Fukuda A, Ishii Y, Tasaki K, Matsusue K, Ishida T, Oguri K
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Fukuoka Igaku Zasshi. 1999 May;90(5):259-71.
We report here that a highly toxic coplanar polychlorinated biphenyl (PCB), 3,3',4,4',5-pentachlorobiphenyl (PenCB) induces molecular chaperones, HSP70 and HSP90 in liver cytosol of rats. Male Wistar rats received PenCB in corn oil once at a dose of 25 mg/kg i.p. Pair-fed control groups were treated with the vehicle and given the amount of chow matched with that taken by the PenCB-treated animals, and free-fed controls were given the vehicle. The liver cytosolic HSP70 level in rats treated with PenCB was 5-fold higher than those in free-fed controls, though that for pair-fed controls was approximately 2-fold higher than that in free-fed controls. The liver cytosolic HSP90 alpha and HSP90 beta levels were also higher in PenCB-treated rats than in both control groups, but the induction extent was lesser than that for HSP70. Inductive effect on the chaperones was examined with a single different dose of PenCB 0, 0.5, 1.0, 5.0, 10 and 25 mg/kg. Marked induction of the HSP70 level was observed with a minimum dose of PenCB 0.5 mg/kg. The HSP90 alpha level was induced with PenCB-dose dependent manner although the HSP90 beta induction was greatest with a dose of PenCB 5.0 mg/kg. HSP70 and HSP90 are essential for cells under normal conditions and act as molecular chaperones. HSP90 is well known to modulate the function of sex steroid hormone or aromatic hydrocarbon receptors while HSP70 is required for receptor-HSP90 heterocomplex assembly. The role of molecular chaperones may be involved in the endocrine disrupting properties of coplanar PCB and dioxins.
我们在此报告,一种剧毒的共平面多氯联苯(PCB),即3,3',4,4',5-五氯联苯(PenCB),可诱导大鼠肝细胞质中的分子伴侣HSP70和HSP90。雄性Wistar大鼠经腹腔注射一次给予25 mg/kg剂量的PenCB玉米油溶液。配对喂食对照组用溶剂处理,并给予与PenCB处理动物所摄食量匹配的食物量,自由进食对照组给予溶剂。用PenCB处理的大鼠肝脏细胞质中HSP70水平比自由进食对照组高5倍,而配对喂食对照组比自由进食对照组高约2倍。用PenCB处理的大鼠肝脏细胞质中HSP90α和HSP90β水平也高于两个对照组,但诱导程度低于HSP70。用0、0.5、1.0、5.0、10和25 mg/kg的单一不同剂量PenCB检测对分子伴侣的诱导作用。观察到最低剂量0.5 mg/kg的PenCB可显著诱导HSP70水平。HSP90α水平呈PenCB剂量依赖性诱导,尽管HSP90β在PenCB剂量为5.0 mg/kg时诱导作用最大。HSP70和HSP90在正常条件下对细胞至关重要,并作为分子伴侣发挥作用。众所周知,HSP90可调节性类固醇激素或芳烃受体的功能,而HSP70是受体-HSP90异源复合物组装所必需的。分子伴侣的作用可能与共平面PCB和二恶英的内分泌干扰特性有关。