Changes in endothelial nitric oxide synthase (eNOS) expression may be involved in the endothelium-dependent vasorelaxation dysfunction associated with several vascular diseases. In the present work, we demonstrate that eNOS mRNA contains a previously undescribed cis element in the 3 untranslated region (3 UTR). A U؉C-rich segment in the 3 UTR is critical in complex formation with bovine aortic endothelial cell cytosolic proteins. Tumor necrosis factor alpha (TNF-␣), which destabilizes eNOS mRNA, increased the binding activity of the cytosolic proteins in a time-dependent manner. These data suggest that endothelial cytosolic proteins bind to the 3 UTR of eNOS mRNA. These proteins may play a role in TNF-␣-induced eNOS mRNA destabilization.Nitric oxide (NO) is a gas generated by the metabolic conversion of L-arginine into L-citrulline by the activity of NOsynthesizing enzymes (NO synthases [NOS]) (23). Two major types of NOS activities have been identified in the vessels: an endothelial isoform (eNOS), which is localized in the endothelium under physiological conditions, and an inducible isoenzyme, which requires cytokines or endotoxin activation for its expression (23,29). Loss of endothelium-derived NO results in vascular abnormalities including vasoconstriction, smooth muscle cell proliferation, and adhesion of blood elements to the vessel walls (12,16,23,26
The pathogenesis of idiopathic nephrotic syndrome (minimal change nephropathy and its variants) is not completely understood. In recent years it has been speculated that a cytokine released by circulating blood mononuclear cells could alter the permeability of the glomerular capillary wall. In this study we have explored the potential participation of tumour necrosis factor alpha (TNF alpha), a cytokine mainly produced by monocytes, in 25 children with idiopathic nephrotic syndrome. TNF alpha was determined by cytotoxicity bioassay in the L-929 cell line and by double antibody/RIA. Patients in activity had higher serum TNF alpha levels and TNF alpha production by monocytes than patients in remission and controls. TNF alpha mRNA expression in blood mononuclear cells was analysed by Northern blot. The TNF alpha mRNA levels in patients in activity were increased compared to controls and to patients in remission. No significant differences in IL-1 beta and IL-6 synthesis were found between patients and controls. Our results suggest that TNF alpha, but not other cytokines such as IL-1 beta and IL-6, could play a role in the pathogenesis of the proteinuria in idiopathic nephrotic syndrome.
Background: Diarrhoeal diseases constitute a major public health problem, particularly in the developing world, where the rate of mortality and morbidity is very high. The purpose of this study was to conduct a 2 years and 3 months study in order to determine the prevalence of five enteropathogen diarrheogenic agents in Mexico City.
Our results show that myocardial ischemia/reperfusion stimulates production of NO by circulating neutrophils, an effect that was enhanced in the presence of aspirin. These results suggest a novel interpretation of the protective effect of aspirin on myocardial ischemia damage.
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