Relationship between arachidonate--phospholipid remodeling and apoptosis.
Relationship between arachidonate--phospholipid remodeling and apoptosis.
复制标题
花生四烯酸-磷脂重塑与细胞凋亡的关系。
DOI：
10.1021/bi9530245
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Chilton,FH
中科院分区：
文献类型：
--
作者：
Surette,ME;Winkler,JD;Fonteh,AN;Chilton,FH
我们以前的研究表明，三种结构不同的辅酶A非依赖性转酰酶抑制剂，包括抗增殖的烷基溶血磷脂ET-18-O-CH 3，诱导早幼粒细胞系HL-60的程序性细胞死亡（凋亡）。本研究的目的是更好地阐明负责细胞凋亡的机制。CoA-IT是一种被认为负责哺乳动物细胞的磷脂之间的长链多不饱和脂肪酸如花生四烯酸的重塑的酶。用所有三种CoA-IT抑制剂对HL-60细胞进行长期（24 - 48 h）处理，可抑制标记的花生四烯酸酯从胆碱重塑为含乙醇胺的磷脂分子种类。磷脂中脂肪酸的GC-MS分析显示，CoA-IT抑制剂处理诱导了含花生四烯酸磷脂酰乙醇胺的显著损失和含花生四烯酸磷脂酰胆碱的增加。这种再分配是特定的花生四烯酸，因为质量分布的亚油酸甘油酯不受影响。尽管花生四烯酸的戏剧性的重新分配，总细胞花生四烯酸含量没有改变，也不是总磷脂类的相对分布。磷脂酰胆碱中花生四烯酸的增加特别是由于1-酰基-2-花生四烯酸-sn-甘油-3-磷酸胆碱物质的增加，而PE中花生四烯酸的损失来自1-酰基-和1-烷-1-烯基-2-花生四烯酸-sn-甘油-3-磷酸乙醇胺物质。用外源花生四烯酸或乙醇胺孵育细胞不能逆转CoA-IT抑制剂处理诱导的增殖抑制。与CoA-IT抑制剂孵育还诱导与凋亡相关的特征性细胞质和细胞核变化，如通过透射电子显微镜和DNA片段化所评估的，如通过流式细胞术所确定的。总之，这些数据表明，HL-60细胞中的细胞凋亡，诱导阻断花生四烯酸磷脂重塑，与花生四烯酸在膜磷脂的再分配，并建议，这种改变代表一个信号，控制细胞增殖的能力。
Our previous studies reveal that three structurally distinct inhibitors of the enzyme CoA-independent transacylase, including the antiproliferative alkyllysophospholipid ET-18-O-CH3, induce programmed cell death (apoptosis) in the promyelocytic cell line HL-60. The objective of the current study was to better elucidate the mechanism responsible for apoptosis. CoA-IT is an enzyme believed to be responsible for the remodeling of long chain polyunsaturated fatty acids like arachidonate between the phospholipids of mammalian cells. The chronic (24−48 h) treatment of HL-60 cells with all three CoA-IT inhibitors resulted in the inhibition of the remodeling of labeled arachidonate from choline- into ethanolamine-containing phospholipid molecular species. GC-MS analysis of the fatty acids in phospholipids revealed that CoA-IT inhibitor treatment induced a marked loss of arachidonate-containing phosphatidylethanolamine and an increase in arachidonate-containing phosphatidylcholine. This redistribution was specific to arachidonate since the mass distribution of linoleic acid in glycerolipids was not affected. In spite of the dramatic redistribution of arachidonate, the total cellular arachidonate content was not altered nor was the relative distribution of total phospholipid classes. The increase of arachidonate in phosphatidylcholine was specifically due to an increase in 1-acyl-2-arachidonoyl-sn-glycero-3-phosphocholine species, whereas the loss of arachidonate in PE was from both 1-acyl- and 1-alk-1-enyl-2-arachidonoyl-sn-glycero-3-phosphoethanolamine species. The incubation of cells with exogenous arachidonic acid or ethanolamine did not reverse the inhibition of proliferation induced by CoA-IT inhibitor treatment. Incubation with CoA-IT inhibitors also induced the characteristic cytoplasmic and nuclear changes associated with apoptosis as assessed by transmission electron microscopy and DNA fragmentation as determined by flow cytometry. Taken together, these data show that apoptosis in HL-60 cells, induced by blocking arachidonate-phospholipid remodeling, is correlated with a redistribution of arachidonate in membrane phospholipids and suggest that such alterations represent a signal which controls the capacity of cells to proliferate.