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| 1 | Regulation of AMP-activated protein kinase by natural and synthetic activators显示文摘The AMP-activated protein kinase(AMPK)is a sensor of cellular energy status that is almost universally expressed in eukaryotic cells.While it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner,during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level,by responding to hormones that act primarily on the hypothalamus.AMPK monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP,and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be discussed.Given the central importance of energy balance in diseases that are major causes of morbidity or death in humans,such as type 2 diabetes,cancer and inflammatory disorders,there has been a major drive to develop pharmacological activators of AMPK.Many such activators have been described,and the various mechanisms by which these activate AMPK will be discussed.A particularly large class of AMPK activators are natural products of plants derived from traditional herbal medicines.While the mechanism by which most of these activate AMPK has not yet been addressed,I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores,and that many of them will turn out to be inhibitors of mitochondrial function. | David Grahame Hardie | 2016 | Acta Pharmaceutica Sinica B2016，6，1： | 11 |
| 2 | 基于“脾虚致消”理论探讨健脾清热法通过AMPK/mTORC1/SAD-A通路防治糖尿病机制研究设想显示文摘胰岛β细胞功能异常是糖尿病的发病关键,AMPK/mTORC1/SAD-A信号通路参与调控胰岛β细胞的形态和功能。脾虚致消是糖尿病发病的主要病机,健脾清热法是糖尿病的主要治法,并通过调节信号通路改善胰岛β细胞功能。mTORC1位于信号中心双向调控AMPK和SAD-A的活性,mTORC1的枢纽作用与'脾'的功能密切相关,从AMPK/mTORC1/SAD-A信号通路角度探讨胰岛β细胞功能障碍,有助于深入探寻健脾清热法改善胰岛β细胞功能的作用机制,为中医药治疗糖尿病的机制研究提供新的研究方向。 | 黄杰 徐云生 黄延芹 | 2019 | 中华中医药杂志2019，34，3： | 9 |
| 3 | Hierarchical activation of compartmentalized pools of AMPK depends on severity of nutrient or energy stress显示文摘AMPK, a master regulator of metabolic homeostasis, is activated by both AMP-dependent and AMP-independent mechanisms. The conditions under which these different mechanisms operate, and their biological implications are unclear. Here, we show that, depending on the degree of elevation of cellular AMP, distinct compartmentalized pools of AMPK are activated, phosphorylating different sets of targets. Low glucose activates AMPK exclusively through the AMP-independent, AXIN-based pathway in lysosomes to phosphorylate targets such as ACC1 and SREBP1c, exerting early anti-anabolic and pro-catabolic roles. Moderate increases in AMP expand this to activate cytosolic AMPK also in an AXIN-dependent manner. In contrast, high concentrations