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)

Cysteinyl leukotrienes (LT) play an important role in the development of experimental glomerulonephritis (GN). We have partially purified and characterized LTC4 synthase, the enzyme responsible for cysteinyl LT formation, from rat renal microsomes and have investigated this enzyme activity in nephritic rats. LTC4 formation, measured in vitro, was linear for > 10 min at 25 degrees C in the presence of 50 mM serine borate (an inhibitor of gamma-glutamyl transpeptidase), with Km values for LTA4 and GSH of 56 microM and 8.5 mM, respectively. Detergent solubilization and anion-exchange chromatography of microsomal proteins resulted in a 7-fold increase in enzyme specific activity. Enzymatic and immunoblot analysis demonstrated that cytosolic and microsomal glutathione S-transferase (GST) activities were distinct from LTC4 synthase activity. Comparison of LTC4 synthase activity in nephritic rats over 21 days revealed an initial increase over the first 24 h following injection of nephrotoxic sera, followed by a subsequent decline until day 7 and a gradual recovery by day 21. Inhibition of LT biosynthesis with MK-0591 (10 mg kg-1 d-1) reduced GN-associated proteinuria by 72% (P < 0.05). These results suggest a potential mechanism for enhanced cysteinyl LT formation in the development of experimental GN and further support their causal role in the etiology of this disease.
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PMID:Renal leukotriene C4 synthase: characterization, partial purification and alterations in experimental glomerulonephritis. 782 26

We assessed the role of leukotrienes (LTs) in Munich-Wistar rats with passive Heymann nephritis (PHN), an animal model of human membranous nephropathy. 10 d after injection of anti-Fx1A antibody, urinary protein excretion rate (Upr) in PHN was significantly higher than that of control. Micropuncture studies demonstrated reduced single nephron plasma flow and glomerular filtration rates, increased transcapillary hydraulic pressure difference, pre- and postglomerular resistances, and decreased ultrafiltration coefficient in PHN rats. Glomerular LTB4 generation from PHN rats was increased. Administration of the 5-LO activating protein inhibitor MK886 for 10 d markedly blunted proteinuria and normalized glomerular hemodynamic abnormalities in PHN rats. An LTD4 receptor antagonist SK&F 104353 led to an immediate reduction in Upr and to reversal of glomerular hemodynamic impairment. Ia(+) cells/glomerulus were increased in PHN rats. In x-irradiated PHN rats, which developed glomerular macrophage depletion, augmented glomerular LT synthesis was abolished. Thus, in the autologous phase of PHN, LTD4 mediates glomerular hemodynamic abnormalities and a hemodynamic component of the accompanying proteinuria. The synthesis of LTD4 likely occurs directly from macrophages or from macrophage-derived LTA4, through LTC4 synthase in glomerular cells.
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PMID:Leukotriene D4 is a mediator of proteinuria and glomerular hemodynamic abnormalities in passive Heymann nephritis. 838 88