Induction of apoptosis and CD10/neutral endopeptidase expression by jaspamide in HL-60 line cells
Induction of apoptosis and CD10/neutral endopeptidase expression by jaspamide in HL-60 line cells
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DOI：
10.1007/s00018-002-8515-6
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发表时间：
2002-08-01
影响因子：
8
通讯作者：
Kitano, K
中科院分区：
文献类型：
--
作者：
Cioca, DP;Kitano, K
茉莉酰胺(Jasplakinolide)是从茉莉属海绵中分离得到的一种天然多肽，具有杀菌和抑制生长的活性。我们研究了茉莉酸激肽内酯通过程序性死亡诱导HL-60人早幼粒白血病细胞系活力丧失的过程，发现这一过程伴随着凋亡细胞表面中性内切酶(NEP)/CD10的表达。HL-60细胞表面或胞浆内通常不表达可检测到的NEP/CD10，但茉莉胺处理后，CD10从头合成，其表达可被放线菌酮抑制。一旦合成，NEP/CD10就会干扰传递给HL-60细胞的茉莉酸激肽内酯信号。用NEP抑制剂磷酰胺或抗CD10单抗抑制NEP/CD10可显著增加细胞凋亡诱导。单核/巨噬细胞分化试剂维生素D-3和佛波酯13-醋酸酯预先孵育细胞可阻断CD10在细胞表面的出现，但粒细胞分化试剂维甲酸或二甲基亚砜不能阻断CD10的出现。此外，在原单核细胞系U937和成熟单核细胞系THP-1中，茉莉酰胺诱导细胞凋亡，但不诱导CD10表达。在HL-60细胞中，CD10的表达被广谱半胱氨酸天冬氨酸氨基转移酶抑制剂benzyioxacarbonyl-Val-Ala-Asp-fluoromethylketone，部分但不是完全阻断，这表明诱导细胞凋亡与CD10的合成有关。提示CD10的表达与茉莉胺诱导HL-60细胞程序性死亡有关，也与HL-60细胞的粒细胞分化有关。
Jaspamide (jasplakinolide) is a natural peptide isolated from marine sponges of Jaspis species and has fungicidal and growth-inhibiting activities. We characterized the jasplakinolide-induced loss of viability by programmed cell death in the HL-60 human promyelocytic leukemia cell line and found that this process was accompanied by neutral endopeptidase (NEP)/CD10 expression on the surface of the apoptotic cells. HL-60 cells do not normally express detectable amounts of NEP/CD10 on their surface or intracytoplasmically, but upon jaspamide treatment, CD10 was synthesized de novo, its expression being inhibited by cycloheximide pretreatment. Once synthesized, NEP/CD10 interfered with the jasplakinolide signal delivered to HL-60 cells. Inhibition of NEP/CD10 by the NEP inhibitor phosphoramidon or by an anti-CD10 monoclonal antibody significantly increased apoptosis induction. The appearance of CD10 on the cell surface was blocked by preincubation of the cells with the monocytic/macrophage-differentiating agents vitamin D-3 and phorbol 12-myristate 13-acetate, but not by the granulocytic differentiating agents retinoic acid or dimethyl sulfoxide. Moreover, in the promono-cytic U937 and mature monocytic THP-1 cell lines, jaspamide induced apoptosis but not CD10 expression. In HL-60 cells, CD10 expression was partially but not totally blocked by the broad-spectrum caspase inhibitor benzyioxacarbonyl-Val-Ala-Asp-fluoromethylketone, indicating a connection between apoptosis induction and CD10 synthesis. Our findings suggest that the CD10 expression is related to the programmed cell death induction by jaspamide, and also with the process of granulocytic differentiation in HL-60 cells.