Transforming growth factor type beta (TGF-β) requires reactive oxygen species to induce skeletal muscle atrophy

2016 ◽  
Vol 28 (5) ◽  
pp. 366-376 ◽  
Author(s):  
Johanna Abrigo ◽  
Juan Carlos Rivera ◽  
Felipe Simon ◽  
Daniel Cabrera ◽  
Claudio Cabello-Verrugio
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Atrophy ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Skeletal Muscle Atrophy ◽  
Oxygen Species ◽  
Factor Type

scholarly journals Angiotensin-(1-7) Prevents Skeletal Muscle Atrophy Induced by Transforming Growth Factor Type Beta (TGF-β) via Mas Receptor Activation

2016 ◽  
Vol 40 (1-2) ◽  
pp. 27-38 ◽  
Author(s):  
Johanna Ábrigo ◽  
Felipe Simon ◽  
Daniel Cabrera ◽  
Claudio Cabello-Verrugio
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Western Blot ◽  
Muscle Atrophy ◽  
Transforming Growth Factor ◽  
Fibre Diameter ◽  
Skeletal Muscle Atrophy ◽  
Mas Receptor ◽  
Factor Type ◽  
Tgf Β1

Background: Transforming growth factor type beta 1 (TGF-β1) produces skeletal muscle atrophy. Angiotensin-(1-7) (Ang-(1-7)), through the Mas receptor, prevents the skeletal muscle atrophy induced by sepsis, immobilization, or angiotensin II (Ang-II). However, the effect of Ang-(1-7) on muscle wasting induced by TGF-β1 is unknown. Aim: To evaluate whether Ang-(1-7)/Mas receptor axis could prevent the skeletal muscle atrophy induced by TGF-β1. Methods: This study assessed the atrophic effect of TGF-β1 in C2C12 myotubes and mice in absence or presence of Ang-(1-7), and the receptor participation using A779, an antagonist of the Mas receptor. The levels of myosin heavy chain (MHC), polyubiquitination, and MuRF-1 were detected by western blot. Myotube diameter was also evaluated. In vivo analysis included the muscle strength, fibre diameter, MHC and MuRF-1 levels by western blot, and ROS levels by DCF probe detection. Results: The results showed that Ang-(1-7) prevented the increase in MuRF-1 and polyubiquitined protein levels, the decrease of MHC levels, the myotubes/fibre diameter diminution, and the increased production of reactive oxygen species (ROS) induced by TGF-β1. Utilizing A779 inhibited the anti-atrophic effect of Ang-(1-7). Conclusion: The preventive effect of Ang-(1-7) on skeletal muscle atrophy induced by TGF-β1 is produced through inhibition of ROS production and proteasomal degradation of MHC.

TGF-β requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy

2018 ◽  
Vol 399 (3) ◽  
pp. 253-264 ◽  
Author(s):  
Johanna Ábrigo ◽  
Fabian Campos ◽  
Felipe Simon ◽  
Claudia Riedel ◽  
Daniel Cabrera ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Transforming Growth Factor ◽  
Skeletal Muscle Atrophy ◽  
Signalling Pathways ◽  
Oxygen Species ◽  
Mapk Signalling ◽  
Canonical Pathways ◽  
Factor Type ◽  
The Impact

AbstractThe transforming growth factor type-beta (TGF-β) induces skeletal muscle atrophy characterised by a decrease in the fibre’s diameter and levels of myosin heavy chain (MHC), also as an increase of MuRF-1 expression. In addition, TGF-β induces muscle atrophy by a mechanism dependent on reactive oxygen species (ROS). TGF-β signals by activating both canonical Smad-dependent, and non-canonical signalling pathways such as ERK1/2, JNK1/2, and p38 MAPKs. However, the participation of canonical and non-canonical signalling pathways in the TGF-β atrophic effect on skeletal muscle is unknown. We evaluate the impact of Smad and MAPK signalling pathways on the TGF-β-induced atrophic effect in C2C12myotubes. The results indicate that TGF-β activates Smad2/3, ERK1/2 and JNK1/2, but not p38 in myotubes. The pharmacological inhibition of Smad3, ERK1/2 and JNK1/2 activation completely abolished the atrophic effect of TGF-β. Finally, the inhibition of these canonical and non-canonical pathways did not decrease the ROS increment, while the inhibition of ROS production entirely abolished the phosphorylation of Smad3, ERK1/2 and JNK1/2. These results suggest that TGF-β requires Smad3, ERK1/2 and JNK1/2 activation to produce skeletal muscle atrophy. Moreover, the induction of ROS by TGF-β is an upstream event to canonical and non-canonical pathways.

scholarly journals Mitochondrial Reactive Oxygen Species Mediate GPCR–induced TACE/ADAM17-dependent Transforming Growth Factor-α Shedding

2009 ◽  
Vol 20 (24) ◽  
pp. 5236-5249 ◽  
Author(s):  
Timothy J. Myers ◽  
Leann H. Brennaman ◽  
Mary Stevenson ◽  
Shigeki Higashiyama ◽  
William E. Russell ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Transforming Growth Factor Α ◽  
Egfr Activation ◽  
Mitochondrial Ros ◽  
Factor Α

Epidermal growth factor receptor (EGFR) activation by GPCRs regulates many important biological processes. ADAM metalloprotease activity has been implicated as a key step in transactivation, yet the regulatory mechanisms are not fully understood. Here, we investigate the regulation of transforming growth factor-α (TGF-α) shedding by reactive oxygen species (ROS) through the ATP-dependent activation of the P2Y family of GPCRs. We report that ATP stimulates TGF-α proteolysis with concomitant EGFR activation and that this process requires TACE/ADAM17 activity in both murine fibroblasts and CHO cells. ATP-induced TGF-α shedding required calcium and was independent of Src family kinases and PKC and MAPK signaling. Moreover, ATP-induced TGF-α shedding was completely inhibited by scavengers of ROS, whereas calcium-stimulated shedding was partially inhibited by ROS scavenging. Hydrogen peroxide restored TGF-α shedding after calcium chelation. Importantly, we also found that ATP-induced shedding was independent of the cytoplasmic NADPH oxidase complex. Instead, mitochondrial ROS production increased in response to ATP and mitochondrial oxidative complex activity was required to activate TACE-dependent shedding. These results reveal an essential role for mitochondrial ROS in regulating GPCR-induced growth factor shedding.

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