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)

Albumin filtered by the glomerulus is reabsorbed in the proximal tubule. We have shown previously that proteinuria stimulates the proximal tubular Na(+)/H(+) exchanger 3 (NHE3) in rats. Activation of NHE3 may be a pathophysiologically important factor in the development of renal salt and water retention observed in the nephrotic syndrome. For examining whether albumin is a specific inducer of proximal tubular Na(+)/H(+) exchange and to determine the molecular mechanisms by which it regulates Na(+)/H(+) exchange, the effect of albumin on NHE3 in opossum kidney cells was studied. Albumin activated Na(+)/H(+) exchange in a time- and dose-dependent manner up to 100% in 48 h. In the early phase of stimulation (2 to 12 h), NHE3 activity was increased without changes in NHE3 protein and mRNA. At 24 h, increased NHE3 activity was accompanied by increase in cell surface NHE3 protein. The increase in surface NHE3 was associated with increased bidirectional trafficking of NHE3 protein between intracellular compartments and the cell surface. At 48 h, total cell NHE3 protein abundance and mRNA were increased as well. Whereas NHE3 translation was increased, NHE3 protein half-life remained unchanged. The effects of albumin on NHE3 protein abundance were modified by hydrocortisone in a complicated pattern. These results indicate that albumin directly regulates proximal tubular NHE3 at multiple levels.
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PMID:Albumin regulates the Na+/H+ exchanger 3 in OKP cells. 1463 28

Human glomerulonephritis (GN) is characterized by sustained proteinuria, sodium retention, hypertension, and edema formation. Increasing quantities of filtered protein enter the renal tubule, where they may alter epithelial transport functions. Exaggerated endocytosis and consequent protein overload may affect proximal tubules, but intrinsic malfunction of distal epithelia has also been reported. A straightforward assignment to a particular tubule segment causing salt retention in GN is still controversial. We hypothesized that 1) trafficking and surface expression of major transporters and channels involved in volume regulation were altered in GN, and 2) proximal tubular endocytosis may influence locally as well as downstream expressed tubular transporters and channels. Effects of anti-glomerular basement membrane GN were studied in controls and megalin-deficient mice with blunted proximal endocytosis. Mice displayed salt retention and elevated systolic blood pressure when proteinuria had reached 10-15 mg/24 h. Surface expression of proximal Na(+)-coupled transporters and water channels was in part [Na(+)-P(i) cotransporter IIa (NaPi-IIa) and aquaporin-1 (AQP1)] increased by megalin deficiency alone, but unchanged (Na(+)/H(+) exchanger 3) or reduced (NaPi-IIa and AQP1) in GN irrespective of the endocytosis defect. In distal epithelia, significant increases in proteolytic cleavage products of alpha-epithelial Na(+) channel (ENaC) and gamma-ENaC were observed, suggesting enhanced tubular sodium reabsorption. The effects of glomerular proteinuria dominated over those of blunted proximal endocytosis in contributing to ENaC cleavage. Our data indicate that ENaC-mediated sodium entry may be the rate-limiting step in proteinuric sodium retention. Enhanced proteolytic cleavage of ENaC points to a novel mechanism of channel activation which may involve the action of filtered plasma proteases.
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PMID:Effects of receptor-mediated endocytosis and tubular protein composition on volume retention in experimental glomerulonephritis. 1919 26