Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P67775 (alpha isoform)
 797 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is evidence that mediators of inflammation including components of the cytokine system are present in human and experimental diabetic kidney disease. CCAAT/enhancer-binding proteins (C/EBPs) represent a family of cytokine-inducible transcription factors. C/EBPs themselves regulate cytokine expression and also the expression of acute-phase reactants and connective tissue proteins. At least three C/EBP isoforms (alpha, beta, delta) are known. Upon stimulation with cytokines or bacterial lipopolysaccharide, the expression of the alpha isoform typically decreases, and the expression of the beta and/or delta isoforms increases. In view of the fact that components of the inflammatory response are present in diabetic kidney disease, there is a potential that the expression and activity of renal C/EBPs are altered in the diabetic state. In this study we sought to examine the status of C/EBP proteins in kidneys of rats with streptozotocin-induced diabetes mellitus. Diabetes was induced in 5 male Sprague-Dawley rats. Eight weight-matched non-diabetic rats were used as controls. Animals were sacrificed after 4 weeks, and the whole kidney nuclear protein was extracted. An electrophoretic mobility shift assay showed that DNA-binding activity was present in all five kidney nuclear extracts of the diabetic animals, but in only 2 out of 8 control samples (p < 0.05). A supershift assay showed that the DNA-bound protein complex consisted mainly of the C/EBPbeta isoform. Western analysis showed an increase of the C/EBPbeta protein in renal nuclear extracts of the diabetic animals compared to controls (p < 0.05). There was a decrease of the C/EBPalpha protein in the kidney nuclear extracts of the diabetic animals compared to controls (p < 0.05). We conclude that renal C/EBP dynamics are altered in experimental diabetes mellitus and that the patterns of C/EBP changes resemble those observed after cytokine or lipopolysaccharide stimulation.
Nephron 1998
PMID:Renal CCAAT/enhancer-binding proteins in experimental diabetes mellitus. 967 32

In patients with renal diseases, proteinuria is a major determinant of progressive renal failure, probably by causing tubular cell injury. Little is known on extent and site of tubular cell injury in patients with proteinuria. Glutathione S transferases (GST) are cytosolic enzymes. The alpha isoform is present only in proximal tubular cells, whereas the pi isoform is confined to distal tubular cells. We have studied the urinary excretion of both isoenzymes in 56 (38 male and 18 female) patients with glomerular diseases and proteinuria. The mean age was 45 +/- (SD) 16 years, the median creatinine clearance was 80 (range 27-159) ml/min, and the median albuminuria was 4.2 (range 0.7-16.9) g/10 mmol creatinine. The excretions of both GST alpha (median 35.9 ng/10 mmol creatinine) and GST pi (median 24.8 ng/10 mmol creatinine) were elevated as compared with control values (upper limits 10 and 12 ng/10 mmol creatinine, respectively). The urinary excretion of GST pi, but not that of GST alpha, was inversely correlated with the creatinine clearance. The highest levels of GST alpha were found in patients with a well-preserved renal function, whereas highest levels of GST pi were found in patients with renal failure. In a small number of patients we performed immunofluorescent studies of renal tissue. An increased urinary excretion of GST alpha correlated with brush border damage and decreased staining of proximal tubules for that isoenzyme. Our data suggest that in patients with proteinuria initial injury is apparent at the proximal tubules. Measurements of GST alpha and GST pi appear useful to study longitudinal timing and site of proteinuria-induced tubular cell injury.
Nephron 2000 Jun
PMID:Urinary excretion of glutathione S transferases alpha and pi in patients with proteinuria: reflection of the site of tubular injury. 1086 17