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991.
992.
Brucella spp. are facultative intracellular pathogens that have the ability to survive and multiply in professional and nonprofessional phagocytes, and cause abortion in domestic animals and undulant fever in humans. However, the mechanism and factors of virulence are not fully understood. In the present study, a D-alanyl-D-alanine carboxypeptidase (DAP) mutant of Brucella abortus failed to replicate in mouse macrophages and HeLa cells, and showed less virulence than the wild type in mice. Under nitric oxide (NO) stress, the growth of the DAP mutant in vitro decreased and it also had less capability to reduce NO than the wild type. Intracellular replication of the DAP mutant was partially restored by pretreatment of macrophages with the NO synthase inhibitor, 1-phenyl-imidazole, and the level of expression of the NO reductase gene, norB, in the DAP mutant was lower than that in the wild type. These results suggest that DAP contributes to resistance against NO and that it is required for the intracellular growth of the bacterium. 相似文献
993.
Mühling J Engel J Halabi M Müller M Fuchs M Krüll M Harbach H Langefeld TW Wolff M Matejec R Welters ID Menges T Hempelmann G 《Amino acids》2006,31(1):11-26
Summary. We have examined the effects of Nω-nitro-L-arginine-methylester-hydrochloride [L-NAME; inhibitor of nitric oxide synthase], S-nitroso-N-acetyl-penicillamine
[SNAP; nitric oxide donor], α-difluoro-methyl-ornithine [DFMO; inhibitor of ornithine decarboxylase] arginine or ornithine
as well as the combination of arginine or ornithine with L-NAME, SNAP or DFMO on intracellular free amino- and α-keto acid
profiles and the immune function markers superoxide anion and hydrogen peroxide generation as well as released myeloperoxidase
activity in neutrophils (PMN). Although the underlying mechanisms still remain unclear, we believe from our results that nitric
oxide as well as polyamine-dependent pathways are involved in the signal transmission of free radical molecule, beneficial
nutritional therapy or maleficient pharmacological stress-induced alterations in PMN nutrient composition. Relevant changes
in intragranulocyte free amino- and α-keto acid homeostasis and metabolism, especially, may be one of the determinants in
PMN nutrition that positively or negatively influences and modulate neutrophil host defence capability and immunocompetence. 相似文献
994.
995.
Davies NA Hodges SJ Pitsillides AA Mookerjee RP Jalan R Mehdizadeh S 《FEBS letters》2006,580(8):2123-2128
The production of nitric oxide (NO) in liver disease and its role in vascular control has been a subject of much interest in recent years. However, the activity of guanylate cyclase (GC), the enzyme activated by NO has received little attention with regard to liver disease. In this study we have utilised a quantitative cytochemical technique to examine the activity of GC on a per cell basis in a rat model of cirrhosis. Our results show a significant reduction in GC activity, indicating that vascular regulation is likely to be substantially affected irrespective of NO generation in this disease model. 相似文献
996.
Saurabh Chatterjee Sudha Premachandran Raghavendra S. Bagewadikar Sayanti Bhattacharya Subrata Chattopadhyay T.B. Poduval 《Nitric oxide》2006,15(4):408-416
We have demonstrated that therapeutic administration of L-arginine (L-arg) (120 mg/kg) at +2 h of whole body hyperthermia (WBH) could rescue the mice from heatstroke-induced death. Studies were undertaken to elucidate the role of L-arg in the immunomodulation of the heat-stressed mice. Administration of L-arginine (L-arg), (120 mg/kg, i.p.), at +2 h of WBH, rescued the mice from heat-induced death and reduced the hypothermia. At +4 and +24 h of WBH, levels of IL-1beta, IFN-gamma, nitrite, TNF-alpha, IL-4, TGF-beta1, inducible form of nitric oxide synthase (iNOS), and corticosterone significantly increased compared to the sham group. The elevated levels of Th(1) cytokines, namely TNF-alpha, IL-1beta, IFN-gamma, nitrite, and iNOS, decreased significantly both at +4 and +24 h of WBH, following L-arg administration. However, L-arg administration did not reduce the increased levels of Th(2) cytokines, namely IL-4 and TGF-beta1, in WBH mice at +4 h of WBH. L-arg administration significantly increased the levels of Th(2) cytokines at +24 h of WBH, compared to the saline-treated WBH mice. L-arg administration significantly increased both the splenic and hepatic arginase activity at +4 and +24 h of WBH compared to the saline-treated WBH mice. L-NAME treatment at +2 h of WBH and anti-TGF-beta antibody treatment at 0 h of WBH significantly increased the mortality compared to the saline-treated WBH mice. Altered liver histopathology was attenuated following the administration of L-arg at +2 h of WBH. These results suggest that therapeutic administration of L-arg at appropriate concentration and time attenuates the acute inflammatory response, leading to the rescue of mice from heatstroke. 相似文献
997.
