Altered expression of BCl2, Bad and Bax mRNA occurs in the rat cerebellum within hours after ethanol exposure on postnatal day 4 but not on postnatal day 9
Altered expression of BCl2, Bad and Bax mRNA occurs in the rat cerebellum within hours after ethanol exposure on postnatal day 4 but not on postnatal day 9
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DOI：
10.1016/j.molbrainres.2004.06.034
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发表时间：
2004-10-22
期刊：
影响因子：
--
通讯作者：
Light, KE
中科院分区：
文献类型：
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作者：
Ge, Y;Belcher, SA;Light, KE
先前的研究表明，乙醇暴露在脆弱的出生后（PN）的第4-6天期间的结果在剂量依赖性的浦肯野神经元细胞凋亡的损失。虽然乙醇的作用机制和浦肯野细胞脆弱性的原因是未知的，我们假设，在PN 4 -6脆弱期浦肯野细胞依赖于活性营养因子抑制凋亡。此外，乙醇用于阻止这种营养信号的接收，导致包括Bcl 2基因家族中蛋白质的特异性改变的凋亡途径的执行。在此脆弱期（即PN 9）之后发生的乙醇暴露预计不会显示这些凋亡蛋白的改变，因为浦肯野细胞不再显示对乙醇的脆弱性。目前的研究是为了确定在PN 4或PN 9乙醇给药后的最初几个小时内Bcl 2家族成员的mRNA表达的变化。采用半定量逆转录聚合酶链反应（PCR）技术检测促凋亡因子Bad、Bax和抗凋亡因子Bcl（2）mRNA的表达水平。在PN 4上以四种不同剂量（1.5、3.0、4.5和6.0 g/kg）给予乙醇，并在处理后1、4、6和8 h进行全小脑mRNA分析。剂量大于1.5 g/kg在处理后8小时内产生Bcl（2）的显著降低和Bad和Bax mRNA的显著增加。与此形成鲜明对比的是，当以3.0或6.0 g/kg的乙醇给予PN 9幼仔时，在处理后1小时或4小时，未发现这些凋亡因子的显著变化。这些结果与我们的假设一致，并为我们的假设提供了进一步的支持，即乙醇中断了对细胞凋亡的主动抑制，这是浦肯野细胞在这段时间内脆弱性的一个重要特征。(C)2004 Elsevier B. V.保留所有权利。
Previous studies have demonstrated that ethanol exposure during the vulnerable postnatal (PN) day 4-6 period results in a dose-dependent loss of Purkinje neurons in rats by apoptosis. Although the mechanism of ethanol action and the reasons for Purkinje cell vulnerability are unknown, we hypothesize that during the PN4-6 vulnerable period Purkinje cells are dependent on active trophic factor suppression of apoptosis. Furthermore, ethanol acts to prevent the reception of this trophic signaling resulting in the execution of the apoptotic pathway that includes specific alterations of proteins in the Bcl2 gene family. Ethanol exposure that occurs after this vulnerable period (i.e. PN9) would not be expected to demonstrate alterations in these apoptotic proteins since the Purkinje cells no longer demonstrate vulnerability to ethanol. The current study was undertaken to identify the alterations in mRNA expression for members of the Bcl2-family within the initial hours following ethanol administration on PN4 or PN9. Semi-quantitative reverse transcriptase with polymerase chain reaction (PCR) techniques were used to determine the expression levels of pro-apoptotic factors Bad and Bax, and anti-apoptotic Bcl(2) mRNA. Ethanol was administered at four different doses (1.5, 3.0, 4.5, and 6.0 g/kg) on PN4 and analyses of whole cerebellar mRNA was conducted at 1, 4, 6, and 8 h after treatment. Doses greater than 1.5 g/kg produced significant decreases in Bcl(2) and significant increases in Bad and Bax mRNA during the 8-h period after treatment. In stark contrast, when ethanol was administered at 3.0 or 6.0 g/kg to PN9 pups, no significant alterations of these apoptotic factors were identified at either I or 4 h after treatment. These results are in agreement with and provide further support for our hypothesis that ethanol interrupts the active suppression of apoptosis that is a crucial feature of Purkinje cell vulnerability during this time period. (C) 2004 Elsevier B.V. All rights reserved.