Chronic valproate treatment increases expression of endoplasmic reticulum stress proteins in the rat cerebral cortex and hippocampus
Chronic valproate treatment increases expression of endoplasmic reticulum stress proteins in the rat cerebral cortex and hippocampus
复制标题
DOI：
10.1016/s0006-3223(00)00878-7
复制
发表时间：
2000-10-01
影响因子：
10.6
通讯作者：
Young, LT
中科院分区：
文献类型：
--
作者：
Chen, B;Wang, JF;Young, LT
背景：丙戊酸钠是一种治疗双相情感障碍的高效药物，但其作用机制尚不清楚。我们最近利用差异显示聚合酶链式反应发现丙戊酸调节大鼠大脑皮层内质网应激蛋白GRP78的表达。在我们的研究中，我们研究了丙戊酸钠对内质网应激蛋白家族其他成员GRP94和钙网蛋白的影响，并研究了GRP78、GRP94和钙网蛋白在脑内的区域分布。方法：用免疫组织化学方法检测丙戊酸钠(300 mg/kg，腹腔注射)后大鼠特定脑区GRP78、GRP94和钙网蛋白的表达水平。结果：我们报道了丙戊酸盐慢性治疗后内质网应激蛋白家族的其他成员如GRP94和钙网蛋白的表达增加。这三种蛋白在脑内的分布相似，在额叶皮质、顶叶皮质和海马CA1区有明显的增加。结论：由于GRP78、GRP94和钙网蛋白具有分子伴侣活性，并结合内质网中的钙离子，丙戊酸盐的药理作用可能涉及其中一个或多个过程。(C)2000年生物精神病学学会。
Background: Sodium valproate is a highly effective treatment for bipolar disorder, but its mechanism of action remains poorly understood. We recently found with differential display polymerase chain reaction that valproate regulates the expression of the endoplasmic reticulum stress protein GRP78 in the rat cerebral cortex. In our study, we investigated the effect of this drug on the other members of the endoplasmic reticulum stress protein family, GRP94 and calreticulin, and we studied the brain regional distribution of GRP78, GRP94, and calreticulin.Methods: Immunohistochemistry was used to measure protein levels of GRP78, GRP94, and calreticulin after treatment with sodium valproate (300 mg/kg, intraperitoneal) in specific rat brain regions.Results: We report here that chronic treatment with valproate also increased expression of other members of the endoplasmic reticulum stress protein family, such as GRP94 and calreticulin. The brain regional distribution of these changes was similar for all three proteins, with marked increase detected in the frontal cortex, parietal cortex, and CAI region of the hippocampus.Conclusions: Because GRP78, GRP94, and calreticulin possess molecular chaperone activity and bind Ca2+ in the endoplasmic reticulum, the pharmacologic action of valproate may involve one or more of these processes. (C) 2000 Society of Biological Psychiatry.