腺苷酸活化蛋白激酶在酒精性肝病中的研究进展

腺苷酸激活蛋白激酶（AMPK）信号通路是调节细胞能量状态的中心环节,其激活后磷酸化下游的信号分子,抑制ATP合成,同时促进ATP分解,被称为“细胞能量调节器”,在增加脂肪酸氧化、胰岛素敏感性及氧化应激等方面发挥重要作用,可能参与酒精性肝病的发病过程。该文就AMPK在酒精性肝病发病机制中的作用作一综述。     

AMPK信号通路和NLRP3炎症小体在肝衰竭中的研究进展

肝衰竭是由多种因素导致的严重肝脏结构和功能损伤，且是一个涉及“三重打击”的复杂病理生理过程。在机体内，AMPK信号在调节细胞能量平衡中起着重要作用。肝脏作为机体的代谢工厂，对能量的产生和利用有着严格的调控。此外，NLRP3炎症小体也在众多炎症性疾病发生发展过程中扮演着重要角色。而AMPK信号通路和NLRP3小体之间存在交互影响。本文就AMPK介导的多种信号通路、NLRP3炎症小体的激活效应及二者之间的相互作用在肝衰竭过程中的研究进展做一综述。     

AMPK信号通路及其在感染性疾病中的研究进展

腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)是一种AMP依赖性的蛋白激酶,负责调节细胞能量的合成与分解,是细胞生长、繁殖和自噬的关键调节剂。AMPK及其信号通路在病毒、细菌和寄生虫等感染中发挥了重要作用,有望成为一种药物新靶点。本文将对近年来AMPK信号通路在感染性疾病中的研究展开综述。     

腺苷酸激活蛋白激酶在脂肪组织中的作用

腺苷酸激活蛋白激酶（AMPK）是细胞和机体能量代谢的主要调节器。组织缺氧、低血糖、禁食和运动可以激活脂肪细胞中的AMPK。AMPK活化后能通过磷酸化下游信号分子,刺激能量生成途径（葡萄糖转运,脂肪酸氧化）关闭能量消耗的途径（脂肪、蛋白质、糖类的生成）。现在已经明确脂肪组织不仅是能量储存的场所,也在能量平衡以及其它很多过程中发挥作用。研究AMPK与脂肪组织的关系,将为AMPK作为防治肥胖的新靶点提供可靠的理论基础和应用依据。     

腺苷单磷酸激活蛋白激酶参与调控心脏能量代谢的研究进展

腺苷单磷酸激活蛋白激酶(AMPK)是细胞中重要的代谢传感器,主要参与维持代谢应激下能量平衡和氧化还原稳态,与心脏能量代谢密切相关。活化的AMPK可以增强分解代谢、抑制合成代谢、上调ATP水平,也参与调节糖代谢、胆固醇代谢、脂肪酸及蛋白质代谢等过程,为细胞的生长过程提供能量储备;同时活化的AMPK还与新生血管形成、转移、炎症等病理过程息息相关。     

AMPK与肥胖

能量代谢平衡失调是肥胖发生的主要原因。腺苷酸激活蛋白激酶(AMPK)信号通路是调节细胞能量状态的中心环节,其激活后磷酸化下游的信号分子,关闭消耗ATP的合成代谢途径,开启产生ATP的分解代谢途径,被称为"细胞能量调节器",在增加骨骼肌对葡萄糖的摄取、增强胰岛素敏感性、增加脂肪酸氧化以及调节基因转录等方面发挥重要作用。在整体水平,AMPK通过激素和细胞因子如瘦素、脂联素和ghrelin等调节能量的摄入和消耗。研究AMPK与肥胖的关系,将为AMPK作为防治肥胖的新靶点提供可靠的理论基础和应用依据。     

AMPK与糖尿病肾脏疾病

糖尿病肾脏疾病(DKD)的发病机制十分复杂,其发生、发展是在遗传背景基础上多因素综合作用的结果,目前认为高血糖是引起DKD进展的主要原因,炎性反应和氧化应激加速了DKD的病理过程.腺苷酸活化蛋白激酶(AMPK)是“细胞能量调节器”,在调节糖、脂代谢方面起重要作用.AMPK作为一个重要的信号通路,通过参与细胞蛋白质合成、机体炎性反应和氧化应激等过程,在延缓DKD的发生、发展中发挥了重要作用.     

