Wijeweera J B, Thomas C M, Gandolfi A J, Brendel K
Department of Anesthesiology, College of Medicine, University of Arizona, Tucson 85724, USA.
Toxicology. 1995 Dec 15;104(1-3):35-45. doi: 10.1016/0300-483x(95)03119-z.
The present study was undertaken to investigate the usefulness of stress proteins as early, sensitive indicators of hepatotoxicity. Induction of stress protein synthesis in precision-cut rat liver slices was examined following in vitro exposure to sodium arsenite or heat shock. Precision-cut rat liver slices were incubated with 10(-5) or 10(-6) M sodium arsenite for 2, 4 or 8 h in the presence of 35S-methionine or exposed to hyperthermia (42.5 +/- 0.5 degrees C) for 45 min and then incubated with 35S-methionine for 2, 4 or 8 h. Fluorographic analysis indicated an increase in the synthesis of HSP 70 and HSP 90 family of proteins by both treatments. Immunoblot analysis demonstrated that there was a specific induction of HSP 72 and HSP 90. Induction of HSP 70 was greater than that of HSP 90 by both treatments. Stress protein induction occurred at earlier times by concentrations of arsenite which did not alter other viability parameters such as leakage of intracellular K+ or total protein synthesis. The results indicated that induction of stress proteins has the potential usefulness as an early biomarker of arsenite toxicity.
本研究旨在探讨应激蛋白作为肝毒性早期敏感指标的实用性。在体外暴露于亚砷酸钠或热休克后，检测精确切割的大鼠肝切片中应激蛋白合成的诱导情况。将精确切割的大鼠肝切片在含有35S-甲硫氨酸的情况下，与10(-5)或10(-6)M亚砷酸钠孵育2、4或8小时，或暴露于高温（42.5±0.5℃）45分钟，然后与35S-甲硫氨酸孵育2、4或8小时。荧光自显影分析表明，两种处理均使HSP 70和HSP 90家族蛋白的合成增加。免疫印迹分析表明，HSP 72和HSP 90有特异性诱导。两种处理中，HSP 70的诱导均大于HSP 90。亚砷酸钠浓度在未改变其他活力参数（如细胞内K+泄漏或总蛋白合成）的情况下，能在更早时间诱导应激蛋白。结果表明，应激蛋白的诱导作为亚砷酸盐毒性的早期生物标志物具有潜在的实用性。