of AMP, arising from severe nutrient stress, activate all pools of AMPK independently of AXIN. Surprisingly, mitochondrion-localized AMPK is activated to phosphorylate ACC2 and mitochondrial fission factor (MFF) only during severe nutrient stress. Our findings reveal a spatiotemporal basis for hierarchical activation of different pools of AMPK during differing degrees of stress severity. | Yue Zong Chen-Song Zhang Mengqi Li Wen Wang Zhichao Wang Simon A. Hawley Teng Ma Jin-Wei Feng Xiao Tian Qu Qi Yu-Qing Wu Cixiong Zhang Zhiyun Ye Shu-Yong Lin Hai-Long Piao D. Grahame Hardie Sheng-Cai Lin | 2019 | Cell Research2019，29，6： | 8 |
| 4 | LKB1-AMPK-mTOR信号通路在子宫内膜癌的研究现状显示文摘子宫内膜癌(EC)为女性生殖系统3大恶性肿瘤之一,其病因迄今尚未阐明。肝激酶B1(LKB1),又被称为丝氨酸/苏氨酸激酶(STK)11,是肿瘤抑制激酶。在波伊茨-耶格综合征(PJS)患者中,LKB1失去活性。LKB1磷酸化、磷酸AMP活化蛋白激酶(AMPK)激活及哺乳动物西罗莫司靶蛋白(mTOR)抑制,均可抑制包括EC在内的肿瘤细胞增殖及其能量代谢。EC的发生和发展与LKB1-AMPK-mTOR信号通路密切相关。笔者拟阐述LKB1-AMPK-mTOR信号通路对于EC作用的研究现状,以及通过该信号通路治疗EC的最新研究进展。 | 赵玲 尹香花 | 2019 | 中华妇幼临床医学杂志(电子版)2019，15，2： | 4 |
| 5 | 重楼皂苷A直接靶向活化AMPK诱导结直肠癌细胞自噬显示文摘目的:探讨重楼皂苷A(Polyphyllin A,PPA)对结直肠癌细胞自噬的影响及其潜在机制。方法:选用结直肠癌RKO和HRT18细胞株作为细胞模型。用不同浓度PPA处理RKO细胞和HRT18细胞,MTT法检测细胞活力,筛选最佳实验浓度;集落形成实验检测细胞克隆能力;免疫印迹法检测微管相关蛋白LC3-Ⅱ表达、腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)和雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)表达及其磷酸化;免疫荧光检测自噬体形成;分子对接分析PPA与AMPK相互间作用。结果:与0μmol/L组相比,PPA各浓度组细胞活力明显降低(P<0.05)。与0μmol/L组相比,PPA组两株细胞克隆形成能力明显降低(P<0.05);随着PPA浓度逐渐增加,两株细胞中LC3-Ⅱ表达明显上调(P<0.05),自噬体发生聚集,总AMPK、mTOR蛋白无明显变化(P>0.05),而磷酸化AMPK升高、磷酸化mTOR蛋白降低(P<0.05);PPA与AMPK存在直接结合作用。结论:PPA通过直接靶向活化AMPK诱导结直肠癌细胞发生自噬。 | 彭鹏 杨书胜 向雨晨 文君 司渊 刘莹 | 2021 | 江苏大学学报(医学版)2021，31，4： | 4 |
| 6 | Peutz-Jeghers综合征临床及遗传学研究现状显示文摘Peutz-Jeghers综合征(PJS)是一种罕见的遗传性错构瘤性息肉疾病,以皮肤黏膜色素斑沉着、多发消化道错构瘤性息肉和随年龄增长肿瘤易感性增加为特征性表现。目前唯一确定的PJS致病基因为丝氨酸/苏氨酸激酶11(STK11),该基因是一种抑癌基因,在人体几乎所有组织中均表达,且在肿瘤组织中的表达水平显著高于正常组织。STK11基因突变导致STK11蛋白激酶功能障碍是PJS发病的根本原因。PJS患者临床特征不同,基因突变类型多样,建立特定的基因型-表型相关性,实现患者个性化的筛查和治疗,将成为未来的研究热点。 | 张同真 肖年军 宁守斌 孙涛 巫锦程 | 2021 | 医学综述2021，27，11： | 2 |
| 7 | 腺苷酸活化蛋白激酶在神经炎症中的作用显示文摘神经炎症是大脑防御内源性和外源性伤害的生物学过程,主要表现为小胶质细胞激活及T细胞入侵等,但过度的神经炎症反应会导致或加强神经元退行性病变及相关疾病发生发展。腺苷酸活化蛋白激酶(AMPK)活化可在多种神经炎症疾病动物模型中发挥抗炎及神经保护作用,但AMPK在不同的病理条件下可能导致神经系统损伤,因此,根据不同的生物学背景研究AMPK在神经炎症中的具体作用具有重要意义。本文对AMPK的结构和活性调控、AMPK与神经炎症的关系及AMPK影响神经炎症的分子机制进行综述,旨在为神经炎症及神经退行性疾病的基础研究和临床治疗提供新的方法。 | 李灵 丁艳平 邵宝平(指导) | 2021 | 中国免疫学杂志2021，37，6： | 2 |
| 8 | PRKAG2基因突变与心脏的关系显示文摘PRKAG2基因突变与心脏关系密切,可引起类似肥厚型心肌病表现,如心室预激(WPW综合征)、心肌肥厚、心脏传导功能障碍及糖原沉积,被称为PRKAG2心脏综合征。该病为罕见病,属于常染色体显性遗传性疾病,确诊有赖于基因检测。现就近年来PRKAG2基因的功能研究现状做一综述。 | 胡海鹰 张必利 郑兴 | 2018 | 心血管病学进展2018，39，3： | 1 |
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