Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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The nephropathy induced by mercuric chloride was assessed in unilaterally nephrectomized (NPX) and sham-operated (SO) rats using histological and urinalysis techniques. This assessment was carried out in order to test whether or not rats are more susceptible to the nephrotoxic effects of mercuric chloride after unilateral nephrectomy and a period allowing for compensatory renal growth. Twelve days after surgery both NPX and SO rats were given a single 1.5, 2.0 or 2.5 mumol/kg dose of mercuric chloride (i.v.). Twenty-four hours after the 1.5 or 2.0 mumol/kg dose of mercuric chloride was administered, cellular and tubular necrosis in the pars recta segments of proximal tubules in the outer medulla was more severe in NPX rats than in SO rats. Moreover, the urinary excretion of a number of cellular enzymes (e.g. lactate dehydrogenase) and plasma solutes (e.g. albumin) was greater in NPX rats than in SO rats. At the 2.5 mumol/kg dose of mercuric chloride, renal tubular damage was quite extensive in both groups of rats; to such an extent that possible differences in renal tubular damage between the NPX and SO rats could not be determined histologically. However, the urinary excretion of alanine aminopeptidase was greater in the NPX rats than in the SO rats. Therefore, based on the aforementioned findings, rats that have undergone and adapted to a reduction in renal mass (i.e. unilateral nephrectomy) appear to be more vulnerable to the nephrotoxic effects of mercuric chloride than rats with two normal kidneys.
Virchows Arch B Cell Pathol Incl Mol Pathol 1987
PMID:Mercuric chloride-induced nephrotoxicity in the rat following unilateral nephrectomy and compensatory renal growth. 289 Dec 17

Rats immunized with an emulsion of Engelbreth-Holm-Swarm (EHS) tumour and Freund's complete adjuvant (FCA) excreted large amounts of urinary protein from the 14th week after the initial immunization. The amount of urinary protein increased progressively and, after 1 year, reached over 1 g/day. Kidneys removed from immunized rats at 10 weeks, 24 weeks and 1 year after the initial immunization were examined by immunofluorescence, light and electron microscopy. By immunofluorescence microscopy, granular deposits of rat immunoglobulins (Igs) were observed along the glomerular capillary walls from the 10th week until the end of the observation period. Glomerular membranous transformation was observed from the 24th week by light microscopy. The glomerular capillary walls were thickened and argyrophilic spikes and vacuolations were detected. At 1 year the severity of these changes was increased. Electron microscopic examination showed only a few electron-dense deposits after 10 weeks, but after 24 weeks numerous electron-dense deposits were detected in all glomeruli, the glomerular basement membrane was thickened and irregular and podocyte foot processes were effaced. At 1 year, dense deposits were located intramembranously and their density decreased from the circumference to the centre. Lesions characteristic of human membranous nephritis were observed in this model, the appearances at 10 weeks, 24 weeks and 1 year corresponding to stages I, II and III, respectively, of the classification of Ehrenreich and Churg (1968). Comparison of the immunohistochemical abnormalities in this model and in Heymann nephritis revealed antigenic cross-reactivity; there appears to be common antigenicity between the immune deposits in the glomeruli in both models, cell surface antigens in the EHS tumour and those located in the cell surface antigens in the brush borders of proximal convoluted tubules. Although the antigens responsible have not yet been clearly identified, in this paper I describe a new model of membranous nephritis, tentatively termed EHS nephropathy.
Virchows Arch B Cell Pathol Incl Mol Pathol 1988
PMID:EHS nephropathy. A long-term morphological and immunohistochemical study. 290 87

The histopathology of the acute and chronic kidney reaction to low-frequency nonionizing electromagnetic radiation was evaluated in New Zealand white rabbits treated with multiple exposure to 27.12-MHz radiofrequencies. At the end of treatment, the animals exhibited focal tubular necrosis and focal and segmental glomerular sclerosis which in a few months evolved into a membranous nephropathy. The latter was characterized by a diffuse, granular localization of rabbit gamma-globulin and complement in most glomeruli and by electron-dense deposits in the subepithelial zone of the glomerular capillary walls, suggesting that these glomerular changes are induced by the localization of antigen-antibody complexes. The data obtained provide strong evidence for the potential nephrotoxicity of radiofrequency radiation and indicate that these nonionizing types of radiation may be capable of eliciting autoimmune phenomena that are likely responsible for the evolution of renal disease in rabbits.
Exp Mol Pathol 1988 Aug
PMID:Effects of radiofrequency radiation on rabbit kidney: a morphological and immunological study. 339 66

