Effects of prenatal exposure to ethanol on the cyclin-dependent kinase system in the developing rat cerebellum
Effects of prenatal exposure to ethanol on the cyclin-dependent kinase system in the developing rat cerebellum
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DOI：
10.1016/s0165-3806(02)00573-4
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发表时间：
2002-12-15
期刊：
影响因子：
--
通讯作者：
Luo, J
中科院分区：
文献类型：
--
作者：
Li, Z;Miller, MW;Luo, J
胎儿期暴露于乙醇会抑制发育中小脑的神经发生。细胞周期蛋白依赖性激酶（Cyclin-dependent kinases，CDK）是一类在细胞增殖、分化和存活调节中发挥多种作用的蛋白激酶家族。CDK的活性受CDK激活剂、细胞周期蛋白的正调节，受CDK抑制剂（CDKIs）的负调节。我们推测，妊娠期乙醇暴露引起的小脑发育受损是由CDK系统的破坏介导的。妊娠大鼠自由采食。含乙醇的液体饮食（Et）或成对喂食等热量对照饮食（Ct）。从幼仔（出生后（P）0天至P21）收集小脑，并使用定量免疫印迹程序检查CDK、细胞周期蛋白或CDKI表达。在CT处理的大鼠中，CDK 2及其激活剂cyclin A的表达与颗粒细胞增殖的模式相一致。产前酒精。暴露导致CDK 2/cyclin A表达显著下调。虽然CDK 4/CDK 6及其激活剂cyclin D2的表达在出生后的发育过程中并没有波动，但在ET处理的幼仔中，它们的表达显著增加（P
Prenatal exposure to ethanol inhibits neurogenesis in the developing cerebellum. Cyclin-dependent kinases (CDKs) are a family of protein kinases that play multiple roles in the regulation of cell proliferation, differentiation and survival. The activity of CDKs is positively regulated by CDK activators, cyclins, and negatively regulated by CDK inhibitors (CDKIs). We hypothesize that impaired cerebellar development induced by gestational ethanol exposure is mediated by disruption of the CDK system. Pregnant rats were fed ad libitum with an. ethanol-containing liquid diet (Et) or pair-fed an isocaloric control diet (Ct). Cerebella were collected from pups (postnatal day (P) 0 through P21) and examined for CDK, cyclin, or CDKI expression using a quantitative immunoblotting procedure. In Ct-treated rats, the expression of CDK2 and its activator, cyclin A, paralleled the pattern of granule cell proliferation. Prenatal ethanol. exposure produced a significant down-regulation of CDK2/cyclin A expression. Although the amounts of CDK4/CDK6 and their activator, cyclin D2, did not oscillate during postnatal development, their expression in Et-treated pups was significantly (P