The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy

Cui, Can; Han, Shunshun; Tang, Shuyue; He, Haorong; Shen, Xiaoxu; Zhao, Jing; Chen, Yuqi; Wei, Yuanhang; Wang, Yan; Zhu, Qing; Li, Diyan; Yin, And Huadong

doi:10.3390/ijms21030749

Cited by 33 publications

(30 citation statements)

References 47 publications

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“…Autophagy plays an important role in the process of spinal muscular atrophy and denervated muscle atrophy. Autophagy inhibition can effectively relieve muscle atrophy, and autophagy is a key target for the treatment of muscle atrophy (Piras et al, 2017;Cicardi et al, 2019;Wang et al, 2019;Cui et al, 2020). Our findings demonstrate that isoquercitrin can significantly inhibit mitophagy caused by denervation of the target muscle, accompanied by decreased expression of the autophagy-related proteins ATG7, BNIP3, and PINK1.…”

Section: Discussionmentioning

confidence: 65%

Isoquercitrin Delays Denervated Soleus Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation

et al. 2020

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Although denervated muscle atrophy is common, the underlying molecular mechanism remains unelucidated. We have previously found that oxidative stress and inflammatory response may be early events that trigger denervated muscle atrophy. Isoquercitrin is a biologically active flavonoid with antioxidative and anti-inflammatory properties. The present study investigated the effect of isoquercitrin on denervated soleus muscle atrophy and its possible molecular mechanisms. We found that isoquercitrin was effective in alleviating soleus muscle mass loss following denervation in a dose-dependent manner. Isoquercitrin demonstrated the optimal protective effect at 20 mg/kg/d, which was the dose used in subsequent experiments. To further explore the protective effect of isoquercitrin on denervated soleus muscle atrophy, we analyzed muscle proteolysis via the ubiquitinproteasome pathway, mitophagy, and muscle fiber type conversion. Isoquercitrin significantly inhibited the denervation-induced overexpression of two muscle-specific ubiquitin ligases-muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx), and reduced the degradation of myosin heavy chains (MyHCs) in the target muscle. Following isoquercitrin treatment, mitochondrial vacuolation and autophagy were inhibited, as evidenced by reduced level of autophagy-related proteins (ATG7, BNIP3, LC3B, and PINK1); slow-to-fast fiber type conversion in the target muscle was delayed via triggering expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α); and the production of reactive oxygen species (ROS) in the target muscle was reduced, which might be associated with the upregulation of antioxidant factors (SOD1, SOD2, NRF2, NQO1, and HO1) and the downregulation of ROS production-related factors (Nox2, Nox4, and DUOX1). Furthermore, isoquercitrin treatment reduced the levels of inflammatory factors-interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α)-in the target muscle and inactivated the JAK/STAT3 signaling pathway. Overall, isoquercitrin may alleviate soleus muscle atrophy and mitophagy and reverse the slow-to-fast fiber type conversion following denervation via inhibition of oxidative stress and inflammatory response. Our study findings enrich the knowledge regarding the molecular regulatory mechanisms of denervated muscle atrophy and provide a scientific basis for isoquercitrin as a protective drug for the prevention and treatment of denervated muscle atrophy.

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Section: Discussionmentioning

confidence: 65%

Isoquercitrin Delays Denervated Soleus Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation

et al. 2020

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“…Mutations in these proteins have been linked to various muscle-related disorders and heart diseases 35 . CSRP3 is an autophagy-regulating protein essential for degrading muscle-related components and maintaining muscle structure and function 36 . TCAP is a giant elastic protein with kinase activity that extends half the length of a sarcomere and maintains cellular structure 37 .…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics analysis for the identification of potential age-related genes and cells associated with three major urogenital cancers

Cao

Yang

et al. 2021

Sci Rep

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Age is one of the most important risk factors of the occurrence for tumor patients. The majority of patients with urogenital cancers are the elderly, whose clinical characteristics are greatly affected by age and ageing. Our study aimed to explore age-related genes, cells, and biological changes in three common urogenital cancers via integrative bioinformatics analysis. First, mRNA (count format) and clinical data for bladder cancer, prostate cancer and renal cell carcinoma were downloaded from the Cancer Genome Atlas (TCGA). Through the comparison of clinicopathological characteristics, genes expression and cells infiltration between the old group and the young group, it was found that the clinical characteristics, genes and cells in the tumor microenvironment of different ages were quite different. And 4 key cells, 14 hub genes and some potential pathways were identified and considered as important factors. More importantly, we analyzed the differential landscape of the genes and cells from different perspectives, and confirmed its importance. In conclusion, we identified genes and cell types associated with age-related changes in the tumour microenvironment in urogenital cancer patients. These genes and cell types may play a critical role in the age-associated differences in clinicopathological characteristics among urogenital cancers, thus providing a link between ageing and cancer occurrence. The findings of this study may pave the way for the development of age-tailored approaches to treat cancer and other age-related diseases.

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“…Of note, MLP expression levels have been found increased in muscles from mouse models and human patients affected by different types of myopathies [ 192 , 193 , 194 ]. Recently, MLP has been also involved in promoting autophagosome formation by interacting with LC3, protecting myocytes from apoptosis [ 195 ]. MLP localizes at costameres, where it interacts with zyxin [ 196 ], β1-spectrin [ 197 ] and ILK [ 198 ].…”

Section: Master Regulators Of Muscle Atrophymentioning

confidence: 99%

Master Regulators of Muscle Atrophy: Role of Costamere Components

Gorza

Sorge

Seclì

et al. 2021

Cells

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The loss of muscle mass and force characterizes muscle atrophy in several different conditions, which share the expression of atrogenes and the activation of their transcriptional regulators. However, attempts to antagonize muscle atrophy development in different experimental contexts by targeting contributors to the atrogene pathway showed partial effects in most cases. Other master regulators might independently contribute to muscle atrophy, as suggested by our recent evidence about the co-requirement of the muscle-specific chaperone protein melusin to inhibit unloading muscle atrophy development. Furthermore, melusin and other muscle mass regulators, such as nNOS, belong to costameres, the macromolecular complexes that connect sarcolemma to myofibrils and to the extracellular matrix, in correspondence with specific sarcomeric sites. Costameres sense a mechanical load and transduce it both as lateral force and biochemical signals. Recent evidence further broadens this classic view, by revealing the crucial participation of costameres in a sarcolemmal “signaling hub” integrating mechanical and humoral stimuli, where mechanical signals are coupled with insulin and/or insulin-like growth factor stimulation to regulate muscle mass. Therefore, this review aims to enucleate available evidence concerning the early involvement of costamere components and additional putative master regulators in the development of major types of muscle atrophy.

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The Autophagy Regulatory Molecule CSRP3 Interacts with LC3 and Protects Against Muscular Dystrophy

Cited by 33 publications

References 47 publications

Isoquercitrin Delays Denervated Soleus Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation

Isoquercitrin Delays Denervated Soleus Muscle Atrophy by Inhibiting Oxidative Stress and Inflammation

Transcriptomics analysis for the identification of potential age-related genes and cells associated with three major urogenital cancers

Master Regulators of Muscle Atrophy: Role of Costamere Components

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