AMPK对缺血心肌保护机制的研究进展

单磷酸腺苷活化的蛋白激酶(AMP-activated protein kinase，AMPK)广泛存在于心肌细胞中，其是细胞的能量感受器，参与细胞能量代谢调节，在生理和病理情况下都发挥着重要的功能。当细胞发生缺血、缺氧等应激反应时，细胞中三磷酸腺苷(ATP)的浓度降低，AMP的浓度升高，AMP/ATP的比例升高，AMPK被激活。激活的AMPK一方面可抑制ATP的消耗，另一方面刺激细胞产生更多的ATP，使细胞内ATP总量增多，从而可有限地延长细胞内ATP的供应时间，发挥对缺血心肌细胞的保护作用。此外，AMPK激活后可抑制蛋白质合成，可能通过减轻内质网应激以减少缺血引起的心肌细胞凋亡，发挥对心肌的保护作用。     

AMP活化蛋白激酶与脂肪细胞因子

腺苷酸活化蛋白激酶(AMPK)作为细胞重要的能量感受器,能通过增强分解代谢通路,抑制合成代谢通路,调节代谢和能量平衡.近年来研究显示AMPK同样参与了以瘦素、脂联素及抵抗素等为代表的脂肪细胞因子生理作用的发挥,同时AMPK激活亦可影响脂肪细胞因子的分泌,因此脂肪细胞因子与AMPK相关作用机制的研究将为治疗肥胖、糖尿病和代谢综合征提供新的途径.     

AMPK与心血管疾病关系研究进展

腺苷酸激活蛋白激酶(AMPK)能感知并调节细胞的能量状态,被称为“细胞能量调节器”.AMPK还能在整体水平通过细胞因子和激素,如瘦素、脂联素等调节机体能量代谢.研究表明AMPK活性紊乱与高血压、心肌肥厚、心力衰竭、动脉粥样硬化、心肌缺血-再灌注损伤等心血管疾病关系密切.此文阐述了AMPK及其与心血管疾病关系,以期为治疗心血管疾病提供新途径.     

Role of 5'AMP-activated protein kinase in skeletal muscle

5'AMP-activated protein kinase (AMPK) is recognized as an important intracellular energy sensor, shutting down energy-consuming processes and turning on energy-generating processes. Discovery of target proteins of AMPK has dramatically increased in the past 10 years. Historically, AMPK was first shown to regulate fatty acid and cholesterol synthesis, but is now hypothesized to take part in the regulation of energy/fuel balance not only at the cellular level but also at the level of the whole organism. In this brief review we will discuss some of the roles of AMPK in skeletal muscle.     

Exercise-induced AMPK activity in skeletal muscle: Role in glucose uptake and insulin sensitivity

The energy/fuel sensor 5′-AMP-activated protein kinase (AMPK) is viewed as a master regulator of cellular energy balance due to its many roles in glucose, lipid, and protein metabolism. In this review we focus on the regulation of AMPK activity in skeletal muscle and its involvement in glucose metabolism, including glucose transport and glycogen synthesis. In addition, we discuss the plausible interplay between AMPK and insulin signaling regulating these processes.     

AMP‐activated protein kinase: a key regulator of energy balance with many roles in human disease

