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muscle protein degradation

Stephen Brimijoin, Yang Gao, Liyi Geng, Vicky P Chen
Butyrylcholinesterase (BChE), a plasma enzyme that hydrolyses the neurotransmitter, acetylcholine relatively well, with far lower efficiency than acetylcholinesterase (AChE) but with the capability to degrade a broad range of bioactive esters. AChE is universally understood as essential to cholinergic neurotransmission, voluntary muscle performance, and cognition, among other roles, and its catalytic impact is essential for life. A total absence of BChE activity, whether by enzyme inhibition or simple lack of enzyme protein is not only compatible with life, but does not lead to obvious physiologic disturbance...
2018: Frontiers in Pharmacology
Roger Fielding, Linda Riede, James P Lugo, Aouatef Bellamine
Given its pivotal role in fatty acid oxidation and energy metabolism, l-carnitine has been investigated as ergogenic aid for enhancing exercise capacity in the healthy athletic population. Early research indicates its beneficial effects on acute physical performance, such as increased maximum oxygen consumption and higher power output. Later studies point to the positive impact of dietary supplementation with l-carnitine on the recovery process after exercise. It is demonstrated that l-carnitine alleviates muscle injury and reduces markers of cellular damage and free radical formation accompanied by attenuation of muscle soreness...
March 13, 2018: Nutrients
Takeshi Imamura, Takashi Kaito
BMP(bone morphogenetic protein)and TGF-β(transforming growth factor-β)form a family and play an important role from formation of bone, cartilage and skeletal muscle to their homeostasis. BMP and TGF-β transduce their signals through the cell surface type Ⅰ and type Ⅱ serine/threonine kinase receptors and the intracellular Smad proteins. Several factors regulate BMP and TGF-β signals including activation mechanisms and antagonist outside the cell, co-receptor in the cell membrane, and dephosphorylation by phosphatase and modification/degradation by the ubiquitin-proteasome system in the cell...
2018: Clinical Calcium
A Zissler, B Ehrenfellner, E E Foditsch, F C Monticelli, S Pittner
An accurate estimation of the postmortem interval (PMI) is a central aspect in forensic routine. Recently, a novel approach based on the analysis of postmortem muscle protein degradation has been proposed. However, a number of questions remain to be answered until sensible application of this method to a broad variety of forensic cases is possible. To evaluate whether altered in vivo protein metabolism interferes with postmortem degradation patterns, we conducted a comparative study. We developed a standardized animal degradation model in rats, and collected additional muscle samples from animals recovering from muscle injury and from rats with developed disuse muscle atrophy after induced spinal cord injury...
March 2, 2018: International Journal of Legal Medicine
Ilaria Bellezza, Ileana Giambanco, Alba Minelli, Rosario Donato
Nrf2 and its endogenous inhibitor, Keap1, function as a ubiquitous, evolutionarily conserved intracellular defense mechanism to counteract oxidative stress. Sequestered by cytoplasmic Keap1 and targeted to proteasomal degradation in basal conditions, in case of oxidative stress Nrf2 detaches from Keap1 and translocates to the nucleus, where it heterodimerizes with one of the small Maf proteins. The heterodimers recognize the AREs, that are enhancer sequences present in the regulatory regions of Nrf2 target genes, essential for the recruitment of key factors for transcription...
February 27, 2018: Biochimica et Biophysica Acta
Anas Alzahrani, Yoon Chi, Kenneth W Finnson, Meryem Blati, Bertrand Lussier, Mohit Kapoor, Stephane Roy, Anie Philip
Transforming growth factor (TGF)-β is a multifunctional growth factor with potent pro-fibrotic effects. Endoglin is a TGF-β co-receptor that strongly regulates TGF-β signaling in a variety of cell types. Although aberrant regulation of TGF-β signaling is known to play a key role in fibrotic diseases such as scleroderma and impaired cartilage repair, the significance of endoglin function in regulating these processes is poorly understood. Here we examined whether endoglin haploinsufficiency regulates extracellular (ECM) protein expression and fibrotic responses during bleomycin induced skin fibrosis and surgically induced osteoarthritis, using endoglin-heterozygous (Eng+/-) mice and wild-type (Eng+/+) littermates...
March 2018: Journal of Cell Communication and Signaling
Tomoyasu Kadoguchi, Shingo Takada, Takashi Yokota, Takaaki Furihata, Junichi Matsumoto, Masaya Tsuda, Wataru Mizushima, Arata Fukushima, Koichi Okita, Shintaro Kinugawa
Skeletal muscle atrophy is induced by an imbalance between protein synthesis and degradation. Our previous studies reported that angiotensin II (AII) directly induced muscle atrophy in mice. This study investigated the role of NAD(P)H oxidase 2 (Nox2) activation by AII in the induction of skeletal muscle atrophy. For 4 weeks, either saline (vehicle: V) or AII (1000 ng kg-1  min-1 ) was infused into male wild-type (WT) and Nox2 knockout (KO) mice via osmotic minipumps. Experiments were performed in the following 4 groups: WT + V, KO + V, WT + AII, and KO + AII...
