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Mood stabilizing drug lithium increases expression of endoplasmic reticulum stress proteins in primary cultured rat cerebral cortical cells.

机译:情绪稳定药物锂可增加原代培养的大鼠大脑皮层细胞内质网应激蛋白的表达。

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The mood stabilizing drug lithium is a highly effective treatment for bipolar disorder. Previous studies in our laboratory found that chronic treatment with the mood stabilizing drug valproate in rat brain increased the expression of endoplasmic reticulum (ER) stress proteins GRP78, GRP94 and calreticulin. We report here that in primary cultured rat cerebral cortical cells, expression of GRP78, GRP94 and calreticulin are increased not only by valproate, but also by lithium after chronic treatment for 1 week at therapeutically relevant concentrations. However, two other mood stabilizing drugs carbamazepine and lamotrigine had no effect on expression of GRP78, GRP94 or calreticulin. Chronic treatment with lithium for 1 week increased both mRNA and protein levels of ER stress proteins. In contrast to a classic GRP78 inducer thapsigargin, an inhibitor of the ER Ca2+ -ATPase, chronic treatment with lithium or valproate for 1 week modestly increased GRP78 expression in neuronal cells, had no effect on basal intracellular free Ca2+ concentration and does not induce cell death. These results indicate that lithium and valproate may increase expression of GRP78, GRP94 and calreticulin in primary cultured rat cerebral cortical cells without causing cell damage. These results also suggest that the mechanism of GRP78 increase induced by lithium and valproate may be different from that of thapsigargin.
机译:情绪稳定药物锂是治疗躁郁症的高效药物。我们实验室先前的研究发现,在大鼠大脑中长期使用稳定情绪的丙戊酸盐治疗可增加内质网(ER)应激蛋白GRP78,GRP94和钙网蛋白的表达。我们在这里报告说,在原代培养的大鼠大脑皮层细胞中,丙戊酸和慢性锂在治疗相关浓度持续1周后,不仅增加了丙戊酸的含量,而且还增加了锂的GRP78,GRP94和钙网蛋白的表达。但是,另外两种稳定情绪的药物卡马西平和拉莫三嗪对GRP78,GRP94或钙网蛋白的表达没有影响。锂慢性治疗1周可增加ER应激蛋白的mRNA和蛋白水平。与经典的GRP78诱导物毒胡萝卜素相反,ER Ca2 + -ATPase抑制剂用锂或丙戊酸盐长期治疗1周可适度增加神经元细胞中GRP78的表达,对基础细胞内游离Ca2 +浓度没有影响,也不会诱导细胞死亡。这些结果表明,锂和丙戊酸盐可以增加原代培养的大鼠大脑皮层细胞中GRP78,GRP94和钙网蛋白的表达而不会引起细胞损伤。这些结果也表明锂和丙戊酸盐诱导的GRP78增加的机制可能与毒胡萝卜素的机制不同。

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