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(Muscle Protein) AND (Degradation or breakdown or atrophy or loss)

I M Winje, X Sheng, K-A Hansson, A Solbrå, S Tennøe, F Saatcioglu, J C Bruusgaard, K Gundersen
AIM: Cachexia is a severe wasting disorder involving loss of body- and muscle mass reducing survival and quality of life in cancer patients. We aim at determining if cachexia is a mere perturbation of the protein balance or if the condition also involves a degenerative loss myonuclei within the fiber syncytia or loss of whole muscle fibers. METHODS: We induced cachexia by xenografting PC3 prostate cancer cells in nu/nu mice. Six weeks later, we counted myonuclei by in vivo microscopic imaging of single live fibers in the extensor digitorum longus muscle (EDL), and the EDL, soleus and tibialis anterior muscles were also harvested for ex vivo histology...
October 16, 2018: Acta Physiologica
Adam J Rudinsky, Laura M Harjes, Julie Byron, Dennis J Chew, Ramiro E Toribio, Catherine Langston, Valerie J Parker
BACKGROUND: Chronic kidney disease (CKD) is associated with morbidity and mortality in dogs. Plasma fibroblast growth factor-23 (FGF-23) concentration is an independent predictor of CKD progression and survival in cats and people with CKD. OBJECTIVES: To investigate the relationship among FGF-23, parathyroid hormone (PTH), vitamin D metabolites, and other clinical variables with survival time in dogs with CKD. ANIMALS: Twenty-seven azotemic CKD dogs...
October 16, 2018: Journal of Veterinary Internal Medicine
Tatsuya Osaki, Sebastien G M Uzel, Roger D Kamm
Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease involving loss of motor neurons (MNs) and muscle atrophy, still has no effective treatment, despite much research effort. To provide a platform for testing drug candidates and investigating the pathogenesis of ALS, we developed an ALS-on-a-chip technology (i.e., an ALS motor unit) using three-dimensional skeletal muscle bundles along with induced pluripotent stem cell (iPSC)-derived and light-sensitive channelrhodopsin-2-induced MN spheroids from a patient with sporadic ALS...
October 2018: Science Advances
Alberto Ferlin, Luca De Toni, Alexander I Agoulnik, Giorgia Lunardon, Andrea Armani, Sergia Bortolanza, Bert Blaauw, Marco Sandri, Carlo Foresta
Androgens are primarily involved in muscle growth, whilst disease-driven muscle wasting is frequently associated with hypogonadism. The Leydig cells of the testes also produce the peptide-hormone Insulin-like peptide 3 (INSL3). INSL3 displays anabolic activity on bone, a target tissue of androgens, and its plasma concentrations are diminished in male hypogonadism. Here we tested the role of INSL3 on muscle mass regulation, in physiological and pathological conditions. Studies on C2C12 cell line showed that INSL3, acting on his specific receptor RXFP2, promotes skeletal muscle protein synthesis through the Akt/mTOR/S6 pathway...
2018: Frontiers in Endocrinology
Deepak Bushan Raina, Irfan Qayoom, David Larsson, Ming Hao Zheng, Ashok Kumar, Hanna Isaksson, Lars Lidgren, Magnus Tägil
A metaphyseal bone defect due to infection, tumor or fracture leads to loss of cancellous and cortical bone. An animal model separating the cancellous and cortical healing was used with a combination of a macroporous gelatin-calcium sulphate-hydroxyapatite (Gel-CaS-HA) biomaterial as a cancellous defect filler, and a thin collagen membrane (CM) guiding cortical bone regeneration. The membrane was immobilized with bone morphogenic protein-2 (rhBMP-2) to enhance the osteoinductive properties. The Gel-CaS-HA cancellous defect filler contained both rhBMP-2 and a bisphosphonate, (zoledronate = ZA) to prevent premature callus resorption induced by the pro-osteoclast effect of rhBMP-2 alone...
October 4, 2018: Biomaterials
Kazuya Murata, Weizhe Lu, Misuzu Hashimoto, Natsumi Ono, Masafumi Muratani, Kana Nishikata, Jun-Dal Kim, Shizufumi Ebihara, Junji Ishida, Akiyoshi Fukamizu
Protein arginine methyltransferase 1 (PRMT1) catalyzes the asymmetric dimethylation of arginine residues in proteins and methylation of various RNA-binding proteins and is associated with alternative splicing in vitro. Although PRMT1 has essential in vivo roles in embryonic development, CNS development, and skeletal muscle regeneration, the functional importance of PRMT1 in the heart remains to be elucidated. Here, we report that juvenile cardiomyocyte-specific PRMT1-deficient mice develop severe dilated cardiomyopathy and exhibit aberrant cardiac alternative splicing...
October 2, 2018: iScience
Jing Han, Yang Tang, Mingjian Lu, Haiqing Hua
Background: Methionine aminopeptidase 2 (MetAP2) cleaves the initiator methionine from nascent peptides during translation. In both preclinical and clinical studies, the pharmacological inhibition of MetAP2 in obese subjects results in the suppression of food intake and body weight loss. However, the mechanism of action of body weight loss caused by MetAP2 inhibition remains to be elucidated, and the sites of action by pharmacological MetAP2 inhibition remain unknown. Methods: In the present study, a comprehensive analysis of the MetAP2 expression pattern in mice was performed...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Keiko Ohnari, Kazumasa Okada, Osamu Higuchi, Hidenori Matsuo, Hiroaki Adachi
An 82-year-old woman developed neck weakness and dysarthria with antibodies against acetylcholine receptor (AChR) and low-density lipoprotein receptor-related protein 4 (LRP4). Myasthenia gravis (MG) was diagnosed by edrophonium and repetitive nerve stimulation tests. Her symptoms resolved completely by immunotherapy. One year later, she presented with muscle weakness and bulbar palsy accompanied by atrophy and fasciculation. Her tendon reflexes were brisk, and Babinski's sign was positive. She was diagnosed with probable amyotrophic lateral sclerosis (ALS)...
