Role of Protein Arginine Methyltransferases and Inflammation in Muscle Pathophysiology

Arginine methylation mediated by protein arginine methyltransferases (PRMTs) is a post-translational modification of both histone and non-histone substrates related to diverse biological processes. PRMTs appear to be critical regulators in skeletal muscle physiology, including regeneration, metabolic homeostasis, and plasticity. Chronic inflammation is commonly associated with the decline of skeletal muscle mass and strength related to aging or chronic diseases, defined as sarcopenia. In turn, declined skeletal muscle mass and strength can exacerbate chronic inflammation. Thus, understanding the molecular regulatory pathway underlying the crosstalk between skeletal muscle function and inflammation might be essential for the intervention of muscle pathophysiology. In this review, we will address the current knowledge on the role of PRMTs in skeletal muscle physiology and pathophysiology with a specific emphasis on its relationship with inflammation.

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Faculty Opinions recommendation of Role of mTORC1 in mechanically induced increases in translation and skeletal muscle mass.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734916606.793571147 ◽

2020 ◽

Author(s):

Stuart M Phillips

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass

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Are STATS Arginine-methylated?

Journal of Biological Chemistry ◽

10.1074/jbc.c400606200 ◽

2005 ◽

Vol 280 (23) ◽

pp. 21700-21705 ◽

Cited By ~ 52

Author(s):

Waraporn Komyod ◽

Uta-Maria Bauer ◽

Peter C. Heinrich ◽

Serge Haan ◽

Iris Behrmann

Keyword(s):

Arginine Methylation ◽

Signaling Cascades ◽

Post Translational Modification ◽

Protein Arginine Methyltransferases ◽

Stat Proteins ◽

Fibrosarcoma Cells ◽

Catalytically Active ◽

Interferon Resistance ◽

Stat Pathway

Transcription factors of the STAT (signal transducer and activator of transcription) family are important in signal transduction of cytokines. They are subject to post-translational modification by phosphorylation on tyrosine and serine residues. Recent evidence suggested that STATs are methylated on a conserved arginine residue within the N-terminal region. STAT arginine methylation has been described to be important for STAT function and loss of arginine methylation was discussed to be involved in interferon resistance of cancer cells. Here we provide several independent lines of evidence indicating that the issue of arginine methylation of STATs has to be reassessed. First, we show that treatment of melanoma and fibrosarcoma cells with inhibitors used to suppress methylation (N-methyl-2-deoxyadenosine, adenosine, dl-homocysteine) had profound and rapid effects on phosphorylation of STAT1 and STAT3 but also on p38 and Erk signaling cascades which are known to cross-talk with the Jak/STAT pathway. Second, we show that anti-methylarginine antibodies did not precipitate specifically STAT1 or STAT3. Third, we show that mutation of Arg31 to Lys led to destabilization of STAT1 and STAT3, implicating an important structural role of Arg31. Finally, purified catalytically active protein arginine methyltransferases (PRMT1, -2, -3, -4, and -6) did not methylate STAT proteins, and cotransfection with PRMT1 did not affect STAT1-controlled reporter gene activity. Taken together, our data suggest the absence of arginine methylation of STAT1 and STAT3.

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Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

International Journal of Molecular Sciences ◽

10.3390/ijms21051628 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1628 ◽

Cited By ~ 3

Author(s):

Keisuke Hitachi ◽

Masashi Nakatani ◽

Shiori Funasaki ◽

Ikumi Hijikata ◽

Mizuki Maekawa ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Muscle Atrophy ◽

Skeletal Muscle Mass ◽

Muscle Size ◽

Skeletal Muscle Atrophy ◽

Myostatin Gene ◽

Expression Levels ◽

Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

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Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake

Aging Cell ◽

10.1111/acel.12342 ◽

2015 ◽

Vol 14 (4) ◽

pp. 511-523 ◽

Cited By ~ 111

Author(s):

Adam P. Sharples ◽

David C. Hughes ◽

Colleen S. Deane ◽

Amarjit Saini ◽

Colin Selman ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Mass ◽

Dietary Restriction ◽

Protein Intake ◽

Skeletal Muscle Mass

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Impact of Sarcopenia as a Prognostic Biomarker of Bladder Cancer

10.20944/preprints201808.0077.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Hiroshi Fukushima ◽

Kosuke Takemura ◽

Hiroaki Suzuki ◽

Fumitaka Koga

Keyword(s):

Skeletal Muscle ◽

Bladder Cancer ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Prognostic Biomarker ◽

Inflammatory Diseases ◽

Poor Nutritional Status ◽

Lack Of Exercise ◽

Worse Prognosis

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.

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