Molecular mechanism underlying muscle mass retention in hibernating bats: Role of periodic arousal

2010 ◽  
Vol 222 (2) ◽  
pp. 313-319 ◽  
Author(s):  
Kisoo Lee ◽  
Hyekyoung So ◽  
Taesik Gwag ◽  
Hyunwoo Ju ◽  
Ju-Woon Lee ◽  
...  
2018 ◽  
Vol 22 (5) ◽  
pp. 9-16 ◽  
Author(s):  
M. Z. Gasanov

In recent decades, the main pathogenetic mechanisms for maintaining muscle mass and strength have been discovered. Most of the scientific papers on the molecular aspects of the  pathogenesis of sarcopenia were focused on the Akt-signaling  pathway. The subject of the study were people of elderly and senile  age, immobilized patients, patients with CKD 1-4 stages, animals. However, recently more attention has been paid to the role  of protein – the mammalian target of rapamycin mTOR. It seems to be a key link in the control of muscle mass and is a promising  marker in understanding the mechanisms of the pathogenesis of  sarcopenia. Its importance in protein metabolism in patients with  end stage kidney disease is not studied and requires further research. The presented scientific review contains  information on the role of mTOR and its components – mTORC1 and mTORC2 in maintaining muscle mass and strength in a healthy  person and in the formation of sarcopenia in patients with CKD. The  general aid of mTORC1 complex is regulation of protein production  which is necessary for cell growth and differentiation. mTORC2  complex functions are not enough studied. It is established that it  plays important role in such biological processes as cytoskeleton  organization, intracellular homeostasis maintaining, so it provides  cell resistance and cell survivability in negative external and internal  impulses. mTOR protein can be considered as promising molecular  marker in diagnostics of protein metabolism early disturbances in  patients with CKD and also as additory factor of sarcopenia severity assessment.


2020 ◽  
Vol 20 (1) ◽  
pp. 44-54 ◽  
Author(s):  
Sonali Bhakta ◽  
Toshifumi Tsukahara

Editing mutated genes is a potential way for the treatment of genetic diseases. G-to-A mutations are common in mammals and can be treated by adenosine-to-inosine (A-to-I) editing, a type of substitutional RNA editing. The molecular mechanism of A-to-I editing involves the hydrolytic deamination of adenosine to an inosine base; this reaction is mediated by RNA-specific deaminases, adenosine deaminases acting on RNA (ADARs), family protein. Here, we review recent findings regarding the application of ADARs to restoring the genetic code along with different approaches involved in the process of artificial RNA editing by ADAR. We have also addressed comparative studies of various isoforms of ADARs. Therefore, we will try to provide a detailed overview of the artificial RNA editing and the role of ADAR with a focus on the enzymatic site directed A-to-I editing.


2021 ◽  
Vol 22 (6) ◽  
pp. 3032
Author(s):  
Anna Picca ◽  
Riccardo Calvani

Sarcopenia involves a progressive age‐related decline of skeletal muscle mass and strength/function [...]


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Thomas Wilkinson ◽  
Eleanor Gore ◽  
Jared Palmer ◽  
Luke Baker ◽  
Emma Watson ◽  
...  

Abstract Background and Aims Individuals living with CKD are characterised by adverse changes in physical function. Knowledge of the factors that mediate impairments in physical functioning is crucial for developing effective interventions that preserve mobility and future independence. Mechanical muscle power describes the rate of performing work and is the product of muscular force and velocity of contraction. Muscle power has been shown to have stronger associations with functional limitations and mortality than sarcopenia in older adults. In CKD, the role of mechanical muscle power is poorly understood and is overlooked as a target in many rehabilitation programmes, often at the expense of muscle mass or strength. The aims of this study were to 1) explore the prevalence of low absolute mechanical power, low relative mechanical power, and low specific mechanical power in CKD; and 2) investigate the association of mechanical power with the ability to complete activities of daily living and physical performance. Method Mechanical muscle power (relative, allometric, specific) was calculated using the sit-to-stand-5 (STS5) test as per previously validated equations. Legs lean mass was derived from regional analyses conducted using bioelectrical impedance analysis (BIA). Physical performance was assessed using two objective tests: usual gait speed and the ‘time-up-and-go’ (TUAG) test. Self-reported activities of daily living (ADLs) were assessed via the Duke Activity Status Index (DASI). Balance and postural stability (postural sway and velocity) was assessed using a FysioMeter. Sex-specific tertiles were used to determine low, medium and high levels of relative STS power and its main components. Results 102 participants with non-dialysis CKD were included (mean age: 62.0 (±14.1) years, n=49 males (48%), mean eGFR: 38.0 (±21.5) ml.min.1.73m2). The mean estimated relative power was 3.1 (±1.5) W.kg in females and 3.3 (±1.3) W.kg in males. Low relative power was found in 35/102 (34%) patients. Relative power was a significant independent predictor of self-reported ADLs (via the DASI) (B=.413, P=.004), and performance on the TUAG (B=-.719, P<.001) and gait speed (B=.404, P=.003) tests. Skeletal muscle mass was not associated with the DASI or any of the objective function tests Conclusion Patients presenting with low muscle power would benefit from participation in appropriate interventions designed to improve the physiological components accounting for low relative muscle power. Assessment of power can be used to tailor renal rehabilitation programmes as shown in Figure 1. Incorporation of power-based training, a novel type of strength training, designed by manipulating traditional strength training variables and primarily movement velocity and training intensity may present the best strategy for improving physical function in CKD.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Monte Willis ◽  
Rongqin Ren ◽  
Cam Patterson

