojian Wei ◽  
Wanling Pan ◽  
Henry Tabel
Keyword(s):  
Nitric Oxide ◽  
Cell Cycle ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Trypanosoma Congolense ◽  
Parasite Growth ◽  
Wild Type ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Wild-type (WT) C57BL/6 mice infected intraperitoneally with5×106Trypanosoma congolensesurvive for more than 30 days. C57BL/6 mice deficient in inducible nitric oxide synthase (iNOS−/−) and infected with 103or5×106parasites do not control the parasitemia and survive for only14±7or6.8±0.1days, respectively. Bloodstream trypanosomes of iNOS−/−mice infected with5×106  T. congolensehad a significantly higher ratio of organisms in the S+G2+M phases of the cell cycle than trypanosomes in WT mice. We have reported that IgM anti-VSG-mediated phagocytosis ofT. congolenseby macrophages inhibits nitric oxide (NO) synthesis via CR3 (CD11b/CD18). Here, we show that during the first parasitemia, but not at later stages of infection,T. congolense-infected CD11b−/−mice produce more NO and have a significantly lower parasitemia than infected WT mice. We conclude that induced NO contributes to the control of parasitemia by inhibiting the growth of the trypanosomes.

Inducible Nitric Oxide Synthase Plays a Stimulatory Role in Platelet Activation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1650-1650 ◽  
Author(s):  
Jasna A. Marjanovic ◽  
Aleksandra Stojanovic ◽  
Viktor Brovkovych ◽  
Randal A. Skidgel ◽  
Xiaoping Du
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Platelet Activation ◽  
Inducible Nitric Oxide Synthase ◽  
Knockout Mice ◽  
No Production ◽  
Wild Type ◽  
Oxide Synthase ◽  
Specific Inhibitors ◽  
Inducible Nitric Oxide

Abstract Platelets generate nitric oxide (NO) in response to agonist stimulation. Previous reports have shown that the endothelial nitric oxide synthase (eNOS) plays a role in agonist-stimulated platelet NO production and in platelet activation. Here we show that platelets from eNOS knockout mice (eNOS−/−) showed only partial reduction in thrombin-induced NO production compared to wild type platelets (50% reduction), indicating the presence of another NOS isoform in platelets. More importantly, we show that resting platelets express functional inducible nitric oxide synthase (iNOS), which participates in platelet activation. Compared to wild type platelets, thrombin-induced NO production was reduced by 54% in platelets isolated from iNOS knockout mice (iNOS−/−), indicating an iNOS-dependent NO production in platelets induced by thrombin. Since thrombin-induced NO production occurs during the first 3 min of thrombin stimulation, our findings provide the first evidence for a short-term regulation of iNOS activity independent of transcription regulation. In contrast, previous description of iNOS activation was primarily at the transcriptional level and required much longer time of induction. To determine the role of iNOS in platelet activation, platelets from wild type and iNOS−/− mice were stimulated with low concentrations of agonists. iNOS−/− platelets exhibited lower aggregation and secretion response compared to wild type control, indicating that iNOS plays a stimulatory role in platelet activation. We also examined the effect of iNOS inhibitors on platelet activation. Human and mouse platelets preincubated with iNOS specific inhibitors, 1400W and aminoguanidine, exhibited a dose-dependent inhibition of platelet secretion and aggregation induced by either low-dose thrombin or collagen. Furthermore, the inhibitory effect of iNOS-specific inhibitors was only shown in wild type mouse platelets, but was lacking in iNOS−/− platelets. Thus, activation of both iNOS and eNOS is important in agonist-induced NO production which stimulates platelet secretion and aggregation.

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