Studies were conducted to assess the renal functional state in two recently discovered diabetic chimpanzees. Both were nonobese, adult female animals with the non-insulin-dependent form of impaired glucose tolerance, analogous to the Type II or nonobese, maturity-onset diabetes of humans. Both animals displayed moderate-to-heavy proteinuria and glycosuria in response to intravenous administration of glucose or tolbutamide. Chimpanzee number 333, but not number 1037, had fasting proteinuria and chronic hypertension. Renal function studies, using the inulin clearance method, demonstrated significantly decreased glomerular filtration rates and elevated rates of sodium excretion for both animals. The rate of chloride excretion was also elevated in animal number 1037, but potassium excretion was apparently unaffected in both animals. Abnormal serum biochemical parameters demonstrated for chimpanzee number 333 included elevations in calcium, magnesium, creatinine, urea nitrogen, and uric acid; animal number 1037 had only an elevated serum creatinine. Results are consistent with the occurrence of renal disease similar to the nephropathy that develops in human diabetics. The difference in severity of renal impairment in the two chimpanzees is possibly related to differences in duration and severity of impaired glucose tolerance. A progression of both diabetic and renal disorders is most probable.
Exp Mol Pathol 1983 Apr
PMID:Impaired renal function in diabetic chimpanzees (Pan troglodytes). 683 45

A strain of rats bred at the Nuclear Study Center of Mol (C.E.N.) develops a nephropathy characterized by granular deposition of immunoglobulin and complement in the renal glomeruli and tubules. We have attempted to specify the complement activation pathways (classical or alternate) in this disease by looking for their initial components (C1q, C3 and C4) in tissue lesions. The immunohistologic and histologic course of the disease has been followed in male and female rats. Immunohistologic results show that glomerular and tubular injury in CEN Wistar rats may be mediated by the classical pathway of complement activation. Histologic data demonstrate that the tubular, glomerular, and interstitial lesions appear in both sexes, but are more extensive and develop earlier in male rats. The lipopigments found in tubular cells suggest a lysosomal dysfunction which might contribute to the progress of the disease.
 ...
PMID:Spontaneous immunoglomerulonephritis in Wistar rats. 743 38

Nephropathy, one of the major complications of diabetes mellitus, is characterized by an early increase in kidney size. In experimental models of diabetes, this event is preceded by a rapid and transient rise in kidney IGF-I levels, at least in adult animals. Since diabetes-associated renal changes are uncommon in young patients, we investigated the early changes in the components of the IGF system following induction of diabetes in prepubertal and postpubertal rats. The rationale for this study was the evaluation of potential differences which could lead to kidney complications only at adult stages. Unlike the situation in the postpubertal kidney, in which there was a transient accumulation of extractable IGF-I 24-48 h after streptozotocin (STZ) administration, there was a decrease of approximately 12-fold in the level of IGF-I in the prepubertal kidney over the same period of time. Paradoxically, kidney IGF-I mRNA levels were reduced by approximately 50% in the postpubertal rat 24 h after STZ treatment, whereas in the prepubertal kidney IGF-I mRNA levels were unaltered. Furthermore, the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding to kidney membranes of postpubertal diabetic rats were similar to the levels in control kidneys. On the other hand, both the levels of IGF-I receptor mRNA and 125I-labelled IGF-I binding were increased (approximately 2.5-fold (after 24 h) and approximately 3-fold (after 48 h) respectively) in prepubertal animals. In addition, increased expression of IGF-binding protein (IGFBP)-1 mRNA was seen early in diabetes in both pre- and postpubertal rats. The results of this study suggest that the transient accumulation of IGF-I in the kidney of the postpubertal diabetic rat may not be due to an increase in the local synthesis of IGF-I, but rather to an increase in IGF-I uptake from the circulation due to non-membrane-associated IGFBP-1. The lack of accumulation of IGF-I in the prepubertal kidney probably reflects the approximately 10-fold lower levels of circulating IGF-I in young as compared with adult diabetic rats.
J Mol Endocrinol 1994 Apr
PMID:Differential accumulation of insulin-like growth factor-I in kidneys of pre- and postpubertal streptozotocin-diabetic rats. 752 Feb 45

