AMP-Activated Protein Kinase γ2 to the Rescue in Ischemic Heart.
AMP-Activated Protein Kinase γ2 to the Rescue in Ischemic Heart.
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AMP 激活的蛋白激酶 γ2 可拯救缺血性心脏。
DOI：
10.1161/circresaha.117.311946
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发表时间：
2017
影响因子：
20.1
通讯作者：
Zou,Ming-Hui
中科院分区：
文献类型：
--
作者：
Ding,Ye;Zou,Ming-Hui
1114 Circulation Research 2017年10月27日人类AMPKγ2亚基区域（PRKAG 2突变）。这些去抑制/功能获得突变导致肥厚型心肌病和ECG异常，以及心脏糖原水平增加。11重要的是，给予啮齿动物和恒河猴MK-8722（12，一种所有12种哺乳动物AMPK复合物的强效、直接和变构激活剂）可激活AMPK并导致可逆性心脏肥大，尽管葡萄糖稳态得到改善。然而，MK-8722诱导的心脏肥大与人体中的PRKAG 2突变不同，因为没有ECG异常或心脏糖原沉积。AMPKγ2基因功能获得缺陷和AMPK整体药理学激活的差异表明AMPKγ2可能在心脏中具有独特的作用。在本期《循环研究》中，Cao等人13描述了几种细胞和小鼠模型的建立，以确定γ-AMPK在心脏缺血/再灌注损伤中的亚型特异性作用。在他们的系统中，总AMPK活性没有改变，但复合物仅含有1 γ亚型。在γ2过表达的COS 7（细胞来源于CV-1 [猿猴]）细胞、HEK 293（人胚肾细胞293）细胞和新生大鼠心室肌细胞中，选择性AMPK激活导致AMPKγ2沿着AMPK α2和β1亚基核转位。使用一级氨基酸序列分析，他们进一步鉴定了γ2和γ3亚基中的核定位序列和核输出序列，但在γ1中没有。AMPKγ2的核定位序列和核输出序列的突变使其核转位消失。有趣的是，AMPKγ2主要定位于未受刺激的细胞的胞浆中，并且其核转位依赖于AMPKα2的激活。AMPKα2似乎是AMPKγ2核转运所必需的;抑制AMPK或敲低α2亚基可阻断γ2核转运。
1114 Circulation Research October 27, 2017 region of the human AMPKγ2 subunit (PRKAG2 mutations). These disinhibition/gain-of-function mutations result in hypertrophic cardiomyopathy and ECG abnormalities, as well as increased cardiac glycogen levels. 11 Importantly, administration of MK-8722, 12 a potent, direct, and allosteric activator of all 12 mammalian AMPK complexes, into rodents and rhesus monkeys activates AMPK and causes reversible cardiac hypertrophy despite improved glucose homeostasis. However, MK-8722-induced cardiac hypertrophy is different from PRKAG2 mutation in humans as there are no ECG abnormalities or cardiac glycogen deposition. These discrepancies in genetic gain-of-function AMPKγ2 defects and global pharmacological AMPK activation suggest that AMPKγ2 might have a unique role in heart.In this issue of Circulation Research, Cao et al13 describes the creation of several cellular and mouse models to determine the isoform-specific role of γ-AMPK in cardiac ischemia/reperfusion injury. In their systems, total AMPK activity was unaltered, but the complex contained only 1 γ isoform. In γ2-overexpressing COS7 (cells being CV-1 [simian] in origin) cells, HEK293 (human embryonic kidney cells 293) cells, and neonatal rat ventricular myocytes, selective AMPK activation caused nuclear translocation of AMPKγ2 along with AMPK α2-and β1-subunits. Using primary amino acid sequence analyses, they further identified the nuclear localization sequence and nuclear export sequence in γ2 and γ3 subunits but not in γ1. Nuclear localization sequence and nuclear export sequence mutations in AMPKγ2 abolished its nuclear translocation. Interestingly, AMPKγ2 is mainly localized in the cytosol of unstimulated cells, and its nuclear translocation is dependent on AMPKα2 activation. AMPKα2 seems to be required for AMPKγ2 nuclear transportation; inhibition of AMPK or knockdown of the α2 subunit blocked γ2 nuclear translocation.
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影响因子：
5.5
作者：
W. Wade;C. Dees;T. German;R. Marsh
通讯作者：
R. Marsh
调节小鼠对进食蛋白抗原的肠道和全身免疫反应。
影响因子：
24.5
作者：
S. Strobel;A. Ferguson
通讯作者：
A. Ferguson
影响因子：
5.4
作者：
DALLMAN, MJ;THOMAS, ML;GREEN, JR
通讯作者：
GREEN, JR
DOI：
10.1111/j.1365-2672.1981.tb00874.x
发表时间：
1981-01-01
期刊：
JOURNAL OF APPLIED BACTERIOLOGY
影响因子：
--
作者：
HAZENBERG, MP;BAKKER, M;VERSCHOORBURGGRAAF, A
通讯作者：
VERSCHOORBURGGRAAF, A
大鼠 T 淋巴细胞异质性：使用单克隆抗体分离功能亚群
影响因子：
15.3
作者：
R. White;D. Mason;A. Williams;G. Galfrè;C. Milstein
通讯作者：
C. Milstein