Investigations into the Role of Metabolism in the Inflammatory Response of BV2 Microglial Cells.
Investigations into the Role of Metabolism in the Inflammatory Response of BV2 Microglial Cells.
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代谢在BV2小胶质细胞炎症反应中的作用
DOI：
10.3390/antiox10010109
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发表时间：
2021-01-14
期刊：
影响因子：
--
通讯作者：
Maher P
中科院分区：
文献类型：
--
作者：
Maher P
尽管阿尔茨海默病(AD)的特征是淀粉样β斑块和神经原纤维缠结，但越来越多的证据表明，神经炎症、线粒体功能障碍和氧化应激在疾病的发生和发展中发挥着重要作用。阿尔茨海默病的一个主要危险因素是糖尿病，糖尿病的特征还包括氧化应激和线粒体功能障碍以及慢性低度炎症。越来越多的证据表明，在免疫细胞中，促炎症表型的诱导与从氧化磷酸化(OXPHOS)到糖酵解的转变有关。然而，高血糖是否也有助于这种转变尚不清楚。几种不同的方法，包括在不同碳源中培养BV2小胶质细胞，使用酶抑制剂，敲除关键途径元件，并结合细菌脂多糖(LPS)激活来解决这一问题。结果表明，虽然高糖有利于NO的产生，但在驱动OXPHOS的碳源存在时，促炎细胞因子的产生最高。此外，在驱动OXPHOS的碳源中，谷氨酰胺是一种非常有效的IL6产生诱导剂。这种效应在葡萄糖存在时会受到抑制。总之，这些结果可能为糖尿病和阿尔茨海默病背景下的神经炎症的治疗操作提供新的前景。
Although the hallmarks of Alzheimer’s disease (AD) are amyloid beta plaques and neurofibrillary tangles, there is growing evidence that neuroinflammation, mitochondrial dysfunction and oxidative stress play important roles in disease development and progression. A major risk factor for the development of AD is diabetes, which is also characterized by oxidative stress and mitochondrial dysfunction along with chronic, low-grade inflammation. Increasing evidence indicates that in immune cells, the induction of a pro-inflammatory phenotype is associated with a shift from oxidative phosphorylation (OXPHOS) to glycolysis. However, whether hyperglycemia also contributes to this shift is not clear. Several different approaches including culturing BV2 microglial cells in different carbon sources, using enzyme inhibitors and knocking down key pathway elements were used in conjunction with bacterial lipopolysaccharide (LPS) activation to address this question. The results indicate that while high glucose favors NO production, pro-inflammatory cytokine production is highest in the presence of carbon sources that drive OXPHOS. In addition, among the carbon sources that drive OXPHOS, glutamine is a very potent inducer of IL6 production. This effect is dampened in the presence of glucose. Together, these results may provide new prospects for the therapeutic manipulation of neuroinflammation in the context of diabetes and AD.
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DOI：
10.1016/j.bbalip.2014.10.002
发表时间：
2015-04
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Kuhn H;Banthiya S;van Leyen K
通讯作者：
van Leyen K
DOI：
10.7762/cnr.2018.7.4.229
发表时间：
2018-10
期刊：
Clinical nutrition research
影响因子：
--
作者：
Lee HJ;Seo HI;Cha HY;Yang YJ;Kwon SH;Yang SJ
通讯作者：
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影响因子：
8.8
作者：
Lanning NJ;Looyenga BD;Kauffman AL;Niemi NM;Sudderth J;DeBerardinis RJ;MacKeigan JP
通讯作者：
MacKeigan JP
影响因子：
7.3
作者：
Diskin C;Pålsson-McDermott EM
通讯作者：
Pålsson-McDermott EM
影响因子：
2.9
作者：
Maher, Pamela;Salgado, Karmen F.;Lapchak, Paul A.
通讯作者：
Lapchak, Paul A.