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)

Renal hypertrophy and hyperfiltration are early manifestations of human and experimental diabetes that may contribute to the late development of diabetic nephropathy. The biochemical events resulting in kidney growth in the diabetic state are completely unknown. Since growth of various tissues is accompanied by increased formation of polyamines, we studied whether polyamines were involved in the growth of the kidney observed in diabetic rats. This was done by measuring the activity of the rate-limiting enzyme in the polyamine pathway (ornithine decarboxylase; ODC) in kidneys from control, diabetic and insulin-treated diabetic animals. The ODC activity in the kidney was increased in the diabetic animals with a maximal rise 24 h after diabetes induction (6-fold, P less than 0.01); the activity thereafter declined. However, on day 14 the activity was still significantly elevated (2.5-fold, P less than 0.05). In insulin-treated diabetic animals the kidney ODC activity was only increased 3-fold (P less than 0.05) after 24 h, and for the rest of the study period the activity was about 1.8-fold higher than in control rats. After 14 days the kidneys from diabetic rats were significantly larger than kidneys from both control and insulin-treated diabetic rats, 1066 +/- 43 mg vs. 904 +/- 16 mg and 959 +/- 36 mg, respectively (P less than 0.01). For comparison, the ODC activity was also investigated in muscle. However, in muscle from diabetic animals the ODC activity declined steadily during the 14 days to 34% of control values (P less than 0.01), and insulin treatment completely normalized the ODC activity in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased ornithine decarboxylase activity in kidneys undergoing hypertrophy in experimental diabetes. 151 80

Renal hypertrophy was induced in mice by injection of testosterone. Associated with an increase in renal tissue mass were increases in the concentrations of spermine and spermidine and in the activity of ornithine decarboxylase (ODC), the rate limiting enzyme in their synthesis. The increased activity of ODC was shown to be due to an increase in tissue ODC content. Total tissue actin was not altered by testosterone treatment although the proportion of unpolymerized (soluble) actin was increased significantly. These data are discussed in relation to the postulated mechanism of polyamine stimulation of actin polymerization.
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PMID:Ornithine decarboxylase activity and actin polymerization in testosterone--stimulated mouse kidney. 309 27

The role of ornithine decarboxylase (ODC) and polyamines in kidney hypertrophy is controversial. Since part of this controversy could be related to differences in the model system used by the different authors, we studied the changes in renal ODC and polyamines in six different models of kidney hypertrophy in mice, including compensatory renal hypertrophy produced by unilateral nephrectomy, experimental diabetes, potassium depletion and treatment with hormones such as testosterone, thyroxine and fluorocortisone. Only in the case of renal hypertrophy produced by testosterone administration was there a significant increase in ODC activity and putrescine content in the kidneys. However, the concomitant treatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, as a 2% solution in the drinking water completely abolished the increase of renal ODC, but the kidney weights increased and other androgenic effects, such as the induction of renal beta-glucuronidase, were not affected. Moreover, DFMO-treatment did not prevent the kidney enlargement produced in other types of hypertrophy, even in the cases associated with hyperplasia. The present results support the premise that, at least in mice, the increase in ODC activity and polyamine biosynthesis is not required for kidney growth, and also that in most cases renal enlargement is not accompanied by any increase in the polyamine content.
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PMID:An evaluation of the role of polyamines in different models of kidney hypertrophy in mice. 747 58

