Acetylation and deacetylation--novel factors in muscle wasting.
Acetylation and deacetylation--novel factors in muscle wasting.
复制标题
DOI：
10.1016/j.metabol.2012.03.019
复制
发表时间：
2013-01
影响因子：
9.8
通讯作者：
Hasselgren, Per-Olof
中科院分区：
文献类型：
--
作者：
Alamdari, Nima;Aversa, Zaira;Castillero, Estibaliz;Hasselgren, Per-Olof
关键词：
我们回顾了最近的证据，细胞蛋白的乙酰化和去乙酰化，包括转录因子和核辅因子，可能参与肌肉质量的调节。蛋白质乙酰化水平由组蛋白乙酰转移酶(HATS)和组蛋白去乙酰基酶(HDACs)平衡，研究表明，这种平衡在肌肉萎缩中受到干扰。在肌肉萎缩中，转录因子的高乙酰化和调节基因转录的核辅因子可能会影响肌肉质量。此外，超乙酰化可能通过不同的机制使蛋白质容易降解，包括HATS发挥的内在泛素连接酶活性和蛋白质从细胞伴侣中解离。在最近的研究中，抑制p300/HAT的表达和活性以及刺激依赖于SIRT1的HDAC活性可以减少糖皮质激素诱导的骨骼肌分解代谢反应，进一步证明超乙酰化在肌肉萎缩中起作用。然而，应该注意的是，尽管有几项研究提倡超乙酰化在肌肉萎缩中的作用，但显然也有相互矛盾的结果被报道。例如，由失神经或制动引起的肌肉萎缩可能与蛋白质乙酰化减少而不是增加有关。此外，虽然过度乙酰化会导致某些蛋白质的降解增加，但其他蛋白质可能会通过增加乙酰化而稳定下来。因此，乙酰化和去乙酰化在调节肌肉质量中的作用可能是特定于条件和蛋白质的。HATS和HDAC对肌肉质量调节的影响以及调节蛋白质乙酰化的方法是旨在预防和治疗肌肉萎缩的持续研究的重要领域。
We review recent evidence that acetylation and deacetylation of cellular proteins, including transcription factors and nuclear cofactors, may be involved in the regulation of muscle mass. The level of protein acetylation is balanced by histone acetyltransferases (HATs) and histone deacetylases (HDACs) and studies suggest that this balance is perturbed in muscle wasting. Hyperacetylation of transcription factors and nuclear cofactors regulating gene transcription in muscle wasting may influence muscle mass. In addition, hyperacetylation may render proteins susceptible to degradation by different mechanisms, including intrinsic ubiquitin ligase activity exerted by HATs and by dissociation of proteins from cellular chaperones. In recent studies, inhibition of p300/HAT expression and activity and stimulation of SIRT1-dependent HDAC activity reduced glucocorticoid-induced catabolic response in skeletal muscle, providing further evidence that hyperacetylation plays a role in muscle wasting. It should be noted, however, that although several studies advocate a role of hyperacetylation in muscle wasting, apparently contradictory results have also been reported. For example, muscle atrophy caused by denervation or immobilization may be associated with reduced, rather than increased, protein acetylation. In addition, whereas hyperacetylation results in increased degradation of certain proteins, other proteins may be stabilized by increased acetylation. Thus, the role of acetylation and deacetylation in the regulation of muscle mass may be both condition- and protein-specific. The influence of HATs and HDACs on the regulation of muscle mass as well as methods to modulate protein acetylation are important areas for continued research aimed at preventing and treating muscle wasting.
登录
查看更多内容
影响因子：
4.8
作者：
Cohen, Todd J.;Waddell, David S.;Yao, Tso-Pang
通讯作者：
Yao, Tso-Pang
DOI：
10.1152/ajpendo.00530.2010
发表时间：
2011-11-01
影响因子：
5.1
作者：
Centeno-Baez, Carolina;Dallaire, Patrice;Marette, Andre
通讯作者：
Marette, Andre
影响因子：
4.8
作者：
Balasubramanyam, K;Varier, RA;Kundu, TK
通讯作者：
Kundu, TK
影响因子：
8.8
作者：
Callahan LA;Supinski GS
通讯作者：
Supinski GS
影响因子：
16
作者：
Black, Joshua C.;Mosley, Amber;Kitada, Tasuku;Washburn, Michael;Carey, Michael
通讯作者：
Carey, Michael