Modulatory effect of dexamethasone on ornithine decarboxylase activity and gene expression: a possible post-transcriptional regulation by a neutral metalloprotease.
The intracellular effect of dexamethasone (DXME) on the activity and gene expression of ornithine decarboxylase (ODC) was studied in Syrian hamster embryo cells (SHE). The ODC activity (expressed as nmoles decarboxylated ornithine mg-1 protein h-1) was 4.61 +/- 0.14 in untreated cells, whereas it increased to 14.38 +/- 0.26 after 5 h treatment with 1.6 x 10(-7) M TPA. In contrast, DXME (2.5 x 10(-5) M) reduced the ODC activity by 50 per cent to 2.35 +/- 0.22. In cells co-treated for 5 h with TPA and DXME, ODC activity decreased to the level of the untreated cells. However, when DXME was added 3 h after TPA treatment for 2 h, in the continuous presence of TPA, the ODC activity unexpectedly increased further to 16.44 +/- 1.05. The modulation of ODC activity correlated partly with the level of ODC mRNA. Thus when cells were treated with TPA, the ODC mRNA increased threefold, whereas it decreased by 30 per cent when the cells were exposed to DXME. In TPA-DXME co-treated cells, as in TPA pretreated cells followed by DXME for 2 h, a decrease (31.25 per cent and 12.5 per cent respectively) was observed in ODC mRNA. In turnover studies, DXME was found to increase the stability of ODC; the discrepancy between ODC activity and ODC mRNA levels could result from an inhibitory effect of the corticoid on proteolysis of ODC. Studies of lysosomal protease showed that the activities of cathepsins L, B and H decreased following TPA treatment. DXME also inhibited cathepsin L and B activities, but stimulated cathepsin H.(ABSTRACT TRUNCATED AT 250 WORDS)
Nguyen-Ba
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G
Laboratory of Cellular Pharmacology, ICIG, Villejuif, France.
Robert
S
S
Dhalluin
S
S
Tapiero
H
H
Hornebeck
W
W
D000818:Animals; D002403:Cathepsins / Q000032:analysis; D002478:Cells, Cultured; D006224:Cricetinae; D003907:Dexamethasone / Q000494:pharmacology*; D004622:Embryo, Mammalian / Q000166:cytology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008247:Lysosomes / Q000201:enzymology; D008647:Mesocricetus; D008666:Metalloendopeptidases; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D012323:RNA Processing, Post-Transcriptional; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D003907:Dexamethasone; D002403:Cathepsins; D008666:Metalloendopeptidases; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate