Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.17 (ornithine decarboxylase)
 6,351 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In chronic renal failure (CRF), renal ammoniagenesis and handling of ornithine cycle intermediates (ornithine, citrulline, and arginine) are disturbed. The present study examined the molecular mechanisms of these disturbances in kidney and liver of rats with moderate CRF induced by 5/6 nephrectomy. The steady state level of mRNA for phosphoenolpyruvate carboxykinase (PEPCK) and argininosuccinate synthetase (ASS) in both kidney and liver were unaffected by CRF. On the other hand, that for phosphate-dependent glutaminase (PDG) was increased while that for ornithine decarboxylase (ODC) was decreased in the diseased kidney. Combined with previously reported enzymatic activities, our findings suggest that, in CRF, gene expression is responsible for enzymatic changes of PDG and ODC, not of PEPCK and ASS. Underexpression of ODC, resulting in impaired renal polyamine synthesis, may contribute to progression of CRF. Finally, the significant increase in renal mRNA expression of beta-actin precludes the use of this molecule as a reference in CRF.
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PMID:Effect of chronic renal failure on the abundance of mRNA for enzymes of intermediary metabolism in kidney and liver. 785 37

Altered nitrogen metabolism is a feature of chronic renal failure (CRF). The present study examined changes in renal expression of mRNA for enzymes involved in ornithine and polyamine metabolism, i.e. ornithine aminotransferase (OAT), ornithine decarboxylase (ODC), and S-adenosylmethionine synthetase (S-ADMase), during the early phase of renal insufficiency in rats after 5/6 nephrectomy (Nx). Involvement of androgens, the most potent stimulators of renal ODC, in these changes, was also evaluated inasmuch as testoseronemia is known to be significantly decreased in male uremic subjects. The abundance of mRNA was evaluated by quantitative Northern analysis of total RNA extracted from the remnant kidney of male or female Nx rats. The level mRNA for ODC was depressed by 76, 83, and 79%, that for OAT by 60, 76 and 63%, and that for S-ADMase by 37, 58 and 30%, at, respectively, 2, 7 and 35 days after Nx, in both male and female rats. ODC but not OAT enzyme activity was decreased. The expression of glyceraldehyde-3-phosphate dehydrogenase was only slightly lowered and that of c-myc was unaltered. Renal polyamine content of the remnant kidney was unchanged. It is concluded that in CRF: (1) intrarenal ornithine metabolism and polyamine biosynthesis are greatly impaired; (2) decreased androgens are not involved in these changes; (3) increased ODC is not a prerequisite for kidney hypertrophy; (4) extrarenal polyamines accumulation into the remnant likely compensates for defective renal biosynthesis.
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PMID:Messenger RNA for enzymes of ornithine and polyamine metabolism are selectively underexpressed in kidney of 5/6 nephrectomized rats. 925 82

Gene expression profiling using microarrays (rat-specific array RG-U34A, Affymetrix, U.S.A.) was employed for the investigation of: (1) hormonal regulation of renal function and (2) nephrotoxicity. For this purpose about 8,800 genes were analysed in kidney and, additionally, in liver tissue. Ad 1.) Kidney functions develop during postnatal life. Thus, in vivo transport and accumulation of p-aminohippurate (PAH) was investigated on renal cortical slices (RCS) from 10- and 55-day-old rats. The animals were treated with dexamethasone (DEXA; 60 microg/100 g b.wt./day) for 3 days, which caused a significant reduction in the accumulation of PAH in 10-day-old rats (42 +/- 5% whereas it was only slightly reduced in 55-day-old rats (70 +/- 8%). To further clarify the regulation of renal function by DEXA, results were compared with those obtained previously after in vitro stimulation with DEXA. RCS were incubated for 24 hours in DEXA-containing medium (10(-9) M). Under these conditions DEXA significantly increased the PAH uptake capacity in RCS obtained from 10- and 55-day-old rats up to 126 and 136%, respectively. Thus a stimulation of tubular transport capacity is possible in vitro. The effect of DEXA treatment on the gene expression of the kidney (in vivo) was moderate. Focussing especially on transporters, ion channels, ATPases, glucuronyltransferases, glutathione-S-transferase and cytochrome P450, the expression of only few genes were significantly changed (3 to 50-fold up- or down-regulation). Moreover, distinct age differences were found after in vivo administration of DEXA. The investigation of in vitro effects of DEXA is currently been performed. Ad 2.) The kidney is threatened by nephrotoxins because of its ability to accumulate them. We used a single administration of uranyl nitrate (UN; 0.5 mg/100 g b.wt.) as a model for chronic renal failure (CRF). Clearance experiments were performed 10 weeks after UN administration (maximal symptoms of CRF) in adult female rats. As expected, UN induced interstitial cicatrices with reduced GFR and diminished PAH transport capacity. Despite the impressive morphological and functional changes in the kidney after exposure to UN, the gene expression profiles in the kidneys were only minimally affected: we found significantly changed expression levels for only 20 genes (5 genes were up-regulated [e.g. transgelin], 15 down-regulated [among these the Na-K-Cl-symporter, insulin-like growth factor, kallikrein, and ornithine decarboxylase). The lack of agreement between gene expression data and the nephrotoxic effects of UN can probably be explained by the long time interval between dosing and the assessment of the effect. The results confirm that primary genomic responses are likely to be strongest transiently after exposure and then decrease in intensity.
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PMID:Use of gene chip technology for the characterisation of the regulation of renal transport processes and of nephrotoxicity in rats. 1287 52