内分泌
词汇介绍
拓展阅读
解析
activated 英 /'æktɪveɪtɪd/ 美 /'æktə,vetɪd/
释 义 adj. 活性化的；活泼的
v. 使激活；使活动起来；有生气（activate的过去分词）
同根词 active adj. 积极的；活跃的；主动的；有效的；现役的
actively adv. 积极地；活跃地
active n. 主动语态；积极分子
例 句 What I want you to remember is that specific sub-populations of cells get activated, the activation results in a specific response. 我希望你们记住的是，一些特定的细胞亚群受到刺激时，被激活细胞将引起特定的应答。
protein 英 /ˈprəʊtiːn/ 美 /ˈproʊtiːn/
释 义 n. 蛋白质；朊
adj. 蛋白质的
例 句 Each codon either codes for an amino acid or tells the cell to stop making a protein chain.每一个密码子或者编码一种氨基酸，或者告诉这些细胞停止生产这个蛋白质链。
kinase 英 /ˈkaɪneɪz/ 美 /ˈkɪnneɪz/
释 义 n. [生化] 激酶；致活酶
例 句 The scientists successfully identified the small enzyme molecule responsible, a gene called focal adhesion kinase.科学家成功分离出这种小小的酶分子，基因学上称之为局部粘着激酶。
概述
概述
5'AMP 激活的蛋白激酶或AMPK或5'腺苷单磷酸激活的蛋白激酶是一种酶，在细胞能量稳态中发挥作用，主要是在细胞能量达到一定水平时激活葡萄糖和脂肪酸的摄取和氧化。它属于高度保守的真核蛋白质家族，其直向同源物是酵母中的SNF1和植物中的SnRK1。它由三种蛋白质（亚基）组成，它们共同构成一种功能酶，从酵母到人类都是保守的。它在许多组织中表达，包括肝，脑和骨骼肌。
功能
当AMPK磷酸化乙酰辅酶A羧化酶 1（ACC1）或固醇调节元素结合蛋白1c（SREBP1c）时，它会抑制脂肪酸，胆固醇和甘油三酸酯的合成，并激活脂肪酸的摄取和β-氧化。AMPK通过使Rab-GTPase激活蛋白TBC1D1磷酸化来刺激骨骼肌中的葡萄糖摄取，最终使GLUT4囊泡与质膜融合。AMPK通过激活6-磷酸果糖-2-激酶/果糖-2,6-双磷酸酶 2/3的磷酸化和激活糖原磷酸化酶的磷酸化来刺激糖酵解，并通过抑制糖原合成酶的磷酸化来抑制糖原合成。
临床意义
①锻炼/训练：在一次运动或延长训练期间，会发生许多骨骼肌的生化适应，细胞中的葡萄糖摄取被认为是由AMPK激活时部分介导的。此外，可以建议增加一个直接的AMPK的作用的血液供应，刺激和稳定既行受过训练的肌肉细胞血管生成。
②脂质代谢：AMPK调节脂肪酸氧化的关键途径之一是乙酰辅酶A羧化酶的磷酸化和失活。乙酰辅酶A羧化酶（ACC）将乙酰辅酶A转化为丙二酰辅酶A，丙二酰基棕榈酰转移酶1（CPT-1）的抑制剂。CPT-1将脂肪酸运输到线粒体中进行氧化。因此，ACC的失活导致脂肪酸转运增加和随后的氧化。还认为丙二酰辅酶A的降低是丙二酰辅酶A脱羧酶（MCD）的结果，其可以由AMPK调节。MCD是ACC 的拮抗剂，可将丙二酰辅酶A脱羧为乙酰辅酶A，从而导致丙二酰辅酶A减少，CPT-1和脂肪酸氧化增加。AMPK 在肝脏脂质代谢中也起重要作用。
③葡萄糖运输：在运动条件下，血糖水平不一定很高，胰岛素不一定活化，但是肌肉仍然能够吸收葡萄糖，AMPK似乎部分负责运动引起的葡萄糖摄取，观察到运动后，GLUT-4的浓度在质膜中增加，而在微粒体膜中降低，这表明运动促进了水泡状GLUT-4向质膜的转运，急性运动会增加GLUT-4的易位性，而耐力训练会增加可用GLUT-4蛋白质的总量。电收缩和AICA核糖核苷酸（AICAR）处理均可增加灌注的大鼠后肢肌肉中AMPK的活化，葡萄糖的摄取和GLUT-4的易位，从而将运动诱导的葡萄糖摄取与AMPK联系起来。长期AICAR注射模拟了耐力训练的某些效果，也增加了肌肉细胞中GLUT-4 蛋白的总量。
④甲状腺激素：AMPK和甲状腺 激素调节一些相似的过程。Winder和Hardie等人发现，通过甲状腺激素治疗，AMPK的所有亚基都在骨骼肌中增加，尤其是在比目鱼和红色股四头肌中，磷酸-ACC（AMPK活性的标志物）也有所增加。
AMP-Activated Protein Kinase Regulation of the NLRP3 Inflammasome during Aging
复制标题
衰老过程中NLRP3炎症小体的AMP活化蛋白激酶调节
发表时间：2018-01-01
影响指数：9.8
作者： Mario D Cordero
期刊：Trends Endocrinol Metab
AMPK signaling is associated with a decline in the capacity to respond to metabolic alterations during aging and has been shown to be directly involved in several age-associate diseases (Box 1). AMPK is now known to have a protective role in the development of critical cardiac pathologies such as myocardial ischemia, cardiac hypertrophy, diabetic cardiomyopathy, and heart failure and neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Along with the established role of AMPK in cell growth and cell cycle control, it has also been more recently implicated in cancer metabolism, showing a close correlation with the tumor suppressive functions of LKB1 and P53. Additionally, AMPK has been implicated in several age-related disorders with metabolic profiles, such as metabolic syndrome, obesity, and diabetes. Recent findings propose a relevant role for AMPK in the control of inflammation as a result of evidence that AMPK suppresses the activation of the nuclear factor kappa B (NF-kB) system, a key regulator of innate immunity and inflammation, while AMPKa1 and AMPKa2 expression and phosphorylation decrease with advanced age. Recent studies revealed that cartilage-specific AMPKa1 and AMPKa2 conditional knockout (KO) mice and the AMPKa1a2 double KO suffer accelerated severity of surgically induced osteoarthritis and spontaneous aging-associated osteoarthritis in males with increased IL-1b levels. Furthermore, knee cartilage from aged mice has been associated with reduced AMPKa phosphorylation and increased inflammation, showing a role for AMPK in age-associated osteoarthritis. Skeletal muscle AMPK conditional KO in mice has also been shown to induce myopathy with reduced muscle function. However, AMPK reduction or deletion in muscle is not responsible for the body mass and body composition changes, glucose tolerance, or insulin sensitivity associated with aging. AMPKa2 KO mice exhibit accelerated skin aging with accelerated cellular senescence, demonstrating that AMPK has an important role in skin maintenance during aging. Given the important role of AMPK in cardiovascular health, a decrement of AMPK phosphorylation and function could be involved in cardiovascular aging. Experiments with AMPKa2 KO mice showed more pronounced aging-induced cardiac dysfunction with greater susceptibility in those exposed to a high-fat diet.
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