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)

To search for new urinary protein biomarkers of cadmium toxicity, we used quantitative two-dimensional electrophoresis (2DE) and analysed urine samples from 18 male cadmium recovery plant employees whose mean age was 47 +/- 15.6 years (+/- 1 SD) and whose urine cadmium levels ranged from 0.14 microgram l-1 to 20.4 micrograms l-1 (0.06-37.1 micrograms g-1 creatinine). Image analysis of the silver-stained gels yielded intensity (concentration) values for a mean number, per person, of 825 +/- 184 urinary proteins (spots) and found 596 +/- 218 matched proteins (the same proteins in two or more gels) per person. Total urinary protein and the sum of all spot intensities were positively correlated (P = 0.0447 and P = 0.0616, respectively) with urinary cadmium (UCD), as measured by atomic absorption spectroscopy. The combined sum of the intensities of all acidic proteins with a relative molecular weight (M(r)) below 40 kDa was correlated with UCD (P = 0.0461), revealing a low M(r), acidic proteinuria as UCD increased. Multiple hypothesis testing by regression analysis of the intensities of matched proteins with UCD revealed 14 unidentified proteins that were considered candidates for biomarkers of cadmium exposure. The best two candidate proteins--those having M(r)s of less than 13.9 kDa and relative glyceraldehyde-3-phosphate dehydrogenase (G3PDHr) coordinates of -19.7 and -27.2--were excellently resolved in the 2DE gels, and their intensities increased by 323% and 857%, respectively, over the UCD range that was tested. Two other proteins with M(r)s of 23.9 kDa and 29.2 kDa and with acidic net charges were not as well resolved. Six very acidic proteins, with M(r)s ranging from 88.8 to 90.7 kDa and with intensities highly correlated with UCD, appeared to be related and were resolved as a 'charge train' (a group of related proteins, or isoforms, differing only by small changes in net charge). Four proteins appeared to increase only when the UCD concentration was above a threshold of 16 micrograms l-1.
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PMID:Quantitative two-dimensional electrophoretic detection of possible urinary protein biomarkers of occupational exposure to cadmium. 851 44

Lecithin-cholesterol acetyltransferase (LCAT) is involved in the synthesis of plasma cholesteryl esters and is pivotal in the maturation of plasma high-density lipoprotein (HDL) and conversion of HDL3 to HDL2. In nephrotic syndrome (NS), the ratio of HDL2 to HDL3 is low even though the total concentration of HDL is generally normal. We hypothesize that the reduced HDL2/HDL3 ratio in NS is due to urinary losses of LCAT, leading to plasma LCAT deficiency. To test this hypothesis, Sprague-Dawley rats were randomized to NS (given 130 mg puromycin aminonucleoside on day 1 and 60 mg ip on day 14) or control groups and were studied on day 30. To dissect the effect of proteinuria from hypoalbuminemia, a group of Nagase rats with inherited hypoalbuminemia was included. Hepatic LCAT and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA abundance and plasma and urine LCAT activity were measured. The NS group showed a fourfold rise in serum cholesterol and triglycerides, a fivefold rise in free cholesterol, and a fourfold fall in the HDL-to-total cholesterol ratio. Despite severe hypoalbuminemia, the Nagase rats showed only a mild elevation of serum cholesterol and triglycerides with a normal serum free cholesterol and HDL-to-total cholesterol ratio. The NS group exhibited a normal hepatic LCAT-to-GAPDH mRNA ratio, a marked reduction in plasma LCAT activity, and a significant increase in urinary LCAT excretion. LCAT/GAPDH mRNA and plasma and urine LCAT were normal in Nagase rats. Thus NS led to heavy urinary losses and reduced plasma concentration of LCAT, despite normal hepatic LCAT mRNA abundance. However, hypoalbuminemia, per se, without proteinuria as seen in the Nagase rats had no effect on plasma LCAT or the HDL-to-total cholesterol ratio. Therefore, proteinuria, not hypoalbuminemia, causes LCAT deficiency and a depressed HDL-to-total cholesterol ratio in NS.
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PMID:Acquired lecithin-cholesterol acyltransferase deficiency in nephrotic syndrome. 1129 24