Trypanosoma brucei brucei: regulation of ornithine decarboxylase in procyclic forms and trypomastigotes.
Ornithine decarboxylase (ODC) activity was measured in procyclic forms of Trypanosoma brucei brucei grown in semidefined medium. ODC activity rapidly increased in late log-phase cells which were resuspended in fresh medium. A biphasic induction curve similar to that observed in mammalian cells was observed over an 18-hr period. ODC activity increased 4.5- to 25-fold over control levels measured at zero time. Actinomycin D and cycloheximide inhibited induction by greater than 90%. Polyamines at a level not inhibitory to growth (10 microM) inhibited ODC induction, but only by 30-50%, late in the induction period. Putrescine inhibited the first peak of induction and suppressed activity at 14 hr by 75%. Polyamine analogs such as bis(ethyl)spermidine were not effective suppressors of ODC activity. The half-life of ODC in procyclic forms grown in the presence of cycloheximide was greater than 6 hr, while that of bloodstream trypomastigotes in mice treated with cycloheximide was 5 hr. A single dose of the ODC inhibitor DL-alpha-difluoromethylornithine given to infected rats or mice suppressed trypanosome ODC activity greater than 90% for more than 7 hr. These studies indicate that although trypanosome ODC increases rapidly under log growth conditions, it is less susceptible to fluctuation and external control than the enzyme from mammalian sources. The latter may be a factor in the clinical efficacy of ODC inhibitors.
Bacchi
C J
CJ
Haskins Laboratories, Pace University, New York, New York 10038.
Garofalo
J
J
Santana
A
A
Hannan
J C
JC
Bitonti
A J
AJ
McCann
P P
PP
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D000518:Eflornithine / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006207:Half-Life; D008297:Male; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000378:metabolism; D011700:Putrescine / Q000494:pharmacology; D051381:Rats; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology*
D003609:Dactinomycin; D013096:Spermine; D003513:Cycloheximide; D009955:Ornithine Decarboxylase; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine