Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
Comp Biochem Physiol C Toxicol Pharmacol. 2013 Sep;158(3):165-72. doi: 10.1016/j.cbpc.2013.07.006. Epub 2013 Aug 3.
Heat shock proteins (HSPs) are molecular chaperones that aid in protein folding, translocation and in preventing stress-induced protein aggregation. The present study examined the effect of simultaneous sodium arsenite and cadmium chloride treatment on the pattern of HSP30 and HSP70 accumulation in A6 kidney epithelial cells of the frog, Xenopus laevis. Immunoblot analysis revealed that HSP30 and HSP70 accumulation in concurrent stressor treatments were significantly higher than the sum of HSP30 or HSP70 accumulation in individual treatments. This finding suggested a synergistic action between sodium arsenite and cadmium chloride. KNK437 inhibitor studies indicated that the combined stressor-induced accumulation of HSPs may be regulated, at least in part, at the level of transcription. Immunocytochemistry revealed that simultaneous treatment of cells with the two stressors induced HSP30 accumulation primarily in the cytoplasm in a punctate pattern with some dysregulation of F-actin structure. Increased ubiquitinated protein accumulation was observed with combined sodium arsenite and cadmium chloride treatment compared to individual stressors suggesting an impairment of the ubiquitin proteasome degradation system. The addition of a mild heat shock further enhanced the accumulation of HSP30 and HSP70 in response to relatively low concentrations of sodium arsenite plus cadmium chloride.
热休克蛋白（HSPs）是分子伴侣，有助于蛋白质折叠、易位和防止应激诱导的蛋白质聚集。本研究探讨了同时亚砷酸钠和氯化镉处理对非洲爪蟾（Xenopus laevis）A6 肾上皮细胞中 HSP30 和 HSP70 积累模式的影响。免疫印迹分析显示，在并发应激源处理中 HSP30 和 HSP70 的积累明显高于单独处理中 HSP30 或 HSP70 的积累之和。这一发现表明亚砷酸钠和氯化镉之间存在协同作用。KNK437 抑制剂研究表明，联合应激诱导的 HSP 积累可能至少部分受到转录水平的调节。免疫细胞化学显示，同时用两种应激源处理细胞会导致 HSP30 主要在细胞质中以点状模式积累，同时 F-肌动蛋白结构出现一些失调。与单独的应激源相比，联合使用亚砷酸钠和氯化镉处理会导致泛素化蛋白积累增加，这表明泛素蛋白酶体降解系统受到损害。温和热休克的加入进一步增强了 HSP30 和 HSP70 的积累，以响应相对较低浓度的亚砷酸钠加氯化镉。
