Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs

文化大學機構典藏 CCUR > 環境規劃暨生物資源學院 > 農學院 > 生物科技研究所 > 期刊論文 > Item 987654321/35977

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: https://irlib.pccu.edu.tw/handle/987654321/35977

题名:	Metformin activation of AMPK suppresses AGE-induced inflammatory response in hNSCs
作者:	Chung, MM (Chung, Ming-Min) Nicol, CJ (Nicol, Christopher J.) Cheng, YC (Cheng, Yi-Chuan) Lin, KH (Lin, Kuan-Hung) Chen, YL (Chen, Yen-Lin) Pei, D (Pei, Dee) Lin, CH (Lin, Chien-Hung) Shih, YN (Shih, Yi-Nuo) Yen, CH (Yen, Chia-Hui) Chen, SJ (Chen, Shiang-Jiuun) Huang, RN (Huang, Rong-Nan) Chiang, MC (Chiang, Ming-Chang)
贡献者:	生科所
关键词:	AMPK Metformin AGE Inflammatory response hNSCs
日期:	2017-03
上传时间:	2017-04-19 15:46:31 (UTC+8)
摘要:	A growing body of evidence suggests type 2 diabetes mellitus (T2DM) is linked to neurodegenerative diseases such as Alzheimer's disease (AD). Although the precise mechanisms remain unclear, T2DM may exacerbate neurodegenerative processes. AMP-activated protein kinase (AMPK) signaling is an evolutionary preserved pathway that is important during homeostatic energy biogenesis responses at both the cellular and whole-body levels. Metformin, a ubiquitously prescribed anti-diabetic drug, exerts its effects by AMPK activation. However, while the roles of AMPK as a metabolic mediator are generally well understood, its performance in neuroprotection and neurodegeneration are not yet well defined. Given hyperglycemia is accompanied by an accelerated rate of advanced glycosylation end product (AGE) formation, which is associated with the pathogenesis of diabetic neuronal impairment and, inflammatory response, clarification of the role of AMPK signaling in these processes is needed. Therefore, we tested the hypothesis that metformin, an AMPK activator, protects against diabetic AGE induced neuronal impairment in human neural stem cells (hNSCs). In the present study, hNSCs exposed to AGE had significantly reduced cell viability, which correlated with elevated inflammatory cytokine expression, such as IL-l alpha,IL-1 beta, IL-2, IL-6, IL-12 and TNF-alpha. Co-treatment with metformin significantly abrogated the AGE-mediated effects in hNSCs. In addition, metformin rescued the transcript and protein expression levels of acetyl-CoA carboxylase (ACC) and inhibitory kappa B kinase (IKK) in AGE-treated hNSCs. NF-B-K is a transcription factor with a key role in the expression of a variety of genes involved in inflammatory responses, and metformin did prevent the AGE-mediated increase in NF-B-K mRNA and protein levels in the hNSCs exposed to AGE. Indeed, co-treatment with metformin significantly restored inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) levels in AGE-treated hNSCs. These findings extend our understanding of the central role of AMPK in AGE induced inflammatory responses, which increase the risk of neurodegeneration in diabetic patients.
關聯:	EXPERIMENTAL CELL RESEARCH 卷: 352 期: 1 頁碼: 75-83
显示于类别:	[生物科技研究所 ] 期刊論文

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	350	检视/开启

检视Licence

在CCUR中所有的数据项都受到原著作权保护.

数据加载中.....