Endothelial nitric oxide synthase genotype and haplotype are not associated with diabetic retinopathy in diabetes type 2 patients 总被引:1,自引:0,他引:1
Roger W.C. de Syllos Valeria C. Sandrim Hugo R.K. Lisboa Glaucia S. Tres Jose E. Tanus-Santos 《Nitric oxide》2006,15(4):417-422
Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene have been associated with the development of diabetic retinopathy (DR) in patients with type 1 diabetes mellitus (T1DM), but not with T2DM. However, no previous study has analyzed combinations of genetic markers (haplotypes), which can be more informative. We studied three eNOS genetic polymorphisms: a single nucleotide polymorphism in the promoter region (T(-786)C), in exon 7 (Glu298Asp), and a variable number of tandem repeats in intron 4 (b/a) in 103 healthy controls, and in 170 patients with T2DM (without DR, N=114; with DR, N=56). We also examined the association of eNOS gene haplotypes with T2DM and with DR. No differences were found in the frequencies of genotypes and alleles of the three polymorphisms among the three groups of subjects. However, the "C-Glu-b" haplotype was more common in healthy controls (24%) than in T2DM patients (7%) (P=0.0001). Finally, no significant difference in the distribution of eNOS haplotypes frequencies was found when T2DM patients with or without DR were compared (P=0.7372). These findings suggest no association between DR and individual eNOS haplotypes in T2DM patients. The "C-Glu-b" haplotype, however, may have a protective effect against T2DM. Further studies should be conducted to address the molecular basis for such an effect. 相似文献
998.
Nakhjavani M Morteza A Asgarani F Khalilzadeh O Ghazizadeh Z Bathaie SZ Esteghamati A 《Gene》2012,498(1):107-111
Background
Experimental evidence suggests that heat shock proteins (HSP) and asymmetric dimethylarginine (ADMA) are induced in the state of chronic inflammation and stress conditions. They are both inhibitors of nitric oxide synthase (NOS). The aim of this study was to evaluate the correlation between ADMA and HSP70, in patients with type 2 diabetes with respect to serum levels of C reactive protein (CRP).Methods
We quantified serum HSP70, ADMA and CRP in 80 newly-diagnosed patients with type 2 diabetes plus 80 age-, sex and BMI-matched healthy controls. The patients and controls were also stratified into groups of high and low CRP levels (cut-point: 2.5 mg/ml).Results
Patients with type 2 diabetes had significantly higher serum HSP70 (0.52 [0.51–0.66] vs. 0.27 [0.26–0.36], p < 0.001), ADMA (0.86 [0.81–0.92] vs. 0.72 [0.71–0.85], p < 0.05) and CRP (2.9 [1.7–3.4] vs. 1.6[1.2–2.3], p < 0.05) compared with healthy controls. Serum HSP70 and ADMA levels were significantly correlated in patients with high CRP levels (r = 0.89, p < 0.01), whereas there were no correlation in patients with low CRP (r = − 0.37, p = 0.07) and controls. This correlation was significant (r = 0.77, p < 0.001) in patients with high CRP and also in patients with low CRP levels (r = − 0.51, p < 0.05), after multiple adjustments for LDL and HDL levels.Discussion
We showed that, in a state of high inflammation; serum levels of ADMA parallel the HSP70 levels. However in low inflammation, they are negatively correlated. The duality in HSP70 and ADMA correlation may be related to the duality of NOS function in low and high CRP levels. 相似文献999.
Genome sequencing has shown the presence of genes coding for NO-synthase (NOS)-like proteins in bacteria. The roles and properties of these proteins remain unclear. UV-visible spectroscopy was used to characterize the recombinant NOS-like protein from Bacillus subtilis (bsNOS) in its ferric and ferrous states in the presence of various FeIII- and FeII-heme-ligands and of a series of l-arginine (l-arg) analogs. BsNOS exhibited several spectroscopic and binding properties in common with Bacillus anthracis NOS (baNOS) that were clearly different from those of tetrahydrobiopterin (H4B)-free mammalian NOS oxygenase domains (mNOSoxys) and of Staphylococcus aureus NOS (saNOS). Interestingly, bsNOS and baNOS that do not contain H4B exhibited properties much closer to those of H4B-containing mNOSoxys. Moreover, bsNOS was found to efficiently catalyze the oxidation of l-arginine into l-citrulline by H2O2, whereas H4B-free mNOSoxys exhibited low activities for this reaction. 相似文献
1000.
Glutamate is the main excitatory neurotransmitter in the retina, but it is toxic when present in excessive amounts. It is well known that NO is involved in glutamate excitotoxicity, but information regarding the possibility that NO-related species could reciprocally affect glutamate synaptic levels was not previously provided. The dependence of glutamatergic neurons upon glia via the glutamate/glutamine cycle to provide the precursor for neurotransmitter glutamate is well established. The aim of the present work was to comparatively analyze the effect of nitroxyl and NO on the retinal glutamate/glutamine cycle in vitro activity. For this purpose, Angeli's salt (AS) and diethylamine NONOate (DEA/NO) were used as nitroxyl and NO donor, respectively. AS and DEA/NO significantly decreased retinal l-glutamate uptake and glutamine synthetase activity, but only AS decreased l-glutamine influx. Dithiothreitol prevented all the effects of AS and DEA/NO. The intravitreal injection of DEA/NO (but not AS) or a supraphysiological concentration of glutamate induced retinal histological alterations. Although AS could increase glutamate synaptic concentration in vitro, the histological alterations induced by glutamate were abrogated by AS. These results suggest that nitroxyl could regulate the hamster retinal glutamatergic pathway by acting through differential mechanisms at pre- and postsynaptic level. 相似文献