Bone morphogenetic proteins (BMPs) of the TGF-beta superfamily, have been implicated in multiple processes during cardiac development. Our laboratory recently described an unprecedented role for Bmper in antagonizing BMP-2, BMP-4, and BMP-6. To determine the role of Bmper on cardiac development in vivo, we created Bmper null (Bmper −/−) mice by replacing exons 1 and 2 with GFP. Since Bmper −/− mice are perinatally lethal, we determined pre-natal cardiac function of Bmper −/− mice in utero just before birth. By echocardiography, E18.5 Bmper −/− embryos had decreased cardiac function (24.2 +/− 8.1% fractional shortening) compared to Bmper +/− and Bmper +/+ siblings (52.2 +/− 1.6% fractional shortening) (N=4/group). To further characterize the role of Bmper on cardiac function in adult mice, we performed echocardiography on 8-week old male and female Bmper +/− and littermate control Bmper +/+. Bmper +/− mice had an approximately 15% decrease in anterior and posterior wall thickness compared to sibling Bmper +/+ mice at baseline (n=10/group). Cross-sectional areas of Bmper +/− cardiomyocytes were approximately 20% less than wild type controls, indicating cardiomyocyte hypoplasia in adult Bmper +/− mice at baseline. Histologically, no significant differences were identified in representative H&E and trichrome stained adult Bmper +/− and Bmper +/+ cardiac sections at baseline. To determine the effects of Bmper expression on the development of cardiac hypertrophy, both Bmper +/− and Bmper +/+ sibling controls underwent transaortic constriction (TAC), followed by weekly echocardiography. While a deficit was identified in Bmper +/− mice at baseline, both anterior and posterior wall thicknesses increased after TAC, such that identical wall thicknesses were identified in Bmper +/− and Bmper +/+ mice 1–4 weeks after TAC. Notably, cardiac function (fractional shortening %) and histological evaluation revealed no differences between Bmper +/− and Bmper +/+ any time after TAC. These studies identify for the first time that Bmper expression plays a critical role in regulating cardiac muscle mass during development, and that Bmper regulates the development of hypertrophy in response to pressure overload in vivo.


2006 ◽  
Vol 290 (6) ◽  
pp. C1651-C1659 ◽  
Author(s):  
Brenda A. Bondesen ◽  
Stephen T. Mills ◽  
Grace K. Pavlath

Loss of muscle mass occurs with disease, injury, aging, and inactivity. Restoration of normal muscle mass depends on myofiber growth, the regulation of which is incompletely understood. Cyclooxygenase (COX)-2 is one of two isoforms of COX that catalyzes the synthesis of prostaglandins, paracrine hormones that regulate diverse physiological and pathophysiological processes. Previously, we demonstrated that the COX-2 pathway regulates early stages of myofiber growth during muscle regeneration. However, whether the COX-2 pathway plays a common role in adult myofiber growth or functions specifically during muscle regeneration is unknown. Therefore, we examined the role of COX-2 during myofiber growth following atrophy in mice. Muscle atrophy was induced by hindlimb suspension (HS) for 2 wk, followed by a reloading period, during which mice were treated with either the COX-2-selective inhibitor SC-236 (6 mg·kg−1·day−1) or vehicle. COX-2 protein was expressed and SC-236 attenuated myofiber growth during reloading in both soleus and plantaris muscles. Attenuated myofiber growth in the soleus was associated with both decreased myonuclear addition and decreased inflammation, whereas neither of these processes mediated the effects of SC-236 on plantaris growth. In addition, COX-2−/− satellite cells exhibited impaired activation/proliferation in vitro, suggesting direct regulation of muscle cell activity by COX-2. Together, these data suggest that the COX-2 pathway plays a common regulatory role during various types of muscle growth via multiple mechanisms.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Andrew S McNeal ◽  
Rachel L Belote ◽  
Hanlin Zeng ◽  
Marcus Urquijo ◽  
Kendra Barker ◽  
...  

Benign melanocytic nevi frequently emerge when an acquired BRAFV600E mutation triggers unchecked proliferation and subsequent arrest in melanocytes. Recent observations have challenged the role of oncogene-induced senescence in melanocytic nevus formation, necessitating investigations into alternative mechanisms for the establishment and maintenance of proliferation arrest in nevi. We compared the transcriptomes of melanocytes from healthy human skin, nevi, and melanomas arising from nevi and identified a set of microRNAs as highly expressed nevus-enriched transcripts. Two of these microRNAs—MIR211-5p and MIR328-3p—induced mitotic failure, genome duplication, and proliferation arrest in human melanocytes through convergent targeting of AURKB. We demonstrate that BRAFV600E induces a similar proliferation arrest in primary human melanocytes that is both reversible and conditional. Specifically, BRAFV600E expression stimulates either arrest or proliferation depending on the differentiation state of the melanocyte. We report genome duplication in human melanocytic nevi, reciprocal expression of AURKB and microRNAs in nevi and melanomas, and rescue of arrested human nevus cells with AURKB expression. Taken together, our data describe an alternative molecular mechanism for melanocytic nevus formation that is congruent with both experimental and clinical observations.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yujie Zhang ◽  
Yanyan Wang ◽  
Liwei Ying ◽  
Sifeng Tao ◽  
Mingmin Shi ◽  
...  

Osteosarcoma is the most common primary bone malignancy, typically occurring in childhood or adolescence. Unfortunately, the clinical outcomes of patients with osteosarcoma are usually poor because of the aggressive nature of this disease and few treatment advances in the past four decades. N6-methyladenosine (m6A) is one of the most extensive forms of RNA modification in eukaryotes found both in coding and non-coding RNAs. Accumulating evidence suggests that m6A-related factors are dysregulated in multiple osteosarcoma processes. In this review, we highlight m6A modification implicated in osteosarcoma, describing its pathophysiological role and molecular mechanism, as well as future research trends and potential clinical application in osteosarcoma.


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