Alteration of actin organization by jaspamide inhibits ruffling, but not phagocytosis or oxidative burst, in HL-60 cells and human monocytes
Alteration of actin organization by jaspamide inhibits ruffling, but not phagocytosis or oxidative burst, in HL-60 cells and human monocytes
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DOI：
10.1182/blood.v93.11.3994.411k39_3994_4005
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发表时间：
1999-06-01
期刊：
影响因子：
20.3
通讯作者：
Tsarfaty, I
中科院分区：
文献类型：
--
作者：
Fabian, I;Halperin, D;Tsarfaty, I
Jaspamide是一种天然存在的环状肽，从海绵半astrella minor中分离出来，具有杀真菌和抑制生长的活性。早幼粒细胞HL-60细胞和人单核细胞暴露于jasper酰胺诱导肌动蛋白从典型的纤维网络到局灶聚集体的戏剧性重组。暴露于5 × 10(-8) mol/L或10(-7)mol/L贾斯珀酰胺的HL-60细胞增殖率降低。此外，10(-7)mol/L茉莉酰胺诱导HL-60细胞成熟，55% +/- 5%的细胞出现分叶状细胞核，白血病细胞免疫表型成熟（CD16和CD14 B抗原上调）。进一步的表征表明，f -肌动蛋白在HL-60细胞和暴露于10(-7)mol/L雅斯帕酰胺的人单核细胞中都聚集。此外，在经贾斯丁酰胺处理的HL-60细胞中，观察到总肌动蛋白和可溶性肌动蛋白的新生合成部分均呈剂量依赖性增加。贾斯丁酰胺抑制HL-60细胞和单核细胞的皱缩和细胞内运动，但不影响吞噬活性或呼吸爆发活性。茉莉酰胺诱导的肌动蛋白重组对褶皱的影响，相对于其对吞噬和氧化破裂的可忽略的影响，可能揭示了肌动蛋白参与这些过程的分子机制。甲酰胺破坏正常和恶性哺乳动物细胞的肌动蛋白细胞骨架，对吞噬活性无显著影响，因此可能被认为是一种新的治疗药物。(C) 1999年由美国血液病学会出版。
Jaspamide, a naturally occurring cyclic peptide isolated from the marine sponge Hemiastrella minor, has fungicidal and growth-inhibiting activities. Exposure of promyelocytic HL-60 cells and human monocytes to jaspamide induces a dramatic reorganization of actin from a typical fibrous network to focal aggregates. HL-60 cells exposed to 5 x 10(-8) mol/L or 10(-7) mol/L jaspamide exhibited a reduced proliferation rate. In addition, 10(-7) mol/L jaspamide induced maturation of HL-60 cells as indicated by the appearance of a lobulated nucleus in 55% +/- 5% of the cells and immunophenotypic maturation of the leukemia cells (upregulation of CD16 and CD14 B antigens). Further characterization has shown that F-actin is aggregated both in HL-60 cells and in human monocytes exposed to 10(-7) mol/L jaspamide. Well-spread cultured human monocytes contracted and adopted round shapes after treatment with jaspamide, Moreover, a dose-dependent increase in both total actin and de novo synthesized portions of the soluble actin was observed in jaspamide-treated HL-60 cells. Jaspamide treatment inhibits ruffling and intracellular movement in HL-60 cells and monocytes, but does not affect phagocytic activity or respiratory burst activity. The consequential effects of jaspamide-induced actin reorganization on ruffling, versus its negligible effect on phagocytosis and oxidative burst, may shed light on molecular mechanisms of actin involvement in these processes. Jaspamide disrupts the actin cytoskeleton of normal and malignant mammalian cells with no significant effect on phagocytic activity and may, therefore, be considered as a novel therapeutic agent. (C) 1999 by The American Society of Hematology.