Papaconstantinou Andriana D, Brown Ken M, Noren Bradley T, McAlister Terence, Fisher Benjamin R, Goering Peter L
Center for Devices and Radiological Health, Food and Drug Administration, Rockville, MD 20857, USA.
Birth Defects Res B Dev Reprod Toxicol. 2003 Dec;68(6):456-64. doi: 10.1002/bdrb.10044.
Cells respond to adverse environmental stimuli by enhancing the expression of specific genes, the products of which include a suite of proteins known as heat shock proteins (hsps), a response often attributed to cellular protection.
In this study, we characterized alterations in hsp expression in chick embryos (Hamburger-Hamilton stage 17, 72 h) exposed in ovo to arsenite (As), mercury (Hg), and cadmium (Cd), known developmental toxicants. Embryos were incubated for 2 h following exposure to 3, 10, 30, or 100 nmol metal, or for 2, 4, 12, or 24 h following treatment with 10 nmol metal.
An enhanced de novo synthesis of 24-, 70-, and 90-kD, 70- and 90-kD, and 70-kD proteins was observed with As, Hg, and Cd treatments, respectively. These responses were transient; apparent rates of protein synthesis were maximal 2-4 h after exposure and returned to control rates by 24 h. Actinomycin D experiments demonstrated that arsenite-induced expression of these proteins is transcriptionally regulated. Immunoblotting experiments identified the 24-, 70-, and 90-kD proteins as the heat shock proteins hsp24, hsp70, and hsp90, respectively. Exposure duration-related abnormalities were noted in the neural tube with all metals and in the ganglia and somites with Cd and As. Retina, allantois, and limb defects were specific to Cd-treated embryos, and branchial arch defects were specific to As-treated embryos.
The data support metal-induced developmental abnormalities, which are preceded by synthesis of stress proteins.
细胞通过增强特定基因的表达来应对不利的环境刺激，这些基因的产物包括一组被称为热休克蛋白（hsps）的蛋白质，这种反应通常被认为具有细胞保护作用。
在本研究中，我们对鸡胚（汉伯格-汉密尔顿17期，72小时）在卵内暴露于已知的发育毒物亚砷酸盐（As）、汞（Hg）和镉（Cd）后热休克蛋白表达的变化进行了表征。胚胎在暴露于3、10、30或100 nmol金属后孵育2小时，或在接受10 nmol金属处理后孵育2、4、12或24小时。
分别观察到As、Hg和Cd处理后24-kD、70-kD和90-kD、70-kD和90-kD以及70-kD蛋白的从头合成增强。这些反应是短暂的；蛋白质合成的表观速率在暴露后2-4小时达到最大值，并在24小时时恢复到对照速率。放线菌素D实验表明，亚砷酸盐诱导的这些蛋白质的表达是受转录调控的。免疫印迹实验分别将24-kD、70-kD和90-kD蛋白鉴定为热休克蛋白hsp24、hsp70和hsp90。所有金属处理均导致神经管出现与暴露持续时间相关的异常，Cd和As处理导致神经节和体节出现异常。视网膜、尿囊和肢体缺陷是Cd处理胚胎特有的，鳃弓缺陷是As处理胚胎特有的。
数据支持金属诱导的发育异常，其之前伴有应激蛋白的合成。
