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铜(II)双(二乙二硫代氨基甲酸盐)通过激活血管内皮细胞中的 p38 MAPK 诱导跨膜硫酸乙酰肝素蛋白聚糖 4 的表达。

Copper(II) Bis(diethyldithiocarbamate) Induces the Expression of Syndecan-4, a Transmembrane Heparan Sulfate Proteoglycan, via p38 MAPK Activation in Vascular Endothelial Cells.

机构信息

Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, Japan.

Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi 274-8510, Japan.

出版信息

Int J Mol Sci. 2018 Oct 24;19(11):3302. doi: 10.3390/ijms19113302.

DOI:10.3390/ijms19113302
PMID:30352976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6274924/
Abstract

Proteoglycans synthesized by vascular endothelial cells are important for regulating cell function and the blood coagulation-fibrinolytic system. Since we recently reported that copper(II) bis(diethyldithiocarbamate) (Cu(edtc)₂) modulates the expression of some molecules involving the antioxidant and blood coagulation systems, we hypothesized that Cu(edtc)₂ may regulate the expression of proteoglycans and examined this hypothesis using a bovine aortic endothelial cell culture system. The experiments showed that Cu(edtc)₂ induced the expression of syndecan-4, a transmembrane heparan sulfate proteoglycan, in a dose- and time-dependent manner. This induction required the whole structure of Cu(edtc)₂-the specific combination of intramolecular copper and a diethyldithiocarbamate structure-as the ligand. Additionally, the syndecan-4 induction by Cu(edtc)₂ depended on the activation of p38 mitogen-activated protein kinase (MAPK) but not the Smad2/3, NF-E2-related factor2 (Nrf2), or epidermal growth factor receptor (EGFR) pathways. p38 MAPK may be a key molecule for inducing the expression of syndecan-4 in vascular endothelial cells.

摘要

血管内皮细胞合成的蛋白聚糖对于调节细胞功能和血液凝固-纤维蛋白溶解系统非常重要。由于我们最近报道了铜(II)双(二乙二硫代氨基甲酸盐)（Cu(edtc)₂）调节一些涉及抗氧化和血液凝固系统的分子的表达，我们假设 Cu(edtc)₂可能调节蛋白聚糖的表达，并使用牛主动脉内皮细胞培养系统检验了这一假设。实验表明，Cu(edtc)₂以剂量和时间依赖的方式诱导跨膜硫酸乙酰肝素蛋白聚糖-连接蛋白-4 的表达。这种诱导需要 Cu(edtc)₂的整个结构-分子内铜和二乙二硫代氨基甲酸盐结构的特定组合-作为配体。此外，Cu(edtc)₂诱导的连接蛋白-4 的表达依赖于 p38 丝裂原活化蛋白激酶（MAPK）的激活，但不依赖于 Smad2/3、核因子-E2 相关因子 2（Nrf2）或表皮生长因子受体（EGFR）途径。p38 MAPK 可能是诱导血管内皮细胞中连接蛋白-4 表达的关键分子。

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