Alterations in ornithine decarboxylase characteristics account for tolerance of Trypanosoma brucei rhodesiense to D,L-alpha-difluoromethylornithine
Alterations in ornithine decarboxylase characteristics account for tolerance of Trypanosoma brucei rhodesiense to D,L-alpha-difluoromethylornithine
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DOI：
10.1128/aac.41.9.1922
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发表时间：
1997-09-01
影响因子：
4.9
通讯作者：
Kaminsky, R
中科院分区：
文献类型：
--
作者：
Iten, M;Mett, H;Kaminsky, R
D，Lα-二氟甲基鸟氨酸的靶标鸟氨酸脱羧酶在4个耐DFMO的布氏锥虫和2个敏感的西非冈比亚锥虫中进行了研究，两个锥虫亚种对药物的摄取和DEMO对ODC活性的抑制都不同。然而，细胞抽提物的比ODC活性在罗得西亚锥虫分离物中是冈比亚锥虫分离物中的三倍。此外，ODC的周转率也有显著差异。在环己酰亚胺压力下(暂定半衰期)，罗德希氏锥虫ODC活性下降50%所需的时间约为4.3h，而冈比亚锥虫ODC所需的时间长于18h。我们得出结论，较高的ODC比活性和较快的酶周转对东非罗德希氏锥虫分离株的DFMO耐受性有很大程度的贡献。
Ornithine decarboxylase (ODC), the target enzyme of D,L-alpha-difluoromethylornithine (DFMO), was investigated in four DFMO-tolerant Trypanosoma brucei rhodesiense isolates from Fast Africa and two DFMO-susceptible T. b. gambiense isolates from West Africa, Neither drug uptake nor inhibition of ODC activity by DEMO 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.