2018: BioMed Research International
Anand Prakash Singh, Swati Sharma, Kirti Pagarware, Rafay Anwar Siraji, Imran Ansari, Anupam Mandal, Pangertoshi Walling, Saima Aijaz
Enteropathogenic E. coli infection is characterized by rapid onset of diarrhea but the underlying mechanisms are not well defined. EPEC targets the tight junctions which selectively regulate the permeability of charged and uncharged molecules. Cooperative actions of the EPEC effectors EspF and Map have been reported to mediate tight junction disruption. To analyze the individual contributions of EspF and Map, we generated in vitro models where EspF and Map, derived from the EPEC strain E2348/69, were constitutively expressed in epithelial cells...
February 27, 2018: Scientific Reports
Mahendran Chinnappan, Aradhana Mohan, Stuti Agarwal, Pranjali Dalvi, Navneet K Dhillon
BACKGROUND: Earlier, we reported that the simultaneous exposure of pulmonary arterial smooth muscle cells to HIV proteins and cocaine results in the attenuation of antiproliferative bone morphogenetic protein receptor-2 (BMPR2) protein expression without any decrease in its mRNA levels. Therefore, in this study, we aimed to investigate the micro RNA-mediated posttranscriptional regulation of BMPR2 expression. METHODS AND RESULTS: We identified a network of BMPR2 targeting micro RNAs including miR-216a to be upregulated in response to cocaine and Tat-mediated augmentation of oxidative stress and transforming growth factor-β signaling in human pulmonary arterial smooth muscle cells...
February 25, 2018: Journal of the American Heart Association
Andrew P Lieberman
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles. The disease is caused by the expansion of a CAG/glutamine tract in the amino-terminus of the androgen receptor. That SBMA exclusively affects males reflects the fact that critical pathogenic events are hormone-dependent. These include translocation of the polyglutamine androgen receptor from the cytoplasm to the nucleus and unfolding of the mutant protein...
2018: Handbook of Clinical Neurology
E A Radugina, E A C Almeida, E Blaber, V A Poplinskaya, Y V Markitantova, E N Grigoryan
Mechanical unloading in microgravity during spaceflight is known to cause muscular atrophy, changes in muscle fiber composition, gene expression, and reduction in regenerative muscle growth. Although some limited data exists for long-term effects of microgravity in human muscle, these processes have mostly been studied in rodents for short periods of time. Here we report on how long-term (30-day long) mechanical unloading in microgravity affects murine muscles of the femoral Quadriceps group. To conduct these studies we used muscle tissue from 6 microgravity mice, in comparison to habitat (7), and vivarium (14) ground control mice from the NASA Biospecimen Sharing Program conducted in collaboration with the Institute for Biomedical Problems of the Russian Academy of Sciences, during the Russian Bion M1 biosatellite mission in 2013...
February 2018: Life Sciences in Space Research
Hamish McGorm, Llion A Roberts, Jeff S Coombes, Jonathan M Peake
Historically, heat has been used in various clinical and sports rehabilitation settings to treat soft tissue injuries. More recently, interest has emerged in using heat to pre-condition muscle against injury. The aim of this narrative review was to collate information on different types of heat therapy, explain the physiological rationale for heat therapy, and to summarise and evaluate the effects of heat therapy before, during and after muscle injury, immobilisation and strength training. Studies on skeletal muscle cells demonstrate that heat attenuates cellular damage and protein degradation (following in vitro challenges/insults to the cells)...
February 22, 2018: Sports Medicine
Gautam Pareek, Ruth E Thomas, Leo J Pallanck
The progressive accumulation of dysfunctional mitochondria is implicated in aging and in common diseases of the elderly. To oppose this occurrence, organisms employ a variety of strategies, including the selective degradation of oxidatively damaged and misfolded mitochondrial proteins. Genetic studies in yeast indicate that the ATPase Associated with diverse cellular Activities (AAA+ ) family of mitochondrial proteases account for a substantial fraction of this protein degradation, but their metazoan counterparts have been little studied, despite the fact that mutations in the genes encoding these proteases cause a variety of human diseases...
February 21, 2018: Cell Death & Disease
Hongbo Gao, Yi-Fan Li
Denervation induces skeletal muscle atrophy, which primarily impairs oxidative slow twitch fibers. The underlying mechanism of this phenomenon, however, remains to be addressed. We hypothesize that denervation-induced fiber-specific atrophy may result from the distinct activities of different signaling pathways that are involved in protein synthesis and degradation in fast- and slow-twitch fibers. In this study, 1-month-old male mice were subjected to unilateral sciatic denervation for 4 days. Fast-twitch muscle extensor digitorum longus (EDL) and slow-twitch muscle soleus were collected from the denervated side and the control side of hind limbs...
