The role of pro- and anti-apoptotic molecular interactions in embryonic maldevelopment
The role of pro- and anti-apoptotic molecular interactions in embryonic maldevelopment
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DOI：
10.1034/j.1600-0897.2002.01130.x
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发表时间：
2002-10-01
影响因子：
3.6
通讯作者：
Torchinsky, A
中科院分区：
文献类型：
--
作者：
Toder, V;Carp, H;Torchinsky, A
问题：妊娠丢失和先天性结构异常的发生通常在靶向胚胎和胚外组织中的过度凋亡之前。凋亡刺激激活死亡和存活，信号级联组成的分子作为激活剂和效应器，或凋亡的负调节剂。这些级联反应之间的相互作用决定了暴露于致突变刺激的细胞是死亡还是存活。本文综述了促凋亡分子和抗凋亡分子在胚胎对各种致畸剂的反应中的作用。增强母体免疫系统对这些分子的影响也进行了讨论。研究方法：各种亲和抗凋亡分子在胚胎暴露于各种发育毒物，胚胎发育在糖尿病环境中的功能的数据进行了审查。本研究采用TUNEL法、DNA片段化分析、电迁移率改变分析（EMSA）、荧光分析、免疫组化、Western blot、原位杂交等技术检测不同胚胎和胚外组织中的凋亡，并评价TNF α、caspase、NF-κ B和IkappaB、p53、bcl-2等分子的功能。我们的和其他数据在这篇综述中总结表明，剂量的发育毒物所需的诱导妊娠损失和总的结构异常诱导过度凋亡后不久治疗。根据靶组织的强度和类型，这种细胞凋亡伴随着作为细胞凋亡的激活剂和效应剂（例如半胱天冬酶3、半胱天冬酶8、半胱天冬酶2、p53）或负调节剂（bcl-2、NF-κ B）的分子活性的改变。母体免疫增强，降低诱导和自发妊娠丢失的水平和致畸剂诱导的结构异常的发生率和严重程度，已被证明可以调节这些分子的表达。结论：本综述中的数据表明，参与细胞凋亡调节的TNF α、caspase 3、caspase 8、NF-κ B、p53和bcl-2等分子也可能参与决定胚胎对发育毒物的敏感性。母体免疫增强可以调节这些分子的功能。
PROBLEM: Pregnancy loss and the occurrence of inborn structural anomalies are often preceded by excessive apoptosis in targeted embryonic and extraembryonic tissues. Apoptogenic stimuli activate both death and survival, signaling cascades consisting of molecules acting as activators and effectors, or negative regulators of apoptosis. The interplay between these cascades determines whether the cell which is exposed to an apoptogenic stimulus dies or survives. This review summarizes the functioning of pro- and anti-apoptotic molecules in embryos responding to various teratogens. The effect of potentiation of the maternal immune system on these molecules is also discussed.METHODS OF STUDY: The data on the functioning of various pro- and antiapoptotic molecules in embryos exposed to various developmental toxicants, and embryos developing in a diabetic environment are reviewed. Techniques such as the TUNEL method, DNA fragmentation assay, electromobility shift assay (EMSA), fluorometric assay, immunohistochemistry, Western blot, In situ hybridization, have been used in our studies to detect apoptosis, and evaluate the functioning of molecules such as TNFalpha, caspases, NF-kappaB and IkappaB, p53, and bcl-2 in different embryonic and extraembryonic tissues.RESULTS: Our and other data summarized in this review have demonstrated that the doses of developmental toxicants required to induce pregnancy loss and gross structural anomalies induce excessive apoptosis shortly after treatment. Depending on the intensity and type of targeted tissues, this apoptosis was accompanied by alterations in the activity of the molecules which act as activators and effectors (e.g. caspase 3, caspase 8, caspase 2, p53) or negative regulators (bcl-2, NF-kappaB) of apoptosis. Maternal immunopotentiation, which decreases the level of induced and spontaneous pregnancy loss and the incidence and severity of teratogen-induced structural anomalies has been shown to modulate the expression of these molecules. both in embryonic tissues and at the feto-maternal interface.CONCLUSIONS: The data presented in this review suggest that molecules such as TNFalpha, caspase 3, caspase 8, NF-kappaB, p53 and bcl-2, which are involved in the regulation of apoptosis, may also be involved in determining the sensitivity of the embryo to developmental toxicants. Maternal immunopotentiation may modulate the functioning of these molecules.