Metformin has adenosine-monophosphate activated protein kinase (AMPK)-independent effects on LPS-stimulated rat primary microglial cultures

被引:0
作者
Labuzek, Krzysztof [1 ]
Liber, Sebastian [1 ]
Gabryel, Bozena [2 ]
Okopien, Boguslaw [1 ]
机构
[1] Med Univ Silesia, Dept Internal Med & Clin Pharmacol, PL-40752 Katowice, Poland
[2] Med Univ Silesia, Dept Pharmacol, PL-40752 Katowice, Poland
关键词
metformin; AMPK; microglia; inflammation; ANTIDIABETIC DRUG METFORMIN; NITRIC-OXIDE SYNTHASE; MITOCHONDRIAL BIOGENESIS; MOUSE MODEL; TNF-ALPHA; INFLAMMATORY CYTOKINES; ALZHEIMERS-DISEASE; SIGNALING PATHWAYS; GLIAL-CELLS; EXPRESSION;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The results of recent studies suggest that metformin, in addition to its efficacy in treating type 2 diabetes, may also have therapeutic potential for the treatment of neuroinflammatory diseases in which reactive microglia play an essential role. However, the molecular mechanisms by which metformin exerts its anti-inflammatory effects remain largely unknown. Adenosine-monophosphate-activated protein kinase (AMPK) activation is the most well-known mechanism of metformin action; however, some of the biological responses to metformin are not limited to AMPK activation but are mediated by AMPK-independent mechanisms. In this paper, we attempted to evaluate the effects of metformin on unstimulated and LPS-activated rat primary microglial cell cultures. The presented evidence supports the conclusion that metformin-activated AMPK participates in regulating the release of TNF-alpha. Furthermore, the effects of metformin on the release of IL-1 beta, IL-6, IL-10, TGF-beta, NO, and ROS as well as on the expression of arginase I, iNOS, NF-kappa B p65 and PGC-1 alpha were not AMPK-dependent, because pretreatment of LPS-activated microglia with compound C, a pharmacological inhibitor of AMPK, did not reverse the effect of metformin. Based on the present findings, we propose that the shift of microglia toward alternative activation may underlie the beneficial effects of metformin observed in animal models of neurological disorders.
引用
收藏
页码:827 / 848
页数:22
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