The AMP‐activated protein kinase (AMPK) is a sensor of cellular energy status that regulates cellular and whole‐body energy balance. A recently reported crystal structure has illuminated the complex regulatory mechanisms by which AMP and ADP cause activation of AMPK, involving phosphorylation by the upstream kinase LKB1. Once activated by falling cellular energy status, AMPK activates catabolic pathways that generate ATP whilst inhibiting anabolic pathways and other cellular processes that consume ATP. A role of AMPK is implicated in many human diseases. Mutations in the γ2 subunit cause heart disease due to excessive glycogen storage in cardiac myocytes, leading to ventricular pre‐excitation. AMPK‐activating drugs reverse many of the metabolic defects associated with insulin resistance, and recent findings suggest that the insulin‐sensitizing effects of the widely used antidiabetic drug metformin are mediated by AMPK. The upstream kinase LKB1 is a tumour suppressor, and AMPK may exert many of its antitumour effects. AMPK activation promotes the oxidative metabolism typical of quiescent cells, rather than the aerobic glycolysis observed in tumour cells and cells involved in inflammation, explaining in part why AMPK activators have both antitumour and anti‐inflammatory effects. Salicylate (the major in vivo metabolite of aspirin) activates AMPK, and this could be responsible for at least some of the anticancer and anti‐inflammatory effects of aspirin. In addition to metformin and salicylates, novel drugs that modulate AMPK are likely to enter clinical trials soon. Finally, AMPK may be involved in viral infection: downregulation of AMPK during hepatitis C virus infection appears to be essential for efficient viral replication.     

Targeting AMPK for cardiac protection: opportunities and challenges

AMP-activated protein kinase (AMPK) regulates cellular energy homeostasis and multiple biological processes in cell growth and survival, hence an attractive drug target. AMPK is a heterotrimeric protein consisting of α catalytic, β and γ regulatory subunits; two isoforms of each subunit are present in the heart. Studies using both genetic and pharmacological approaches have demonstrated important roles of AMPK in protecting the heart during ischemia/reperfusion injury as well as in pathological hypertrophy and failure. There is also emerging evidence suggesting isoform-specific function of AMPK, e.g. mutations of the γ2 subunit cause human cardiomyopathy. Thus, strategies avoiding the undesirable effects of altering γ2-AMPK activity, such as isoform selective activation of AMPK may lead to cardioprotective therapies with greater efficacy and safety. This article is part of a special issue entitled “Key Signaling Molecules in Hypertrophy and Heart Failure.”     

AMPK signalling and the control of substrate use in the heart

All mammalian cells rely on adenosine triphosphate (ATP) to maintain function and for survival. The heart has the highest basal ATP demand of any organ due to the necessity for continuous contraction. As such, the ability of the cardiomyocyte to monitor cellular energy status and adapt the supply of substrates to match the energy demand is crucial. One important serine/threonine protein kinase that monitors cellular energy status in the heart is adenosine monophosphate activated protein kinase (AMPK). AMPK is also a key enzyme that controls multiple catabolic and anabolic biochemical pathways in the heart and indirectly plays a crucial role in regulating cardiac function in both physiological and pathophysiological conditions. Herein, we review the involvement of AMPK in myocardial fatty acid and glucose transport and utilization, as it relates to basal cardiac function. We also assess the literature amassed on cardiac AMPK and discuss the controversies surrounding the role of AMPK in physiological and pathophysiological processes in the heart. The work reviewed herein also emphasizes areas that require further investigation for the purpose of eventually translating this information into improved patient care.     

Immunometabolism of AMPK in insulin resistance and atherosclerosis

Obesity leads to insulin resistance and atherosclerosis, which precede Type 2 diabetes and cardiovascular disease. Immunometabolism addresses how metabolic and inflammatory pathways converge to maintain health and a contemporary problem is determining how obesity-induced inflammation precipitates chronic diseases such as insulin resistance and atherosclerosis. AMP-activated protein kinase (AMPK) is an important serine/threonine kinase well known for regulating metabolic processes and maintaining energy homeostasis. However, both metabolic and immunological AMPK-mediated effects play a role in disease. Pro-inflammatory mediators suppress AMPK activity and hinder lipid oxidation. In addition, AMPK activation curbs inflammation by directly inhibiting pro-inflammatory signaling pathways and limiting the build-up of specific lipid intermediates that elicit immune responses. In the context of obesity and chronic disease, these reciprocal responses involve both immune and metabolic cells. Therefore, the immunometabolism of AMPK-mediated processes and therapeutics should be considered in atherosclerosis and insulin resistance.