Ornithine decarboxylase induction and polyamine biosynthesis by phorone (diisopropylidene acetone), a glutathione depletor, in rats.
The administration of Phorone (diisopropylidene acetone, 250 mg/kg, ip.), a glutathione (GSH) depletor, markedly induced (400-fold of the control at 12 hr) ornithine decarboxylase (ODC) in the liver of rats. Parallel to ODC induction there was a marked increase in hepatic putrescine content. Phorone also produced an increase in spermidine content and a decrease in spermine content. The effects of phorone on ODC and putrescine content occurred dose-dependently with more than a 1000-fold increase in ODC activity over the controls at a dose of 500 mg/kg. Pretreatment of rats with buthionine sulfoximine, a GSH depletor by inhibition of biosynthesis, failed to inhibit phorone-mediated induction of ODC. In contrast, pretreatment with GSH, but not post-treatment, blocked the induction of ODC by phorone.
Oguro
T
T
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
Numazawa
S
S
Yoshida
T
T
Kuroiwa
Y
Y
D000818:Animals; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism*; D007659:Ketones / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011073:Polyamines / Q000096:biosynthesis*; D011700:Putrescine / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012997:Solvents; D013095:Spermidine / Q000096:biosynthesis; D013096:Spermine / Q000096:biosynthesis
D007659:Ketones; D011073:Polyamines; D012997:Solvents; D013096:Spermine; C018637:phorone; D009955:Ornithine Decarboxylase; D005978:Glutathione; D013095:Spermidine; D011700:Putrescine