Stretching magnitude–dependent inactivation of AKT by ROS led to enhanced p53 mitochondrial translocation and myoblast apoptosis

Song, Jing; Wang, Yaqi; Yuan, Xiao; Ji, Qiuxia; Fan, Cunzheng; Zhao, Hongmei; Hao, Wenjing

doi:10.1091/mbc.e18-12-0770

Cited by 14 publications

(10 citation statements)

References 81 publications

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“…The myostatin gene activates Smad2 signaling and inhibits Akt activation, thereby altering the expression of multiple genes involved in the regulation of protein degradation and increasing skeletal muscle apoptosis [ 9 , 72 , 73 ]. Previous studies on ROS-related factors inducing myoblast apoptosis have shown that the p53 and Akt pathways are involved in cell apoptosis and ROS accumulation [ 74 , 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury

Chen

Yang

et al. 2020

Molecules

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Glucocorticoids are widely used anti-inflammatory drugs in clinical settings. However, they can induce skeletal muscle atrophy by reducing fiber cross-sectional area and myofibrillar protein content. Studies have proven that antioxidants can improve glucocorticoid-induced skeletal muscle atrophy. Quercetin is a potent antioxidant flavonoid widely distributed in fruits and vegetables and has shown protective effects against dexamethasone-induced skeletal muscle atrophy. In this study, we demonstrated that dexamethasone significantly inhibited cell growth and induced cell apoptosis by stimulating hydroxyl free radical production in C2C12 skeletal muscle cells. Our results evidenced that quercetin increased C2C12 skeletal cell viability and exerted antiapoptotic effects on dexamethasone-treated C2C12 cells by regulating mitochondrial membrane potential (ΔΨm) and reducing oxidative species. Quercetin can protect against dexamethasone-induced muscle atrophy by regulating the Bax/Bcl-2 ratio at the protein level and abnormal ΔΨm, which leads to the suppression of apoptosis.

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Section: Discussionmentioning

confidence: 99%

Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury

Chen

Yang

et al. 2020

Molecules

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“…On the other hand, mitochondrion was another important organelle involving in stretching-induced myoblast death, with mitochondrial maker protein apoptosis-inducing factor (AIF) level being elevated during mechanical stretch [84]. Furthermore, we found a stretching magnitude-dependent increment of reactive oxygen species (ROS) in C2C12 myoblasts, which activated two pathways that contribute to myoblast death: JNK and p53 [85,86]. When ROS was inhibited, stretch-activated JNK was also attenuated; inhibition of both ROS and JNK could alleviate myoblast apoptosis under stretching stimuli [85].…”

Section: Molecular Mechanisms Of Stretch-induced Myoblast Deathmentioning

confidence: 79%

“…When ROS was inhibited, stretch-activated JNK was also attenuated; inhibition of both ROS and JNK could alleviate myoblast apoptosis under stretching stimuli [85]. Furthermore, ROS-induced p53 mitochondrial translocation only occurred when ROS was overaccumulated by stretching stimuli, which was a critical event leading to myoblast apoptosis, possibly depending upon classical mitochondrial apoptotic pathways [86].…”

Section: Molecular Mechanisms Of Stretch-induced Myoblast Deathmentioning

confidence: 97%

“…Notably, some pathways were frequently mentioned in different studies, such as Src [22,38,47,87], NF-jB [22][23][24]26,54,85], p38 [26,31,32,38,45,47,51,52,54,58], FAK [22,49,66], IGF-1 [28][29][30][31][32], NOS [16,21,23,46,66,71], AKT [31,32,40,45,86], and mTOR [38][39][40], in spite of various stretching parameters being used in these studies. To some extent, this suggests these pathways are more mechanosensitive, and are more easily activated during distinct type of mechanical strain.…”

Section: Interconnections Among the Mechanosensitive Pathways In Myobmentioning

confidence: 99%

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Multiple Effects of Mechanical Stretch on Myogenic Progenitor Cells