Diffuse oesophageal leiomyomatosis (DL), an inherited smooth muscle proliferation process, has been reported to be associated with Alport syndrome (AS), a familial nephropathy, mainly dominant X-linked inherited, and characterized by ultrastructural changes of the glomerular basement membrane. The COL4A5 gene, encoding the alpha 5 chain of type IV collagen, has been identified as the site of mutations in families with X-linked AS. Recently, a novel alpha 6(IV) collagen chain encoding gene has been mapped closely upstream of COL4A5, and disruption of the 5' end of both genes has been reported in four patients with DL and AS (DL-AS). Here, we report a long-range restriction map around the COL4A6 locus, and show that the COL4A5/COL4A6 deletion observed in seven patients with DL-AS encompasses only the two first exons of COL4A6, with a breakpoint located in the second intron of COL4A6, whose size exceeds 65 kb. Furthermore, we demonstrate that three patients with AS without DL, known to have a deletion of the 5' part of the COL4A5 gene, display a larger deletion in COL4A6. Moreover, a COL4A6 mRNA product was detected by reverse-transcription-polymerase chain reaction in an oesophageal tumour sample of a patient with DL-AS. These results suggest that DL-AS could be caused by an abnormal truncated alpha 6(IV) chain.
Hum Mol Genet 1995 Jan
PMID:Deletions of both alpha 5(IV) and alpha 6(IV) collagen genes in Alport syndrome and in Alport syndrome associated with smooth muscle tumours. 771 41

Ca2+ transport in kidney has gained considerable attention in the recent past. Our laboratory has been involved in understanding the regulatory mechanisms underlying Ca2+ transport in the kidney across the renal basolateral membrane. We have shown that ANP, a cardiac hormone, mediates its biological functions by acting on its receptors in the kidney basolateral membrane. Furthermore, it has been established that ANP receptors are coupled with Ca2+ ATPase, the enzyme that participates in the vectorial translocation of Ca2+ from the tubular lumen to the plasma. It is possible that a defect in the ANP-receptor-effector system in diabetes (under certain conditions such as hypertension) may be associated with abnormal Ca2+ homeostasis and the development of nephropathy. Accordingly, future studies are needed to establish this hypothesis.
Mol Cell Biochem 1994 Jun 15
PMID:Renal handling of Ca2+ in diabetes. 781 51

Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.
Res Commun Mol Pathol Pharmacol 1994 Nov
PMID:Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy. 788 71

We have sequenced and studied the expressed protein of an HPRT mutation characterized by 5-12% residual erythrocyte activity, for which affected males exhibit hyperuricemia, arthritis and renal disease but are without severe neurological involvement. The HPRTMoose Jaw mutation is due to a single C to G transversion at nucleotide 582 relative to initiation of translation corresponding to substitution of aspartate 194 by glutamate. The mutant and wild type proteins were expressed and purified using the bacterial expression vector, pMAL-c2. The Km for hypoxanthine was increased 12-fold from 0.94 +/- 0.26 to 11.5 +/- 1.3 microM for control and mutant respectively. The apparent Km for PP-ribose-P was increased 44-fold from 6.8 +/- 0.6 to 295 +/- 7 microM for control and mutant respectively. Although the kcat of the mutant protein was equivalent to wild type, the catalytic efficiency, kcat/Km, of the purified mutant protein was only 6 and 3% of wild type with hypoxanthine and PP-ribose-P respectively. The mutant protein also exhibited positive cooperativity with PP-ribose-P, having a Hill coefficient of 2.3. The decreased substrate affinities and PP-ribose-P associated cooperativity of HPRTMoose Jaw provide additional evidence for the influence of carboxy-terminal residues of HPRT in specific catalytic functions.
Hum Mol Genet 1994 Aug
PMID:Sequence, expression and characterization of HPRTMoose Jaw: a point mutation resulting in cooperativity and decreased substrate affinities. 798 18


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