Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation.
Glutathione S-transferases Control astrocyte activation and neuronal health during neuroinflammation.
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DOI：
10.3389/fmolb.2022.1080140
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
谷胱甘肽S-转移酶（GST）是外源性物质代谢的II相解毒酶，在脑中容易表达。然而，目前关于它们在大脑中的作用的知识是有限的。我们最近发现GSTM 1促进星形胶质细胞产生促炎介质，并在急性脑炎症期间增强小胶质细胞活化。在这里，我们报告GSTM 1显着影响星形胶质细胞中的TNF-α依赖的转录程序，并调节神经元的活动和应激在脑炎症。我们发现星形胶质细胞中GSTM 1的表达减少会下调促炎基因的表达，同时上调干扰素反应和脂肪酸代谢相关基因的表达。我们的数据还显示，星形胶质细胞中GSTM 1的减少增加了神经元的应激水平，减弱了LPS诱导的脑炎症过程中的神经元活动。此外，我们发现GSTM 1在衰老小鼠的额叶皮层和海马中的表达增加。因此，这项研究进一步推进了我们对脑炎症过程中星形胶质细胞中Glucose S-转移酶作用的理解，并为未来的研究铺平了道路，以确定GSTM 1在炎症和衰老反应性星形胶质细胞反应中的关键作用。
Glutathione S-transferases (GST) are phase II detoxification enzymes of xenobiotic metabolism and readily expressed in the brain. Nevertheless, the current knowledge about their roles in the brain is limited. We have recently discovered that GSTM1 promotes the production of pro-inflammatory mediators by astrocytes and enhances microglial activation during acute brain inflammation. Here we report that GSTM1 significantly affects TNF-α-dependent transcriptional program in astrocytes and modulates neuronal activities and stress during brain inflammation. We have found that a reduced expression of GSTM1 in astrocytes downregulates the expression of pro-inflammatory genes while upregulating the expression of genes involved in interferon responses and fatty acid metabolism. Our data also revealed that GSTM1 reduction in astrocytes increased neuronal stress levels, attenuating neuronal activities during LPS-induced brain inflammation. Furthermore, we found that GSTM1 expression increased in the frontal cortex and hippocampus of aging mice. Thus, this study has further advanced our understanding of the role of Glutathione S-transferases in astrocytes during brain inflammation and paved the way for future studies to determine the critical role of GSTM1 in reactive astrocyte responses in inflammation and aging.
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影响因子：
3.7
作者：
Tan, Hui Ming;Low, Wai Yee
通讯作者：
Low, Wai Yee
影响因子：
2.7
作者：
Neuner, Sarah M.;Wilmott, Lynda A.;Hoffmann, Brian R.;Mozhui, Khyobeni;Kaczorowski, Catherine C.
通讯作者：
Kaczorowski, Catherine C.
影响因子：
25
作者：
通讯作者：
--
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.4061/2010/876940
发表时间：
2010-06-13
期刊：
Human genomics and proteomics : HGP
影响因子：
--
作者：
Josephy PD
通讯作者：
Josephy PD