2-Chloroethanol Induced Upregulation of Matrix Metalloproteinase-2 in Primary Cultured Rat Astrocytes Via MAPK Signal Pathways.

2-Chloroethanol Induced Upregulation of Matrix Metalloproteinase-2 in Primary Cultured Rat Astrocytes Via MAPK Signal Pathways.
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DOI:
10.3389/fnins.2016.00593
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发表时间:
2016
影响因子:
4.3
通讯作者:
Jin Y
Jin Y
中科院分区:
医学2区
文献类型:
--
作者:
Sun Q;Liao Y;Wang T;Tang H;Wang G;Zhao F;Jin Y

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本研究旨在通过关注1,2-二氯乙烷(1,2-DCE)体内代谢产物2-氯乙醇(2-CE)诱导大鼠星形胶质细胞基质金属蛋白酶-2 (MMP-2)的改变来探讨1,2-二氯乙烷(1,2-DCE)诱导脑水肿的机制。通过免疫染色、蛋白质印迹或实时 RT-PCR 分析检测星形胶质细胞中 MMP-2 的蛋白和 mRNA 水平,以及 p38 MAPK (p-p38)、细胞外信号调节蛋白激酶 (p-ERK1/2) 和 c-Jun N 末端激酶 (p-JNK1/2) 的磷酸化蛋白水平。这项研究的结果表明,星形胶质细胞中 MMP-2 的蛋白质水平被 2-CE 上调。同时,2-CE处理的细胞中p-p38、p-ERK1/2和p-JNK1/2的蛋白水平也明显升高。此外,用SB202190(p38 MAPK抑制剂)、U0126(ERK1/2抑制剂)或SP600125(JNK1/2抑制剂)预处理星形胶质细胞可以抑制p-p38、p-ERK1/2和p-JNK1/2的表达上调。由于 p-p38 和 p-JNK1/2 的蛋白水平受到抑制,MMP-2 的蛋白水平也显着降低,表明 MAPK 信号通路的激活参与了 2-CE 诱导的 MMP-2 表达上调的机制。
This study was to explore the mechanisms underlying 1,2-dichloroethane (1,2-DCE) induced brain edema by focusing on alteration of matrix metalloproteinase-2 (MMP-2) in rat astrocytes induced by 2-chloroethanol (2-CE), an intermediate metabolite of 1,2-DCE in vivo. Protein and mRNA levels of MMP-2, and the phosphorylated protein levels of p38 MAPK (p-p38), extracellular signal regulated protein kinase (p-ERK1/2) and c-Jun N-terminal kinase (p-JNK1/2) in astrocytes were examined by immunostaining, western blot or real-time RT-PCR analysis. Findings from this study disclosed that protein levels of MMP-2 were upregulated by 2-CE in astrocytes. Meanwhile, protein levels of p-p38, p-ERK1/2 and p-JNK1/2 were also increased apparently in the cells treated with 2-CE. Moreover, pretreatment of astrocytes with SB202190 (inhibitor of p38 MAPK), U0126 (inhibitor of ERK1/2) or SP600125 (inhibitor of JNK1/2) could suppress the upregulated expression of p-p38, p-ERK1/2, and p-JNK1/2. In response to suppressed protein levels of p-p38 and p-JNK1/2, the protein levels of MMP-2 also decreased significantly, indicating that activation of MAPK signal pathways were involved in the mechanisms underlying 2-CE-induced upregulation of MMP-2 expression.
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