Wang

Song

Liu

et al. 2020

Stem Cells and Development

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Mechanically stretched skeletal muscle undergoes dramatic shifts in structure, mass, and function. In vitro tensile strain models have demonstrated that myogenic progenitor cells, including satellite cells and myoblasts, are highly mechanosensitive cells, and respond to mechanical strain in a wide variety of aspects. However, the experimental results from different researchers and laboratories are not always in support of each other. Moreover, some specific molecules or signaling pathways were reported to play distinct roles in stretched myogenic cells, according to the statements of different studies. The purpose of this review is to integrate the researches conducting in vitro culture of satellite cells or myoblasts and exploring their mechanoresponses using in vitro stretching apparatus. These responses will be categorized into several groups, such as activation, proliferation, myogenic differentiation, cellular damage or apoptosis, properties of plasma membrane, transdifferentiation, reorientation, etc. In addition, detailed experimental designs like culturing conditions and straining regimens will be displayed and compared, to interpret some contradictory statements in different studies. Furthermore, the currently known interconnections among some mechanosensitive pathways will be pictured to give a better understanding about the complex regulations of myogenic cell responses to mechanical stretch. Hopefully, by summarizing the published studies about mechanoresponses of myogenic progenitor cells, future directions, and perspectives would be made clearer to researchers in this field.

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“…Cyclic mechanical stretch is a known inducer of the up-regulated level of reactive oxygen species (ROS) [4,5]. ROS, as intracellular signaling molecules, can be essential for regulation of cell physiological functions, while excessive accumulation of ROS can disrupt physiological functions and cause numerous pathophysiological processes [6].…”

Section: Introductionmentioning

confidence: 99%

N-acetylcysteine promotes osteogenic differentiation in periodontal ligament stem cells under cyclic mechanical stretch

Zhao

et al. 2021

Preprint

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Background Biomechanical forces are vital for the regulation of skeletal tissue. Mechanical stretch plays a vital role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) during orthodontic treatment. Cyclic mechanical stretch may trigger the up-regulated production of reactive oxygen species (ROS). ROS has a critical effect on bone cell function and the pathophysiology of bone diseases. N-acetylcysteine (NAC), a ROS scavenger, possesses powerful antioxidant capacity. The aim of this study was to determine the role of ROS and NAC in PDLSCs during osteogenic differentiation under cyclic mechanical stretch. We further investigated that the therapeutic potential of NAC to improve the changes of the microstructure of alveolar bone during orthodontic tooth movement in rats by micro-CT system. Methods The expression of COL1 (collagen type I), RUNX2 (runt-related transcription factor 2) and OPN (osteopontin) by qRT-PCR and Western blot experiments, and alkaline phosphatase (ALP) staining as well as ALP activity tests were used to examine osteogenic differentiation tendency of PDLSCs subjected to cyclic mechanical stretch of 10% and 0.5Hz deformation induced by the Flexcell tension system. ROS production in PDLSCs were measured under cyclic mechanical stretch by Flow Cytometry. The levels of reduced glutathione (GSH), oxidized GSH (GSSG) and the GSH/GSSG ratio with or without NAC treatment were analyzed. And we evaluated the changes of the microstructure of alveolar bone during orthodontic tooth movement in rats employing micro-CT system. Results NAC treatment could promote the osteogenic differentiation of PDLSCs under cyclic mechanical stretch. Down-regulated ROS generation and the up-regulated level of GSH and the ratio of GSH/GSSG in PDLSCs treated with NAC were observed in response to cyclic mechanical stretch. NAC improved the microstructure of alveolar bone, including BV/TV (bone volume/total volume), Tb.Th (trabecular thickness), Tb.Sp (trabecular separation) and SMI (microstructure model index), during orthodontic tooth movement in rats. Conclusion These results revealed that NAC might be a potential therapeutic approach for the remodeling of the alveolar bone during orthodontic tooth movement.

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Stretching magnitude–dependent inactivation of AKT by ROS led to enhanced p53 mitochondrial translocation and myoblast apoptosis

Cited by 14 publications

References 81 publications

Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury

Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury

Multiple Effects of Mechanical Stretch on Myogenic Progenitor Cells

N-acetylcysteine promotes osteogenic differentiation in periodontal ligament stem cells under cyclic mechanical stretch

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