鸟氨酸脱羧酶特性的改变导致布氏罗得西亚锥虫对D，L-α-二氟甲基鸟氨酸产生耐受性。
Alterations in ornithine decarboxylase characteristics account for tolerance of Trypanosoma brucei rhodesiense to D,L-alpha-difluoromethylornithine.
作者信息
Iten M, Mett H, Evans A, Enyaru J C, Brun R, Kaminsky R
机构信息
Swiss Tropical Institute, Basel.
出版信息
Antimicrob Agents Chemother. 1997 Sep;41(9):1922-5. doi: 10.1128/AAC.41.9.1922.
Abstract
Ornithine decarboxylase (ODC), the target enzyme of D,L-alpha-difluoromethylornithine (DFMO), was investigated in four DFMO-tolerant Trypanosoma brucei rhodesiense isolates from East Africa and two DFMO-susceptible T. b. gambiense isolates from West Africa. Neither drug uptake nor inhibition of ODC activity by DFMO in cellular extracts differed in the two trypanosome subspecies. However, the specific ODC activity of the cellular extracts was three times as high in T. b. rhodesiense isolates as in T. b. gambiense isolates. Furthermore, a significant difference in the turnover rate of ODC was observed. The time required to induce a 50% reduction of T. b. rhodesiense ODC activity under cycloheximide pressure (tentative half-life) was about 4.3 h, whereas that required for T. b. gambiense ODC was longer than 18 h. We concluded that the higher specific ODC activity and faster enzyme turnover contributed to a substantial degree to the DFMO tolerance observed in the East African T. b. rhodesiense isolates.
摘要
鸟氨酸脱羧酶（ODC）是D，L-α-二氟甲基鸟氨酸（DFMO）的靶酶，在来自东非的4株耐DFMO的布氏罗得西亚锥虫分离株和来自西非的2株对DFMO敏感的布氏冈比亚锥虫分离株中进行了研究。在这两种锥虫亚种中，细胞提取物对DFMO的药物摄取和ODC活性抑制均无差异。然而，细胞提取物的特异性ODC活性在布氏罗得西亚锥虫分离株中是布氏冈比亚锥虫分离株中的三倍。此外，还观察到ODC周转率存在显著差异。在环己酰亚胺压力下诱导布氏罗得西亚锥虫ODC活性降低50%所需的时间（暂定半衰期）约为4.3小时，而布氏冈比亚锥虫ODC所需时间超过18小时。我们得出结论，较高的特异性ODC活性和更快的酶周转率在很大程度上导致了在东非布氏罗得西亚锥虫分离株中观察到的对DFMO的耐受性。
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