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钙诱导 SH-SY5Y 和 HEK-293 细胞胞质凝胶蛋白的表达。

Calcium induces expression of cytoplasmic gelsolin in SH-SY5Y and HEK-293 cells.

机构信息

Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA.

出版信息

Neurochem Res. 2010 Jul;35(7):1075-82. doi: 10.1007/s11064-010-0157-8. Epub 2010 Mar 26.

Abstract

Gelsolin plays an important role in the regulation of amyloid beta-protein fibrillogenesis. We report here that calcium ionophore A23187 induces the expression of cytoplasmic gelsolin (c-gelsolin), and that protein kinase C (PKC) is involved in the up-regulation of c-gelsolin. In the presence of calcium, both SH-SY5Y and HEK-293 cells upon treatment with A23187 showed an increase in c-gelsolin expression in a concentration-dependent manner. Calcium-mediated up-regulation of c-gelsolin was inhibited by cycloheximide (a general inhibitor of protein synthesis). When cells were pretreated with staurosporine (an inhibitor of a variety of protein kinases including PKC), the up-regulation of c-gelsolin induced by A23187 was inhibited. Calphostin C, an inhibitor of PKC, blocked the up-regulation of c-gelsolin induced by A23187, while inhibitors of mitogen-activated protein kinases had no effect on c-gelsolin expression. In addition, phorbol-12-myristate-13-acetate, an activator of PKC, up-regulated c-gelsolin expression. These results suggest that calcium mediates up-regulation of c-gelsolin in a PKC-dependent manner.

摘要

凝胶蛋白在调节淀粉样β-蛋白纤维形成中起着重要作用。我们在此报告钙离子载体 A23187 诱导细胞质凝胶蛋白(c-凝胶蛋白)的表达,并且蛋白激酶 C(PKC)参与 c-凝胶蛋白的上调。在存在钙的情况下,A23187 处理的 SH-SY5Y 和 HEK-293 细胞均以浓度依赖性方式显示 c-凝胶蛋白表达增加。钙介导的 c-凝胶蛋白上调被环己酰亚胺(蛋白合成的通用抑制剂)抑制。当用 staurosporine(包括 PKC 在内的多种蛋白激酶的抑制剂)预处理细胞时,A23187 诱导的 c-凝胶蛋白上调被抑制。钙调蛋白 C,PKC 的抑制剂,阻断了 A23187 诱导的 c-凝胶蛋白的上调,而丝裂原激活的蛋白激酶抑制剂对 c-凝胶蛋白表达没有影响。此外,佛波醇 12-肉豆蔻酸 13-乙酸酯,PKC 的激活剂,上调 c-凝胶蛋白的表达。这些结果表明,钙以 PKC 依赖性方式介导 c-凝胶蛋白的上调。

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