Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.1.17 (
ornithine decarboxylase
)
6,351
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
High doses of folate and its
quinazoline
analogue with antitumour activity, N10-propargyl-5,8-dideazafolic acid (CB 3717), caused severe renal damage in mice, leading in the case of folate to death. The mouse kidneys increased in weight, which was accompanied by time- and dose-dependent induction of
ornithine decarboxylase
(
ODC
) activity. In contrast, methotrexate (MTX) had negligible effect on mouse kidneys except when applied together with the non-steroidal antiinflammatory drug, indomethacin.
...
PMID:Ornithine decarboxylase induction in mouse kidney as indicator of renal damage. Differential nephrotoxic effect of anticancer antifolate drugs. 191 20
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.
...
PMID:Catecholamines participate in the induction of ornithine decarboxylase gene expression in normal and hyperplastic mouse kidney. 1035 16