February 2018: Physiological Reports
Huan T Nguyen, Satoru Noguchi, Kazuma Sugie, Yoshiyuki Matsuo, Chuyen T H Nguyen, Hitoshi Koito, Ichiro Shiojima, Ichizo Nishino, Hiroyasu Tsukaguchi
Lysosomal associated membrane protein 2 (LAMP2) is physiologically implicated in autophagy. A genetic LAMP2 defect causes Danon disease, which consists of two major phenotypes of myopathy and cardiomyopathy. In addition, arteriopathy may manifest on rare occasions but the pathological basis remains unknown. We encountered two Danon families that developed small-vessel vasculopathy in the coronary or cerebral arteries. To investigate the underlying mechanisms, we characterized the biological features of LAMP-2-deficient mice and cultured cells...
February 20, 2018: Scientific Reports
Elisa X Y Lim, Aroon Supramaniam, Hayman Lui, Peta Coles, Wai Suet Lee, Xiang Liu, Penny A Rudd, Lara J Herrero
Arthritogenic alphavirus infections often result in debilitating musculoskeletal disorders that affect the joints, muscle, and bone. In order to evaluate the infection profile of primary human skeletal muscle and chondrocyte cells to Ross River virus (RRV) in vitro, cells were infected at a multiplicity of infection (MOI) of 1 over a period of two days. Viral titers were determined by plaque assay and cytokine expression by Bio-Plex® assays using the supernatants harvested. Gene expression studies were conducted using total RNA isolated from cells...
February 15, 2018: Viruses
YouJin Lee, Per Harald Jonson, Jaakko Sarparanta, Johanna Palmio, Mohona Sarkar, Anna Vihola, Anni Evilä, Tiina Suominen, Sini Penttilä, Marco Savarese, Mridul Johari, Marie-Christine Minot, David Hilton-Jones, Paul Maddison, Patrick Chinnery, Jens Reimann, Cornelia Kornblum, Torsten Kraya, Stephan Zierz, Carolyn Sue, Hans Goebel, Asim Azfer, Stuart H Ralston, Peter Hackman, Robert C Bucelli, J Paul Taylor, Conrad C Weihl, Bjarne Udd
Multisystem proteinopathy (MSP) involves disturbances of stress granule (SG) dynamics and autophagic protein degradation that underlie the pathogenesis of a spectrum of degenerative diseases that affect muscle, brain, and bone. Specifically, identical mutations in the autophagic adaptor SQSTM1 can cause varied penetrance of 4 distinct phenotypes: amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Paget's disease of the bone, and distal myopathy. It has been hypothesized that clinical pleiotropy relates to additional genetic determinants, but thus far, evidence has been lacking...
February 19, 2018: Journal of Clinical Investigation
Donghwa Kim, Soomin Cho, Jung A Woo, Stephen B Liggett
β2 -Adrenergic receptors (β2 ARs) desensitize during continuous agonist activation, which manifests clinically as tachyphylaxis. β-Agonist desensitization of β2 ARs in human airway smooth muscle (HASM) cells is recognized in the treatment of asthma and may be related to poor outcomes. Rapid events in desensitization include receptor phosphorylation and internalization, but mechanisms responsible for the decrease in receptor protein after prolonged agonist exposure (down-regulation) are ill defined. The microRNA (miRNA) let-7f regulates β2 AR expression by translational repression...
February 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Nobuki Moriya, Mitsunori Miyazaki
Skeletal muscle mass is determined by the net dynamic balance between protein synthesis and degradation. Although the Akt/mechanistic target of rapamycin (mTOR)-dependent pathway plays an important role in promoting protein synthesis and subsequent skeletal muscle hypertrophy, the precise molecular regulation of mTOR activity by the upstream protein kinase Akt is largely unknown. In addition, the activation of satellite cells has been indicated as a key regulator of muscle mass. However, the requirement of satellite cells for load-induced skeletal muscle hypertrophy is still under intense debate...
February 14, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Xingwang Xie, Xueyan Wang, Weijia Liao, Ran Fei, Nan Wu, Xu Cong, Qian Chen, Lai Wei, Yu Wang, Hongsong Chen
BACKGROUND: Identification of novel MDM2 or p53 binding proteins may reveal undefined oncogenes, tumor suppressors, signaling pathways and possible treatment targets. METHODS: By means of immunoprecipitation and Mass Spectrometry analysis, we aimed to identify novel regulators of the MDM2-p53 pathway. We further clarified the impact of MYL6B on the p53 protein level and on the process of apoptosis. We also investigated the role of MYL6B in hepatocellular carcinoma by clone formation assay and by determining the correlation between its expression and prognosis of HCC patients...
February 13, 2018: Journal of Experimental & Clinical Cancer Research: CR
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