Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO) has been implicated in the induction of proteinuria in acute inflammatory glomerulonephritis and in the increased vascular permeability seen in various other disease conditions. The complicated interactions of NO with other factors in vivo hinder analysis of the mechanisms involved. By use of a recently introduced method for measuring albumin permeability (P(a)) in isolated glomeruli, the question of whether NO has a direct effect on the permeability barrier of glomerular tufts was examined and the potential mechanisms were explored. Exposure of isolated glomeruli to three NO donors, s-nitroso-N-acetyl-penicillamine (SNAP), (Z)-1-[-2-(aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate), and sodium nitroprusside, all increased the P(a). This action of NO was time- and concentration-dependent and could be mimicked by 8-bromoguanosine 3', 5'-cyclic monophosphate. Western blot analysis of the proteins from NO donor-treated glomeruli revealed an increase of phosphotyrosine levels of proteins of molecular mass about 120 and 70 kD. The demonstration that pretreatment of glomeruli with the tyrosine kinase inhibitor, genistein, could largely prevent the effect of SNAP and DETA-NONOate confirmed the crucial role of tyrosine phosphorylation in the NO-induced increase of P(a). Furthermore, the tyrosine phosphatase inhibitor, phenylarsine oxide (PAO), could mimic the action of NO on P(a). NO-enhanced tyrosine phosphorylation was further confirmed by immunofluorescence staining, where positive cells in SNAP- and PAO-treated glomeruli were much more frequent than that in controls. By use of dual-label staining in combination with podocyte specific marker, nephrin, it was observed that most of the phosphorylated positive cells corresponded to podocytes. These results suggest that NO impairs the glomerular permeability barrier through a tyrosine phosphorylation-dependent mechanism.
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PMID:Nitric oxide increases albumin permeability of isolated rat glomeruli via a phosphorylation-dependent mechanism. 1172 30

In glomerular immune injury, the inducible isoform of nitric oxide synthase (iNOS) becomes a major catalyst of NO production. Although iNOS-catalyzed NO production is sustained and can be cytotoxic, iNOS inhibition exacerbates the magnitude of proteinuria that accompanies immune injury. To investigate putative mechanisms of this effect, we assessed changes in glomerular permeability to albumin by using the following two approaches: (i) an in vivo rat model of glomerular immune injury induced by antibody against the glomerular basement membrane (GBM), in which urine albumin excretion was measured under conditions of iNOS inhibition, and (ii) an ex vivo model of isolated rat glomeruli, in which changes in glomerular capillary permeability to albumin were assessed under conditions of NOS inhibition. In rats with anti-GBM antibody-induced glomerular injury, there was an increase in urine albumin excretion. Treatment with two structurally dissimilar iNOS inhibitors at doses sufficient to decrease urine nitrate and/or nitrite exacerbated proteinuria. In these animals, urine excretion of the isoprostane 8-iso-PGF2alpha (marker of oxidative stress) was increased. In isolated glomeruli incubated with the NOS inhibitor L-NMMA, the permeability to albumin increased. This effect was reversed by the NO donor DETA NONOate and by the superoxide dismutase mimetic Tempol. We conclude that NOS-catalyzed NO production is an important mechanism in regulating glomerular permeability to protein. This mechanism involves control of the bioavailability of superoxide.
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PMID:Effect of nitric oxide synthase inhibition on proteinuria in glomerular immune injury. 1663 6