RAT ANTIZYME INHIBITS THE ACTIVITY BUT DOES NOT PROMOTE THE DEGRADATION OF MOUSE ORNITHINE DECARBOXYLASE IN TRYPANOSOMA-BRUCEI

Ornithine decarboxylase (ODC) of African kypanosomes is an important t arget for anti-trypanosomal chemotherapy because of its remarkable sta bility in vivo, The in vivo activity and stability of mammalian ODC ar e regulated by polyamines, Polyamines induce antizyme, which inactivat es ODC by tight association and promotes degradation of ODC by the mam malian 26 S proteasome, Here we found, in contrast to mammalian cells, that polyamines caused no reduction of ODC activity in Trypanosoma br ucei, Mouse ODC expressed in T. brucei was also unaffected by exogenou s polyamines, suggesting that a mammalian antizyme equivalent may be a bsent in T. brucei, The rat antizyme expressed in T. brucei was found capable of inhibiting mouse ODC activity by the formation of rat antiz yme-mouse ODC complex, However, complex formation did not lead to degr adation of mouse ODC in T. brucei, Further in vitro experiments sugges ted the presence of an inhibitory factor(s) in trypanosome, which inte rferes with the degradation of mouse ODC, We also demonstrated the pre sence of proteasomes in T. brucei, But the mobility of the trypanosoma l proteasome on native gel is different from that of the mammalian pro teasome, Thus, the absence of antizyme, the presence of inhibitory fac tor(s), and the differences between trypanosomal and mammalian proteas ome may account for the stability of mouse ODC in T. brucei cells,