Hypertrophy of Rat Skeletal Muscle Is Associated with Increased SIRT1/Akt/mTOR/S6 and Suppressed Sestrin2/SIRT3/FOXO1 Levels.
Hypertrophy of Rat Skeletal Muscle Is Associated with Increased SIRT1/Akt/mTOR/S6 and Suppressed Sestrin2/SIRT3/FOXO1 Levels.
复制标题
大鼠骨骼肌肥大与 SIRT1/Akt/mTOR/S6 增加和 Sestrin2/SIRT3/FOXO1 水平抑制相关。
DOI：
10.3390/ijms22147588
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发表时间：
2021-07-15
影响因子：
5.6
通讯作者：
Radak Z
中科院分区：
文献类型：
--
作者：
Gombos Z;Koltai E;Torma F;Bakonyi P;Kolonics A;Aczel D;Ditroi T;Nagy P;Kawamura T;Radak Z
尽管对骨骼肌肥大的分子机制进行了深入的研究，但其潜在的信号传导过程尚未完全了解。因此，我们采用超载模型，通过手术切除足底肌的主要协同肌（腓肠肌、比目鱼肌），使8月龄Wistar雄性大鼠剩余足底肌出现明显超载。研究了sirt1相关的促合成代谢、促分解代谢分子信号通路、NAD和H2S水平。与假手术动物相比，超载14天导致足底肌肉质量显著增加43% （p < 0.01）。胱硫氨酸-β-合成酶（CBS）活性和生物可利用H2S水平不受超载影响。另一方面，过度负荷引起的骨骼肌肥大与SIRT1 （p < 0.01）、Akt （p < 0.01）、mTOR、S6 （p < 0.01）和sestrin 2 （p < 0.01）水平升高有关，这些蛋白主要负责合成代谢信号传导。FOXO1和SIRT3信号减少（p < 0.01）提示蛋白分解和线粒体自噬下调。NAD+、sestrin2、OGG1水平降低（p < 0.01）表明超载14 d后骨骼肌氧化还原环境降低。目前的研究揭示了在骨骼肌肥大中调节合成代谢和分解代谢过程的新的细胞相互作用。
Despite the intensive investigation of the molecular mechanism of skeletal muscle hypertrophy, the underlying signaling processes are not completely understood. Therefore, we used an overload model, in which the main synergist muscles (gastrocnemius, soleus) of the plantaris muscle were surgically removed, to cause a significant overload in the remaining plantaris muscle of 8-month-old Wistar male rats. SIRT1-associated pro-anabolic, pro-catabolic molecular signaling pathways, NAD and H2S levels of this overload-induced hypertrophy were studied. Fourteen days of overload resulted in a significant 43% (p < 0.01) increase in the mass of plantaris muscle compared to sham operated animals. Cystathionine-β-synthase (CBS) activities and bioavailable H2S levels were not modified by overload. On the other hand, overload-induced hypertrophy of skeletal muscle was associated with increased SIRT1 (p < 0.01), Akt (p < 0.01), mTOR, S6 (p < 0.01) and suppressed sestrin 2 levels (p < 0.01), which are mostly responsible for anabolic signaling. Decreased FOXO1 and SIRT3 signaling (p < 0.01) suggest downregulation of protein breakdown and mitophagy. Decreased levels of NAD+, sestrin2, OGG1 (p < 0.01) indicate that the redox milieu of skeletal muscle after 14 days of overloading is reduced. The present investigation revealed novel cellular interactions that regulate anabolic and catabolic processes in the hypertrophy of skeletal muscle.
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影响因子：
4.8
作者：
Lee, Donghoon;Goldberg, Alfred L.
通讯作者：
Goldberg, Alfred L.
影响因子：
16.6
作者：
Kim, Myungjin;Sujkowski, Alyson;Lee, Jun Hee
通讯作者：
Lee, Jun Hee
DOI：
10.1126/science.1182228
发表时间：
2010-03-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lee JH;Budanov AV;Park EJ;Birse R;Kim TE;Perkins GA;Ocorr K;Ellisman MH;Bodmer R;Bier E;Karin M
通讯作者：
Karin M
影响因子：
--
作者：
Ji, Li Li;Yeo, Dongwook
通讯作者：
Yeo, Dongwook
影响因子：
4.6
作者：
Hwang, Hwan-Jin;Kim, Joo Won;Yoo, Hye Jin
通讯作者：
Yoo, Hye Jin