scholarly journals Effects of slow-release urea and rumen-protected methionine and histidine on mammalian target of rapamycin (mTOR) signaling and ubiquitin proteasome-related gene expression in skeletal muscle of dairy cows

2016 ◽  
Vol 99 (8) ◽  
pp. 6702-6713 ◽  
Author(s):  
H. Sadri ◽  
F. Giallongo ◽  
A.N. Hristov ◽  
J. Werner ◽  
C.H. Lang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Dairy Cows ◽  
Slow Release ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
Related Gene ◽  
Ubiquitin Proteasome ◽  
Slow Release Urea

scholarly journals The Role of Diacylglycerol Kinase ζ and Phosphatidic Acid in the Mechanical Activation of Mammalian Target of Rapamycin (mTOR) Signaling and Skeletal Muscle Hypertrophy

2013 ◽  
Vol 289 (3) ◽  
pp. 1551-1563 ◽  
Author(s):  
Jae-Sung You ◽  
Hannah C. Lincoln ◽  
Chan-Ran Kim ◽  
John W. Frey ◽  
Craig A. Goodman ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Phosphatidic Acid ◽  
Mechanical Activation ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
Mechanical Stimuli ◽  
Knock Out

The activation of mTOR signaling is essential for mechanically induced changes in skeletal muscle mass, and previous studies have suggested that mechanical stimuli activate mTOR (mammalian target of rapamycin) signaling through a phospholipase D (PLD)-dependent increase in the concentration of phosphatidic acid (PA). Consistent with this conclusion, we obtained evidence which further suggests that mechanical stimuli utilize PA as a direct upstream activator of mTOR signaling. Unexpectedly though, we found that the activation of PLD is not necessary for the mechanically induced increases in PA or mTOR signaling. Motivated by this observation, we performed experiments that were aimed at identifying the enzyme(s) that promotes the increase in PA. These experiments revealed that mechanical stimulation increases the concentration of diacylglycerol (DAG) and the activity of DAG kinases (DGKs) in membranous structures. Furthermore, using knock-out mice, we determined that the ζ isoform of DGK (DGKζ) is necessary for the mechanically induced increase in PA. We also determined that DGKζ significantly contributes to the mechanical activation of mTOR signaling, and this is likely driven by an enhanced binding of PA to mTOR. Last, we found that the overexpression of DGKζ is sufficient to induce muscle fiber hypertrophy through an mTOR-dependent mechanism, and this event requires DGKζ kinase activity (i.e. the synthesis of PA). Combined, these results indicate that DGKζ, but not PLD, plays an important role in mechanically induced increases in PA and mTOR signaling. Furthermore, this study suggests that DGKζ could be a fundamental component of the mechanism(s) through which mechanical stimuli regulate skeletal muscle mass.

scholarly journals Down-Regulation of Akt/Mammalian Target of Rapamycin Signaling Pathway in Response to Myostatin Overexpression in Skeletal Muscle

Endocrinology ◽  
2008 ◽  
Vol 150 (1) ◽  
pp. 286-294 ◽  
Author(s):  
Adel Amirouche ◽  
Anne-Cécile Durieux ◽  
Sébastien Banzet ◽  
Nathalie Koulmann ◽  
Régis Bonnefoy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Muscle Mass ◽  
Protein Metabolism ◽  
Skeletal Muscle Mass ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
Gene Electrotransfer ◽  
Mtor Signaling Pathway

Myostatin, a member of the TGF-β family, has been identified as a master regulator of embryonic myogenesis and early postnatal skeletal muscle growth. However, cumulative evidence also suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression and that myostatin may contribute to muscle mass loss in adulthood. Two major branches of the Akt pathway are relevant for the regulation of skeletal muscle mass, the Akt/mammalian target of rapamycin (mTOR) pathway, which controls protein synthesis, and the Akt/forkhead box O (FOXO) pathway, which controls protein degradation. Here, we provide further insights into the mechanisms by which myostatin regulates skeletal muscle mass by showing that myostatin negatively regulates Akt/mTOR signaling pathway. Electrotransfer of a myostatin expression vector into the tibialis anterior muscle of Sprague Dawley male rats increased myostatin protein level and decreased skeletal muscle mass 7 d after gene electrotransfer. Using RT-PCR and immunoblot analyses, we showed that myostatin overexpression was ineffective to alter the ubiquitin-proteasome pathway. By contrast, myostatin acted as a negative regulator of Akt/mTOR pathway. This was supported by data showing that the phosphorylation of Akt on Thr308, tuberous sclerosis complex 2 on Thr1462, ribosomal protein S6 on Ser235/236, and 4E-BP1 on Thr37/46 was attenuated 7 d after myostatin gene electrotransfer. The data support the conclusion that Akt/mTOR signaling is a key target that accounts for myostatin function during muscle atrophy, uncovering a novel role for myostatin in protein metabolism and more specifically in the regulation of translation in skeletal muscle. Myostatin down-regulates Akt/mammalian target of rapamycin (mTOR) signaling pathway uncovering a novel role for myostatin in protein metabolism and more specifically in the regulation of translation in skeletal muscle.

Sign in / Sign up

Export Citation Format

Share Document