Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells

Nakai, Norihiro; Kawano, Fuminori; Nakata, Ken

doi:10.1007/s11010-015-2446-7

Cited by 18 publications

(14 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar paradoxical observations have been described in previous studies ( Ng et al, 2012 ; Nakai et al, 2015 ). In an extracellular matrix detachment model, Ng et al (2012) demonstrated that after detachment AMPK is activated in both K-Ras V12-transformed and non-transformed mouse embryonic fibroblasts; interestingly, mTORC1 activity only decreased, in an AMPK-dependent manner, in transformed but not non-transformed fibroblasts.…”

Section: Discussionsupporting

confidence: 92%

Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration

Zheng

Boyer

Jin

et al. 2016

eLife

121

102

View full text Add to dashboard Cite

mTOR inhibition is beneficial in neurodegenerative disease models and its effects are often attributable to the modulation of autophagy and anti-apoptosis. Here, we report a neglected but important bioenergetic effect of mTOR inhibition in neurons. mTOR inhibition by rapamycin significantly preserves neuronal ATP levels, particularly when oxidative phosphorylation is impaired, such as in neurons treated with mitochondrial inhibitors, or in neurons derived from maternally inherited Leigh syndrome (MILS) patient iPS cells with ATP synthase deficiency. Rapamycin treatment significantly improves the resistance of MILS neurons to glutamate toxicity. Surprisingly, in mitochondrially defective neurons, but not neuroprogenitor cells, ribosomal S6 and S6 kinase phosphorylation increased over time, despite activation of AMPK, which is often linked to mTOR inhibition. A rapamycin-induced decrease in protein synthesis, a major energy-consuming process, may account for its ATP-saving effect. We propose that a mild reduction in protein synthesis may have the potential to treat mitochondria-related neurodegeneration.DOI: http://dx.doi.org/10.7554/eLife.13378.001

show abstract

Section: Discussionsupporting

confidence: 92%

Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration

Zheng

Boyer

Jin

et al. 2016

eLife

121

102

View full text Add to dashboard Cite

show abstract

“…Several cyclic stretching-induced effects have been discussed previously, such as cell proliferation, the disruption of cell-cell communication, and microtubule reorganization [24,[59][60][61]. These biological functions are activated by different signaling pathways [13,60,[62][63][64]. However, the cyclic stretchinginduced global phosphoproteome remains lacking.…”

Section: Discussionmentioning

confidence: 99%

Quantitative Phosphoproteomics Reveals Cell Alignment and Mitochondrial Length Change under Cyclic Stretching in Lung Cells

Wang

Hsu

Huang³

et al. 2020

IJMS

View full text Add to dashboard Cite

Lung cancer is a leading cause of death. Most previous studies have been based on traditional cell-culturing methods. However, lung cells are periodically subjected to mechanical forces during breathing. Understanding the mechanisms underlying the cyclic stretching induced in lung cells may be important for lung cancer therapy. Here, we applied cyclic stretching to stimulate the continual contraction that is present under physiological conditions in lung cells. We first uncovered the stretching-induced phosphoproteome in lung cancer cell line A549 and fibroblast cell line IMR-90. We identified 2048 and 2604 phosphosites corresponding to 837 and 1008 phosphoproteins in A549 and IMR-90, respectively. Furthermore, we combined our phosphoproteomics and public gene expression data to identify the biological functions in response to cyclic stretching. Interestingly, cytoskeletal and mitochondrial reorganization were enriched. We further used cell imaging analysis to validate the profiling results and found that this physical force changed cell alignment and mitochondrial length. This study not only reveals the molecular mechanism of cyclic stretching but also provides evidence that cell stretching causes cellular rearrangement and mitochondrial length change.

show abstract

“…Trolox (Sigma-Aldrich, Italy, 0.1 mM) was used as a positive control for the antioxidant effect as described in Sestili et al [15]. Aminoimidazole-4-carboxamide ribonucleotide (AICAR, Sigma-Aldrich, Italy) was used (2 mM for 1 h) as a positive control for AMPK activation [31]. …”

Section: Methodsmentioning

confidence: 99%

Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity

Barbieri

Guescini

Calcabrini

et al. 2016

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Creatine (Cr) is a nutritional supplement promoting a number of health benefits. Indeed Cr has been shown to be beneficial in disease-induced muscle atrophy, improve rehabilitation, and afford mild antioxidant activity. The beneficial effects are likely to derive from pleiotropic interactions. In accord with this notion, we previously demonstrated that multiple pleiotropic effects, including preservation of mitochondrial damage, account for the capacity of Cr to prevent the differentiation arrest caused by oxidative stress in C2C12 myoblasts. Given the importance of mitochondria in supporting the myogenic process, here we further explored the protective effects of Cr on the structure, function, and networking of these organelles in C2C12 cells differentiating under oxidative stressing conditions; the effects on the energy sensor AMPK, on PGC-1α, which is involved in mitochondrial biogenesis and its downstream effector Tfam were also investigated. Our results indicate that damage to mitochondria is crucial in the differentiation imbalance caused by oxidative stress and that the Cr-prevention of these injuries is invariably associated with the recovery of the normal myogenic capacity. We also found that Cr activates AMPK and induces an upregulation of PGC-1α expression, two events which are likely to contribute to the protection of mitochondrial quality and function.

show abstract

Mechanical stretch activates mammalian target of rapamycin and AMP-activated protein kinase pathways in skeletal muscle cells

Cited by 18 publications

References 48 publications

Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration

Alleviation of neuronal energy deficiency by mTOR inhibition as a treatment for mitochondria-related neurodegeneration

Quantitative Phosphoproteomics Reveals Cell Alignment and Mitochondrial Length Change under Cyclic Stretching in Lung Cells

Creatine Prevents the Structural and Functional Damage to Mitochondria in Myogenic, Oxidatively Stressed C2C12 Cells and Restores Their Differentiation Capacity

Contact Info

Product

Resources

About