Bournias-Vardiabasis N, Buzin C H
Teratog Carcinog Mutagen. 1986;6(6):523-36. doi: 10.1002/tcm.1770060606.
Exposure of prokaryotic and eukaryotic cells to heat shock (hyperthermia) or to a number of diverse environmental stresses such as teratogens, anoxia, and inhibitors of oxidative phosphorylation results in the enhanced synthesis of a number of proteins which have been previously referred to as heat shock proteins (hsps). More recently, in view of the diverse types of agents that can induce these proteins, they have also been referred to as stress proteins. This phenomenon is one of the most basic regulatory mechanisms in living organisms. Exposure of Drosophila embryos, larvae, or pupae to these types of stresses also results in a variety of developmental abnormalities in the ensuing adult. Although the function(s) of these heat shock proteins has yet to be determined, they are widely thought to play an important role in cell survival and protection following some types of environmental stress. In our laboratory, we have developed an in vitro assay for detecting agents that act as teratogens, utilizing Drosophila embryonic cultures. Drosophila embryonic cells differentiate in vitro to a number of functional cell types including myotubes and ganglia. A number of drugs that have been shown to act as teratogens in mammals have also been found to inhibit muscle and/or neuron differentiation in Drosophila embryonic cultures. We have examined, by two-dimensional gel electrophoresis, the effects of such teratogens on protein synthesis in Drosophila embryonic cells. Inhibition of muscle and/or neuron differentiation correlates well with the induction of two proteins of about 20 kilodaltons. These are identical to two of the heat shock proteins (hsp 23, 22) as shown by electrophoretic mobilities and peptide mapping by partial proteolysis. Heat shock and other treatments such as exposure to some of the metal ions and ether induces the entire set of seven major heat shock proteins in the Drosophila embryonic cells. Dose-response studies of several teratogens show a correlation between the degree of inhibition of differentiation and the level of induction of hsps. Since heat shock proteins have been suggested as possibly serving a protecting role, our present studies are aimed at identifying the role of hsps in teratogenesis and investigating the differential regulation of heat shock genes in response to different external stimuli.
原核细胞和真核细胞受到热休克（高温）或多种不同的环境压力，如致畸剂、缺氧以及氧化磷酸化抑制剂的影响时，会导致一些蛋白质的合成增加，这些蛋白质以前被称为热休克蛋白（hsps）。最近，鉴于能够诱导这些蛋白质的多种类型的因子，它们也被称为应激蛋白。这种现象是生物体中最基本的调节机制之一。将果蝇胚胎、幼虫或蛹暴露于这些类型的压力下，也会导致随后发育成的成虫出现各种发育异常。尽管这些热休克蛋白的功能尚未确定，但人们普遍认为它们在某些类型的环境压力后对细胞存活和保护起着重要作用。在我们实验室，我们利用果蝇胚胎培养物开发了一种体外检测致畸剂的试验。果蝇胚胎细胞在体外可分化为多种功能细胞类型，包括肌管和神经节。已证明在哺乳动物中起致畸作用的一些药物，也被发现在果蝇胚胎培养物中会抑制肌肉和/或神经元的分化。我们通过二维凝胶电泳研究了这些致畸剂对果蝇胚胎细胞蛋白质合成的影响。肌肉和/或神经元分化的抑制与两种约20千道尔顿蛋白质的诱导密切相关。通过电泳迁移率和部分蛋白酶解的肽图谱分析表明，它们与两种热休克蛋白（hsp 23、22）相同。热休克和其他处理，如暴露于某些金属离子和乙醚，可诱导果蝇胚胎细胞中全套七种主要热休克蛋白。几种致畸剂的剂量反应研究表明，分化抑制程度与热休克蛋白的诱导水平之间存在相关性。由于热休克蛋白被认为可能起到保护作用，我们目前的研究旨在确定热休克蛋白在致畸作用中的作用，并研究热休克基因对不同外部刺激的差异调节。
