Differential sensitivity of mouse neural crest cells to ethanol-induced toxicity
Differential sensitivity of mouse neural crest cells to ethanol-induced toxicity
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DOI：
10.1016/s0741-8329(99)00058-0
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发表时间：
2000-01-01
期刊：
影响因子：
2.3
通讯作者：
Sulik, KK
中科院分区：
文献类型：
--
作者：
Chen, SY;Periasamy, A;Sulik, KK
在小鼠和禽类模型中，神经嵴细胞（NCC）已被确定为与乙醇诱导的致畸性相关的重要靶群体。此外，全胚胎培养小鼠模型在NCC发育早期急性暴露后对乙醇诱导损伤的敏感性显示出品系相关差异。NCC的敏感性差异可能导致了这些菌株差异，但尚未探讨过。为此，比较了对乙醇诱导的致畸性比远交品系（ICR）更敏感的近交系小鼠品系（C57 BL/6 J; C57）的培养NCC。该研究表明，在所有测试的乙醇浓度下，C57 NCC的细胞死亡发生率显著高于ICR菌株的细胞死亡发生率，并且早在初始暴露于100 mM乙醇后12小时。在对照条件下以及在测试的所有剂量和时间下，C57细胞中膜脂质的横向流动性更快，膜GM 1含量低于ICR细胞。乙醇暴露导致膜脂横向流动性显着增加，并在膜GM 1含量的减少，发生在剂量和时间依赖性的方式在NCC从两个菌株。一个显着的相关性被发现之间的GM 1含量和膜脂的横向流动性，膜脂的横向流动性和细胞活力，以及GM 1含量和细胞活力在NCC从两个菌株。这些结果表明，不同的应变敏感性乙醇诱导的致畸性可能在于，至少部分，在菌株间的差异响应的NCC人口和NCC的脆弱性，乙醇诱导的死亡可能与其内源性膜GM 1含量。(C)2000 Elsevier Science Inc. All rights reserved.
Neural crest cells (NCCs) have been identified as an important target population relative to ethanol-induced teratogenicity in both mouse and avian models. Additionally, whole embryo culture mouse models have shown strain-related differences in sensitivity to ethanol-induced damage following acute exposure during early NCC development. That differential sensitivity of NCCs may contribute to these strain differences has been unexplored. For this purpose, cultured NCCs from an inbred mouse strain (C57BL/6J; C57) that is more sensitive to ethanol-induced teratogenicity than an outbred strain (ICR) were compared. This study showed that the incidence of cell death was significantly higher for the C57 NCCs than those from the ICR strain at all ethanol concentrations tested, and as early as 12 hours after initial exposure to 100 mM ethanol. The lateral mobility of the membrane lipids was faster and the membrane GM1 content was lower in C57 cells than ICR cells both under control conditions and at all doses and times tested. Ethanol exposure resulted in significant increases in the membrane lipid lateral mobility, and decreases in the membrane GM1 content that occurred in a dose and time-dependent manner in the NCCs from both strains. A significant correlation was found between the GM1 content and lateral mobility of the membrane lipids, the lateral mobility of membrane lipids and cell viability, as well as the GM1 content and cell viability in the NCCs from both strains. These results suggest that different strain sensitivities to ethanol-induced teratogencity may lie, at least in part, in the interstrain differential response of the NCC population and that the vulnerability of the NCCs to ethanol-induced death may be related to their endogenous membrane GM1 content. (C) 2000 Elsevier Science Inc. All rights reserved.