Effect of sarcolipin-mediated cell transdifferentiation in sarcopenia-associated skeletal muscle fibrosis

Chen, Qiunan; Fan, Zhen; Lyu, Ankang; Wu, Jing; Guo, Ai; Yang, Yunfei; Chen, Jinliang

doi:10.1016/j.yexcr.2020.111890

Cited by 27 publications

(21 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously, our team found that d -gal could induce C2C12 cell senescence [ 29 ], so we used d -gal to generate a senescent cell model. In this model, we found that MICU3 was decreased [Fig.…”

Section: Resultsmentioning

confidence: 99%

MICU3 regulates mitochondrial Ca2+-dependent antioxidant response in skeletal muscle aging

Yang

Liao

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Age-related loss of skeletal muscle mass and function, termed sarcopenia, could impair the quality of life in the elderly. The mechanisms involved in skeletal muscle aging are intricate and largely unknown. However, more and more evidence demonstrated that mitochondrial dysfunction and apoptosis also play an important role in skeletal muscle aging. Recent studies have shown that mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium affects skeletal muscle mass and function by affecting mitochondrial function. During aging, we observed downregulated expression of mitochondrial calcium uptake family member3 (MICU3) in skeletal muscle, a regulator of MCU, which resulted in a significant reduction in mitochondrial calcium uptake. However, the role of MICU3 in skeletal muscle aging remains poorly understood. Therefore, we investigated the effect of MICU3 on the skeletal muscle of aged mice and senescent C2C12 cells induced by d-gal. Downregulation of MICU3 was associated with decreased myogenesis but increased oxidative stress and apoptosis. Reconstitution of MICU3 enhanced antioxidants, prevented the accumulation of mitochondrial ROS, decreased apoptosis, and increased myogenesis. These findings indicate that MICU3 might promote mitochondrial Ca2+ homeostasis and function, attenuate oxidative stress and apoptosis, and restore skeletal muscle mass and function. Therefore, MICU3 may be a potential therapeutic target in skeletal muscle aging.

show abstract

Section: Resultsmentioning

confidence: 99%

MICU3 regulates mitochondrial Ca2+-dependent antioxidant response in skeletal muscle aging

Yang

Liao

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Conversely, we found that SLN was significantly upregulated in the soleus in response to spaceflight, which again was, to some extent, expected. SLN is a well-established SERCA uncoupler [ 25 , 38 ] that is upregulated in many muscle wasting conditions, including muscular dystrophy [ 39 ], sarcopenia [ 40 ], and soleus unloading [ 34 , 41 ]. SLN has been shown to promote calcineurin signaling via SERCA inhibition, thereby promoting the oxidative phenotype and muscle mass [ 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight

Braun

Geromella

Hamstra

et al. 2021

IJMS

View full text Add to dashboard Cite

It is well established that microgravity exposure causes significant muscle weakness and atrophy via muscle unloading. On Earth, muscle unloading leads to a disproportionate loss in muscle force and size with the loss in muscle force occurring at a faster rate. Although the exact mechanisms are unknown, a role for Ca2+ dysregulation has been suggested. The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump actively brings cytosolic Ca2+ into the SR, eliciting muscle relaxation and maintaining low intracellular Ca2+ ([Ca2+]i). SERCA dysfunction contributes to elevations in [Ca2+]i, leading to cellular damage, and may contribute to the muscle weakness and atrophy observed with spaceflight. Here, we investigated SERCA function, SERCA regulatory protein content, and reactive oxygen/nitrogen species (RONS) protein adduction in murine skeletal muscle after 35–37 days of spaceflight. In male and female soleus muscles, spaceflight led to drastic impairments in Ca2+ uptake despite significant increases in SERCA1a protein content. We attribute this impairment to an increase in RONS production and elevated total protein tyrosine (T) nitration and cysteine (S) nitrosylation. Contrarily, in the tibialis anterior (TA), we observed an enhancement in Ca2+ uptake, which we attribute to a shift towards a faster muscle fiber type (i.e., increased myosin heavy chain IIb and SERCA1a) without elevated total protein T-nitration and S-nitrosylation. Thus, spaceflight affects SERCA function differently between the soleus and TA.

show abstract

“…At present, in the field of ageing and anti‐ageing at home and abroad, the d ‐galactose subacute ageing model, as an ideal mouse model, has been widely used in research on senile diseases, anti‐ageing measures, and anti‐ageing drug screening 100 . Chen et al 101 . used d ‐galactose to induce senescence of C2C12 myoblasts in mice and further concluded that targeted sarcolipin may be a new therapeutic strategy to alleviate muscle fibrosis associated with sarcopenia.…”

Section: Classification Of Mouse Models Of Sarcopeniamentioning

confidence: 99%

Mouse models of sarcopenia: classification and evaluation

Xie

Dong-sheng

et al. 2021

J cachexia sarcopenia muscle

114

View full text Add to dashboard Cite

Sarcopenia is a progressive and widespread skeletal muscle disease that is related to an increased possibility of adverse consequences such as falls, fractures, physical disabilities and death, and its risk increases with age. With the deepening of the understanding of sarcopenia, the disease has become a major clinical disease of the elderly and a key challenge of healthy ageing. However, the exact molecular mechanism of this disease is still unclear, and the selection of treatment strategies and the evaluation of its effect are not the same. Most importantly, the early symptoms of this disease are not obvious and are easy to ignore. In addition, the clinical manifestations of each patient are not exactly the same, which makes it difficult to effectively study the progression of sarcopenia. Therefore, it is necessary to develop and use animal models to understand the pathophysiology of sarcopenia and develop therapeutic strategies. This paper reviews the mouse models that can be used in the study of sarcopenia, including ageing models, genetically engineered models, hindlimb suspension models, chemical induction models, denervation models, and immobilization models; analyses their advantages and disadvantages and application scope; and finally summarizes the evaluation of sarcopenia in mouse models.

show abstract

Effect of sarcolipin-mediated cell transdifferentiation in sarcopenia-associated skeletal muscle fibrosis

Cited by 27 publications

References 29 publications

MICU3 regulates mitochondrial Ca2+-dependent antioxidant response in skeletal muscle aging

MICU3 regulates mitochondrial Ca2+-dependent antioxidant response in skeletal muscle aging

Characterizing SERCA Function in Murine Skeletal Muscles after 35–37 Days of Spaceflight

Mouse models of sarcopenia: classification and evaluation

Contact Info

Product

Resources

About