Formation of polyamines has previously been shown to play an important role for initial kidney growth in experimental diabetes, as treatment of diabetic rats with a selective ornithine decarboxylase (ODC) inhibitor, initiated immediately after diabetes induction, abolishes the initial kidney growth. In order to investigate the role of polyamine formation for the maintenance of diabetic kidney hypertrophy, ODC inhibition was initiated after manifest kidney hypertrophy had occurred. The kidney weight in diabetic rats was significantly larger than in control rats after a diabetes duration of 7, 14, 50 and 71 days and the total glomerular volume was increased in kidneys from diabetic rats after a diabetes duration of 71 days. Renal activity of ODC was increased in diabetic rats throughout the study period of 71 days. Treatment of diabetic rats with the selective ODC inhibitor di-fluoro-methyl-ornithine (DFMO) was maintained for two periods (days 7-14 and days 50-71). DFMO treatment had no effect on 24-h food consumption, blood glucose concentration or body weight. However, despite almost total inhibition of the kidney ODC activity, there was no effect on kidney growth or total glomerular volume in the DFMO treated diabetic rats compared to placebo treated diabetic rats. Finally, the urinary albumin excretion was markedly increased in diabetic rats with no effects of ODC-inhibition. In conclusion, inhibition of ODC initiated in diabetic rats with manifest kidney enlargement had no effect on renal size, glomerular volume or urinary albumin excretion. These findings together with our previous findings indicate that the role of polyamines in diabetic kidney enlargement is restricted to the first week after diabetes induction.
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PMID:Inhibition of renal ornithine decarboxylase activity fails to reduce kidney size and urinary albumin excretion in diabetic rats with manifest kidney hypertrophy. 779 31

In the testosterone-induced hypertrophic and antifolate (N10-propargyl,5,6-dideazafolic acid, CB 3717)-induced hyperplastic mouse kidney models, a marked increase of two diamine levels--putrescine and cadaverine--occurred which paralleled induced ornithine decarboxylase (ODC) activity. Under these conditions the augmentation of spermidine levels was much smaller, while spermine levels were affected differentially--increased by testosterone and decreased by CB 3717; this resulted in an increase of spermidine/spermine ratio in hyperplastic, but not hypertrophic kidney. alpha-Difluoromethylornithine (DFMO) prevented testosterone- or CB 3717-induced increment of both diamine levels. Spermidine and spermine depletion in response to DFMO was significant in hyperplastic kidney only. DFMO also significantly affected the other biochemical markers of hyperplasia, namely lowered CB 3717-induced cell proliferation rate and increased S-adenosylmethionine decarboxylase (AdoMetDC) activity. In contrast, testosterone-induced hypertrophy was not influenced by DFMO, as judged by the lack of its effect on S-adenosylmethionine synthetase and cystathionine and synthase activity. These results indicate that the increase of putrescine levels does not mediate testosterone-induced renal hypertrophy and possibly also antifolate-induced hyperplasia. The involvement of spermidine in mediation of renal hyperplasia is highly possible, while that of spermine is excluded.
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PMID:Polyamines in testosterone-induced hypertrophic and antifolate-induced hyperplastic mouse kidney. Differential effect of alpha-difluoromethylornithine. 835 43

RU-486 (mifepristone) is a synthetic steroid with potent antiprogesterone and antiglucocorticoid activity, that is currently used as a contraceptive agent. In the present work we have evaluated the antiandrogenic effect of this compound on mouse kidney, a very well known extragenital model of androgen action by studying the effect of RU-486 on renal parameters that depend on androgens, such as renal ornithine decarboxylase (ODC) activity and kidney hypertrophy, as well as the inhibitory action of mifepristone on the induction of renal ODC and kidney hypertrophy elicited by testosterone treatment in female mice and in castrated male. The results showed that: (1) 48 hr after treatment of male mice with of RU-486 (50 mg/kg, four injections) renal ODC activity decreased from 3.381 +/- 490 nmol CO2/h.g to 605 +/- 163 (SD, n = 5); (2) in female mice or orchidectomized male mice, RU-486 also inhibited the renal ODC induction elicited by exogenous administration of testosterone propionate (TP), the magnitude of the inhibition was dependent on the doses of TP and RU-486 used. While RU-486 at a dose of 25 mg/kg inhibited more than 80% ODC induction produced by treatment with 5 mg/kg TP, the same dose did not significantly affect ODC when the dose of TP was increased up to 100 mg/kg. Higher concentration of RU-486 (200 mg/kg) clearly inhibited the increase in ODC produced by treatment with TP 100 mg/kg; (3) RU-486 was more effective in blocking the anabolic effects produced by stanozolol, a steroidal anabolizing agent, than those produced by testosterone; and (4) RU-486 was less effective than the nonsteroidal antiandrogen flutamide in inhibiting renal ODC activity in male mice. Our results clearly indicate that RU-486 possesses moderate antiandrogenic activity in mouse kidney. The possibility that RU-486 may have similar effects in man should be considered when using this drug.
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PMID:Antiandrogenic effect of RU-486 in the mouse kidney. 914 38

