中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
“健康与疾病的免疫”国际学术研讨会通知      关于有网站冒充本刊网站的声明
《生命科学》 2014, 26(4): 362-368
能量敏感的AMPK-SIRT1通路与炎症调控
代 洁1,张晓明2,林 玲3,艾 青4,张 力3*
(1 重庆文理学院校医院,重庆 402160;2 湖北中医药大学针灸骨伤学院, 武汉 430061;3 重庆医科大学病理生理学教研室,重庆 400016;4 重庆医科大学生理学教研室,重庆 400016)
腺苷酸活化蛋白激酶(AMP-activated protein kinase, AMPK) 是参与调节细胞能量代谢的关键激酶,也可通过沉默信息调节因子1 (silent information regulator of transcription 1, SIRT1) 依赖的途径发挥抗炎效应。AMPK 激活SIRT1 的机制在于AMPK 促进了SIRT1 的激活因子NAD+ 的生成,并解除了DBC1 对SIRT1活性及p53 对SIRT1 表达的抑制效应;而SIRT1 则通过催化NF-κB、AP-1 和组蛋白的去乙酰化反应而降低转录因子活性、恢复染色质致密构象,这可抑制炎症相关基因的转录。此外,AMPK 激活剂及临床常用降糖药二甲双胍均可通过激活AMPK 而在多种炎症相关性疾病模型中发挥有效保护作用。因而,AMPKSIRT1通路有望成为抗炎治疗的新靶点。
 
Energy-sensitive AMPK-SIRT1 pathway and the regulation of inflammation
DAI Jie1, ZHANG Xiao-Ming2, LIN Ling3, AI Qing4, ZHANG Li3*
(1 Hospital of Chongqing University of Arts and Sciences, Chongqing 402160, China; 2 College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan 430061, China; 3 Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China; 4 Department of Physiology, Chongqing Medical University, Chongqing 400016, China)
AMP-activated protein kinase (AMPK) is a crucial kinase involved in the modulation of cellular energy metabolism, and it also has SIRT1-dependent anti-inflammatory activity. The mechanisms through which AMPK activate SIRT1 include promoting the generation of SIRT1 activator NAD+, relieving the suppressive effects on the activity of SIRT1 by DBC1 and on the expression of SIRT1 by p53. SIRT1 then modulates the inflammatory response through deacetylating nuclear factor kappa B (NF-κB), activator protein 1 (AP-1) and histones, thus leading to suppressed transcriptional activities of transcription factors, altered conformation of chromatin, and eventually, transcriptional repression of inflammation-related genes. In addition, AMPK activator and the clinic antidiabetic metformin have protective benefits in various animal models with inflammation-related disorders through activating AMPK. Thus, AMPK-SIRT1 pathway might become a novel target for anti-inflammatory therapy.
 
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