Lithium-induced teratogenesis in frog embryos prevented by a polyphosphoinositide cycle intermediate or a diacylglycerol analog.
Lithium-induced teratogenesis in frog embryos prevented by a polyphosphoinositide cycle intermediate or a diacylglycerol analog.
复制标题
多磷酸肌醇循环中间体或二酰基甘油类似物可防止锂诱导的青蛙胚胎畸形发生。
DOI：
10.1016/0012-1606(89)90228-5
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发表时间：
1989
影响因子：
2.7
通讯作者：
Gimlich,RL
中科院分区：
文献类型：
--
作者：
Busa,WB;Gimlich,RL
显微注射氯化锂到32细胞的Xenopus胚胎的预期腹侧卵裂球中，引起背前部结构如脊索、神经管、眼睛和水泥腺的重复。我们在这里报告，这种致畸作用的Li+是防止共注射的equimolarmyo-肌醇，中间的聚磷酸肌醇循环。相反，表肌醇，非生物位置异构体的肌醇不采用在这个周期中，是无效的拯救锂+注射胚胎。用肿瘤促进剂，佛波醇肉豆蔻酸酯乙酸酯（聚磷酸肌醇循环衍生的第二信使，甘油二酯的类似物）处理7期胚胎，也可以防止Li+胚胎的背前重复，而非转化类似物，佛波醇肉豆蔻酸酯乙酸酯-4-O-甲基醚，没有效果。这两种拯救剂在单独施用时对发育没有明显的影响（即，不含Li+）。锂离子选择性微电极测量表明，细胞内的锂离子水平是相同的，当锂离子注入或不myo-inositol。克隆分析表明，注射Li+肌醇的卵裂球对后期胚胎的后代贡献正常。由于Li+是一种公认的聚磷酸肌醇循环抑制剂，因此可以对纤维肌肌醇和二酰甘油水平产生深远的影响，这些关于肌醇介导的救援的观察结果表明，改变聚磷酸肌醇循环活性在锂诱导的致畸作用中的作用。
Microinjection of LiCl into prospective ventral blastomeres of the 32-cellXenopusembryo gives rise to duplication of dorsoanterior structures such as the notochord, neural tube, eyes, and cement gland. We report here that this teratogenic effect of Li+is prevented by coinjection of equimolarmyo-inositol, an intermediate of the polyphosphoinositide cycle. In contrast,epi-inositol, a nonbiological positional isomer of inositol not employed in this cycle, is ineffective at rescuing Li+-injected embryos. Treatment of embryos at stage 7 with the tumor promoter, phorbol myristate acetate (an analog of the polyphosphoinositide cycle-derived second messenger, diacylglycerol), also prevents dorsoanterior duplication of Li+embryos, while the nontransforming analog, phorbol myristate acetate-4-O-methyl ether, is without effect. Both of these rescuing agents are without obvious effects on development when administered alone (i.e., without Li+). Li+-selective microelectrode measurements demonstrate that intracellular Li+levels are identical when Li+is injected with or withoutmyo-inositol. Clonal analysis shows that blastomeres injected with Li+plusmyo-inositol make a normal contribution of progeny to the later embryo. Because Li+is a well-established inhibitor of the polyphosphoinositide cycle and can thereby have profound effects on cellularmyo-inositol and diacylglycerol levels, these observations concerning inositol-mediated rescue suggest a role for altered polyphosphoinositide cycle activity in lithium-induced teratogenesis.