Upregulation of Matrix Metalloproteinase-9 in Primary Cultured Rat Astrocytes Induced by 2-Chloroethanol Via MAPK Signal Pathways.
Upregulation of Matrix Metalloproteinase-9 in Primary Cultured Rat Astrocytes Induced by 2-Chloroethanol Via MAPK Signal Pathways.
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2-氯乙醇通过 MAPK 信号通路诱导原代培养的大鼠星形胶质细胞中基质金属蛋白酶-9 的上调
DOI：
10.3389/fncel.2017.00218
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发表时间：
2017
影响因子：
5.3
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Wang T;Liao Y;Sun Q;Tang H;Wang G;Zhao F;Jin Y
2-氯乙醇（2-CE）是1，2-二氯乙烷（1，2-DCE）在体内的反应性代谢产物之一，可能参与了1，2-二氯乙烷（1，2-DCE）中毒所致脑水肿的形成。本研究旨在探讨丝裂原活化蛋白激酶（MAPK）信号通路在2-CE诱导大鼠星形胶质细胞基质金属蛋白酶-9（MMP-9）表达上调中的作用。采用Western blot和实时荧光定量RT-PCR方法检测大鼠星形胶质细胞p38 MAPK（p38）、细胞外信号调节蛋白激酶（ERK）、c-Jun N-末端激酶（JNK）和MMP-9在蛋白和基因水平的表达。结果显示，2-CE处理后星形胶质细胞MMP-9蛋白和mRNA水平均显著升高。同时，2-CE处理后星形胶质细胞磷酸化p38（p-p38）、ERK 1/2（p-ERK 1/2）和JNK 1/2（p-JNK 1/2）蛋白水平也显著升高。此外，在2-CE作用下，MMP-9的蛋白和mRNA水平均显著降低，提示MAPK信号通路的激活可能在MMP-9转录水平的上调中起重要作用。此外，由于N-乙酰-L-半胱氨酸（NAC），一种强大的抗氧化剂氨基酸，预处理可以减弱MMP-9，p-p38，p-ERK 2和p-JNK 1/2在2-CE暴露的星形胶质细胞中的升高水平，MAPK信号通路的激活可以部分地由活性氧（ROS）介导，这最有可能是在2-CE代谢中产生的。
2-Chloroethanol (2-CE) is one of the reactive metabolites of 1,2-DCE in vivo, which might contribute to brain edema formation induced by 1,2-dichloroethane (1,2-DCE) poisoning. Thus, the purpose of this study was to explore the roles of mitogen-activated protein kinase (MAPK) signal pathways in upregulation of matrix metalloproteinase-9 (MMP-9) in 2-CE exposed rat astrocytes. Expression of p38 MAPK (p38), extracellular signal regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and MMP-9 at both protein and gene levels in rat astrocytes were determined using western blot and real-time RT-PCR methods. The results showed that both protein and mRNA levels of MMP-9 in 2-CE exposed astrocytes significantly increased. Meanwhile, protein levels of phosphorylated p38 (p-p38), ERK1/2 (p-ERK1/2) and JNK1/2 (p-JNK1/2) in 2-CE exposed astrocytes also significantly increased. In addition, both protein and mRNA levels of MMP-9 significantly decreased in response to reduced protein levels of p-p38, p-ERK1/2 and p-JNK1/2 achieved by supplement with their specific inhibitors, indicating that activation of MAPK signal pathways might play an important role in upregulation of MMP-9 expression at the transcriptional level in 2-CE exposed astrocytes. Furthermore, since pretreatment of n-acetyl-l-cysteine (NAC), a powerful antioxidant amino acid, could attenuate the elevated levels of MMP-9, p-p38, p-ERK2 and p-JNK1/2 in 2-CE exposed astrocytes, activation of MAPK signal pathways in 2-CE exposed astrocytes could be mediated partially by reactive oxygen species (ROS), which was most likely generated in the metabolism of 2-CE.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
2.4
作者：
Borders AS;de Almeida L;Van Eldik LJ;Watterson DM
通讯作者：
Watterson DM
影响因子：
4.3
作者：
Liu, Lie-Gang;Yan, Hong;Sun, Xiu-Fa
通讯作者：
Sun, Xiu-Fa
影响因子：
10.5
作者：
Kant, Shashi;Swat, Wojciech;Davis, Roger J.
通讯作者：
Davis, Roger J.
影响因子：
6.1
作者：
Kim, Myungsuk;Park, Young Gyun;Nho, Chu Won
通讯作者：
Nho, Chu Won