Catecholamine depletion, evoked by reserpine, dramatically impaired (5-fold) the testosterone-induced increase of ornithine decarboxylase (ODC) activity in female mouse kidney. However, reserpine did not prevent kidney hypertrophy evoked by testosterone. This is evidenced by the activity of sensitive, biochemical markers of renal hypertrophy, namely arginase and ornithine aminotransferase (OAT), that responded with the increase and decrease of activities to testosterone treatment, respectively. Arginine and ornithine, substrates and/or products of marker enzymes, showed a striking homeostasis as their level was not affected by testosterone and reserpine, and only slightly by DFMO. Northern blot analysis revealed that the ODC mRNA level, that was increased 10-fold by testosterone, was decreased 2-fold in catecholamine-depleted hypertrophic kidney. Thus, ODC transcript level, lowered by reserpine, correlated partially with an attenuated response of ODC activity to testosterone. This was in contrast to DFMO, which inhibited ODC activity, but significantly increased its mRNA content. It is concluded that catecholamines could be involved together with testosterone in regulation of the ODC gene expression in mouse kidney.
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PMID:Catecholamines are required for androgen-induced ODC expression but not for hypertrophy of mouse kidney. 919 72

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

In the quinazoline antifolate (CB 3717)-induced hyperplastic kidney model, a remarkable increase of ornithine decarboxylase (ODC) activity was paralleled by a smaller, but highly significant augmentation of the ODC transcript level. Catecholamine depletion, evoked by reserpine, strongly impaired antifolate-induced ODC expression; the enzyme activity was almost completely abolished while the mRNA level decreased by 60%. Moreover, under conditions of a depleted catecholamine pool, kidney enlargement was significantly reduced confirming our earlier reports on the indispensability of ODC induction for renal hyperplasia (M. Manteuffel-Cymborowska et al. , Biochim. Biophys. Acta, 1182 (1993) 133-141[1]). In normal mouse kidney catecholamines appeared to be inducers of ODC expression. Use of selective agonists of catecholamine receptors demonstrated the importance of dopamine D2 receptors, and to a lower extent beta adrenoreceptors, in the catecholamine mediation of induction of ODC activity and of ODC mRNA levels. These increases were not abolished by an antiandrogen, casodex, suggesting that catecholamine control of ODC expression is an androgen receptor-independent process. The results obtained point to the critical role of renal catecholamines; these biogenic amines are not only involved in the regulation of ODC expression in normal kidney but are also required for the induction of ODC in hyperplastic kidney evoked by antifolate and, as shown recently (M. Manteuffel-Cymborowska et al., Biochim. Biophys. Acta, 1356 (1997) 292-298[2]), in testosterone-induced hypertrophic kidney.
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PMID:Catecholamines participate in the induction of ornithine decarboxylase gene expression in normal and hyperplastic mouse kidney. 1035 16

Polyamines are small biogenic molecules that are essential for cell cycle entry and progression and proliferation. They can also contribute to hypertrophy. The activity of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, increases in the early diabetic kidney to enable renal hypertrophy. Inhibition of ODC in early diabetes attenuates diabetic renal hypertrophy and glomerular hyperfiltration. The current studies examine the temporal profile of renal ODC protein expression and localization, intrarenal polyamine levels, and sites of proliferation in kidneys of rats during the first 7 days of streptozotocin diabetes. ODC mRNA and protein content were increased in diabetic kidneys. High-performance liquid chromatography analysis showed increased intrarenal polyamine concentrations peaking after 24 h of diabetes. A subsequent increase in the number of proliferating proximal tubular cells was detected by in vivo 5-bromodeoxyuridine (BrdU) incorporation on day 3. Surprisingly, immunohistochemical studies revealed that increased ODC protein was apparent only in distal nephrons, whereas the main site of diabetic kidney hypertrophy is the proximal tubule. These findings raise the possibility that polyamines produced in the distal nephron may mediate the early diabetic kidney growth of the proximal tubules via a paracrine mechanism.
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PMID:Increased expression of ornithine decarboxylase in distal tubules of early diabetic rat kidneys: are polyamines paracrine hypertrophic factors? 1271 58


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