AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD.
AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD.
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DOI：
10.3389/fphys.2015.00085
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发表时间：
2015
影响因子：
4
通讯作者：
Treebak JT
中科院分区：
文献类型：
--
作者：
Brandauer J;Andersen MA;Kellezi H;Risis S;Frøsig C;Vienberg SG;Treebak JT
线粒体蛋白去乙酰化酶sirtuin (SIRT) 3可能介导运动训练诱导的线粒体生物发生的增加和活性氧（ROS）处理的改善。我们确定了运动训练诱导的骨骼肌SIRT3和其他线粒体蛋白丰度增加对amp活化蛋白激酶（AMPK）的需求。6.5周的运动训练增加了野生型（WT, n = 13-15）小鼠股四头肌中SIRT3 （p < 0.01）和超氧化物歧化酶2 （MnSOD, p < 0.05）蛋白的丰度，而AMPK α2激酶死亡（KD, n = 12-13）小鼠则没有增加。我们还观察到，在健康人群中，经过运动训练的骨骼肌中MnSOD丰度有明显增加的趋势（p = 0.051; n = 6）。为了进一步阐明AMPK在这些作用中的作用，我们用5-氨基-1-β- d -核糖呋喃基咪唑-4-羧酰胺（AICAR）治疗WT （n = 7-8）和AMPK α2 KD （n = 7-9）小鼠。每天注射4周AICAR （500 mg/kg）可导致WT小鼠SIRT3 （p < 0.05）和MnSOD （p < 0.01）依赖性升高，但AMPK α2 KD小鼠无明显升高。我们还测试了重复AICAR治疗对缺乏转录辅助激活因子过氧化物酶体增殖物激活受体γ-辅助激活因子1α (PGC-1α KO, n = 9-10)小鼠线粒体蛋白水平的影响。久坐PGC-1α KO小鼠骨骼肌SIRT3和MnSOD蛋白丰度降低（p < 0.01）， aicar诱导的SIRT3和MnSOD蛋白丰度升高仅在WT小鼠中观察到（p < 0.05）。最后，在小鼠或人类骨骼肌中，急性运动对MnSOD （K122）或寡霉素敏感性赋予蛋白（OSCP; K139）上SIRT3靶赖氨酸残基的乙酰化状态没有改变。我们提出AMPK在运动训练中调节骨骼肌线粒体功能和ROS处理中的重要作用。
The mitochondrial protein deacetylase sirtuin (SIRT) 3 may mediate exercise training-induced increases in mitochondrial biogenesis and improvements in reactive oxygen species (ROS) handling. We determined the requirement of AMP-activated protein kinase (AMPK) for exercise training-induced increases in skeletal muscle abundance of SIRT3 and other mitochondrial proteins. Exercise training for 6.5 weeks increased SIRT3 (p < 0.01) and superoxide dismutase 2 (MnSOD; p < 0.05) protein abundance in quadriceps muscle of wild-type (WT; n = 13–15), but not AMPK α2 kinase dead (KD; n = 12–13) mice. We also observed a strong trend for increased MnSOD abundance in exercise-trained skeletal muscle of healthy humans (p = 0.051; n = 6). To further elucidate a role for AMPK in mediating these effects, we treated WT (n = 7–8) and AMPK α2 KD (n = 7–9) mice with 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR). Four weeks of daily AICAR injections (500 mg/kg) resulted in AMPK-dependent increases in SIRT3 (p < 0.05) and MnSOD (p < 0.01) in WT, but not AMPK α2 KD mice. We also tested the effect of repeated AICAR treatment on mitochondrial protein levels in mice lacking the transcriptional coactivator peroxisome proliferator-activated receptor γ-coactivator 1α (PGC-1α KO; n = 9–10). Skeletal muscle SIRT3 and MnSOD protein abundance was reduced in sedentary PGC-1α KO mice (p < 0.01) and AICAR-induced increases in SIRT3 and MnSOD protein abundance was only observed in WT mice (p < 0.05). Finally, the acetylation status of SIRT3 target lysine residues on MnSOD (K122) or oligomycin-sensitivity conferring protein (OSCP; K139) was not altered in either mouse or human skeletal muscle in response to acute exercise. We propose an important role for AMPK in regulating mitochondrial function and ROS handling in skeletal muscle in response to exercise training.
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肿瘤抑制因子 SIRT3 脱乙酰并激活锰超氧化物歧化酶清除 ROS
影响因子：
7.7
作者：
Chen, Yaohui;Zhang, Jinye;Lin, Yan;Lei, Qunying;Guan, Kun-Liang;Zhao, Shimin;Xiong, Yue
通讯作者：
Xiong, Yue
影响因子：
4.8
作者：
Jorgensen, SB;Wojtaszewski, JFP;Pilegaard, H
通讯作者：
Pilegaard, H
DOI：
10.1073/pnas.0705070104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Jaeger, Sibylle;Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
3.3
作者：
Chabi, Beatrice;Adhihetty, Peter J.;Hood, David A.
通讯作者：
Hood, David A.
影响因子：
29
作者：
Cantó C;Jiang LQ;Deshmukh AS;Mataki C;Coste A;Lagouge M;Zierath JR;Auwerx J
通讯作者：
Auwerx J