Evaluation of the role of AMP-activated protein kinase and its downstream targets in mammalian hibernation
Evaluation of the role of AMP-activated protein kinase and its downstream targets in mammalian hibernation
复制标题
DOI：
10.1016/j.cbpb.2005.08.010
复制
发表时间：
2005-12-01
影响因子：
2.2
通讯作者：
Rider, MH
中科院分区：
文献类型：
--
作者：
Horman, S;Hussain, N;Rider, MH
哺乳动物冬眠需要对新陈代谢进行广泛的重组，通常包括代谢率降低 95% 以上、选择性抑制许多消耗 ATP 的代谢活动以及将燃料使用转变为主要依赖于脂质储备的氧化。我们研究了 AMP 激活蛋白激酶 (AMPK) 是否可以在此重组中发挥调节作用。研究人员对十三线地松鼠 (Spermophilus tridecemlineatus) 的五个器官中的 AMPK 活性和多个下游靶标的磷酸化状态进行了评估，并将恒温动物与深度休眠的松鼠进行了比较。与常温对照组相比，冬眠地松鼠的白色脂肪组织中的 AMPK 活性增加了 3 倍，但在肝脏、骨骼肌、棕色脂肪组织或大脑中没有发现激活。使用磷酸特异性抗体进行的免疫印迹显示，在冬眠者的白色脂肪组织、肝脏和大脑中，失活的 Thr56 位点真核延伸因子 2 的磷酸化增加，但在其他组织中则没有。在冬眠者的棕色脂肪组织中，失活的 Ser79 位点乙酰辅酶 A 羧化酶磷酸化显着增加，但在白色脂肪组织中没有看到变化。冬眠动物脂肪组织中激素敏感性脂肪酶 Ser565 AMPK 位点的磷酸化水平没有变化。总之，AMPK 似乎不参与地松鼠冬眠期间发生的代谢重组和/或代谢率降低。 (c) 2005 Elsevier Inc. 保留所有权利。
Mammalian hibernation requires an extensive reorganization of metabolism that typically includes a greater than 95% reduction in metabolic rate, selective inhibition of many ATP-consuming metabolic activities and a change in fuel use to a primary dependence on the oxidation of lipid reserves. We investigated whether the AMP-activated protein kinase (AMPK) could play a regulatory role in this reorganization. AMPK activity and the phosphorylation state of multiple downstream targets were assessed in five organs of thirteen-lined ground squirrels (Spermophilus tridecemlineatus) comparing euthermic animals with squirrels in deep torpor. AMPK activity was increased 3-fold in white adipose tissue from hibernating ground squirrels compared with euthermic controls, but activation was not seen in liver, skeletal muscle, brown adipose tissue or brain. Immunoblotting with phospho-specific antibodies revealed an increase in phosphorylation of eukaryotic elongation factor-2 at the inactivating Thr56 site in white adipose tissue, liver and brain of hibernators, but not in other tissues. Acetyl-CoA carboxylase phosphorylation at the inactivating Ser79 site was markedly increased in brown adipose tissue from hibernators, but no change was seen in white adipose tissue. No change was seen in the level of phosphorylation of the Ser565 AMPK site of hormone-sensitive lipase in adipose tissues of hibernating animals. In conclusion, AMPK does not appear to participate in the metabolic re-organization and/or the metabolic rate depression that occurs during ground squirrel hibernation. (c) 2005 Elsevier Inc. All rights reserved.