2018: Internal Medicine
Eleni Theocharidou, Marianna Papademetriou, Andromachi Reklou, Alexandros Sachinidis, Chrisoula Boutari, Olga Giouleme
BACKGROUND: Statin treatment exhibits a beneficial effect on non-alcoholic fatty liver disease (NAFLD) and on cardiovascular disease (CVD) in patients with NAFLD. OBJECTIVE: The aim of this review is to summarize the role of proprotein convertase subtilisin kexin type-9(PCSK9) in the pathogenesis of NAFLD and discuss the effects of the new hypolipidaemic drugs PCSK9 inhibitors on NAFLD. RESULTS: Data indicates that high intrahepatic or circulating PCSK9 levels increase muscle and liver lipid storage, adipose energy storage and hepatic fatty acids, as well as triglycerides storage and secretion, thus contributing to the pathogenesis of NAFLD...
October 10, 2018: Current Pharmaceutical Design
Nirmaljeet Kaur, Prachi Gupta, Vikram Saini, Sandeep Sherawat, Sanjeev Gupta, Anita Dua, Vinod Kumar, Elisha Injeti, Ashwani Mittal
Skeletal muscle atrophy/wasting is associated with impaired protein metabolism in diverse physiological and pathophysiological conditions. Elevated levels of reactive oxygen species (ROS), disturbed redox status, and weakened antioxidant defense system are the major contributing factors toward atrophy. Regulation of protein metabolism by controlling ROS levels and its associated catabolic pathways may help in treating atrophy and related clinical conditions. Although cinnamaldehyde (CNA) enjoys the established status of antioxidant and its role in ROS management is reported, impact of CNA on skeletal muscle atrophy and related pathways is still unexplored...
October 14, 2018: Journal of Cellular Physiology
Marina Mekheal, Jennifer L Steiner, Charles H Lang
Ethanol produces a state of anabolic resistance in skeletal muscle; however, whether the heart displays a similar defect is unknown. Hence, the purpose of this study was to determine the impact of acute ethanol administration on the major signal transduction pathways in the heart that are responsible for regulating the protein synthetic and degradative response to refeeding. Adult male C57Bl/6 mice were fasted for 12 h. Mice were then either refed normal rodent chow for 30 min or a separate group of mice remained food deprived prior to administration of 3-g/kg ethanol...
April 18, 2018: Alcohol
David M Thomson
AMPK (5'-adenosine monophosphate-activated protein kinase) is heavily involved in skeletal muscle metabolic control through its regulation of many downstream targets. Because of their effects on anabolic and catabolic cellular processes, AMPK plays an important role in the control of skeletal muscle development and growth. In this review, the effects of AMPK signaling, and those of its upstream activator, liver kinase B1 (LKB1), on skeletal muscle growth and atrophy are reviewed. The effect of AMPK activity on satellite cell-mediated muscle growth and regeneration after injury is also reviewed...
October 11, 2018: International Journal of Molecular Sciences
Mengxin Cai, Qing'an Wang, Zhiwei Liu, Dandan Jia, Rui Feng, Zhenjun Tian
AIMS: Myocardial infarction (MI) is accompanied with skeletal muscle abnormalities. The aims are to explore an optimal exercise mode to improve cardiac function and prevent skeletal muscle atrophy, and detected the possible mechanisms of exercise-induced inhibition of muscle atrophy. MAIN METHODS: Rats were subjected to four weeks of different types of exercise after MI surgery (resistance training, RT; moderated-intensity continuous aerobic exercise, MCE and high-intensity intermittent aerobic exercise, HIA)...
October 9, 2018: Life Sciences
Marc Francaux, Louise Deldicque
During the course of life, muscle mass undergoes many changes in terms of quantity and quality. Skeletal muscle is a dynamic tissue able to hypertrophy or atrophy according to growth, ageing, physical activity, nutrition and health state. The purpose of the present review is to present the mechanisms by which exercise can induce changes in human skeletal muscle mass by modulating protein balance and regulating the fate of satellite cells. Exercise is known to exert transcriptional, translational and post-translational regulations as well as to induce epigenetic modifications and to control messenger RNA stability, which all contribute to the regulation of protein synthesis...
October 11, 2018: Pflügers Archiv: European Journal of Physiology
Ki Bum Park, Oh Kyoung Kwon, Wansik Yu
Purpose: This study evaluated midterm changes in body composition after open distal gastrectomy for early gastric cancer. Methods: Data from 138 gastric cancer patients who underwent open distal gastrectomy at Kyungpook National University Chilgok Hospital between January 2011 and December 2012 were collected and reviewed. Patients with pathological stage I gastric cancer and with no comorbidities at diagnosis were enrolled. Body composition data from segmental multifrequency bioelectrical impedance analysis were obtained preoperatively and at 1, 2, and 3 years after surgery...
October 2018: Annals of Surgical Treatment and Research
Fang-Hui Li, Lei Sun, Min Zhu, Tao Li, Hao-En Gao, Da-Shuai Wu, Ling Zhu, Rui Duan, Timon Cheng-Yi Liu
Sarcopenia is associated with loss of muscle mass and function as well as oxidative stress, chronic low-grade inflammatory status, and adipocytokine dysfunction. It has been reported that sarcopenia can be attenuated by exercise training. The purpose of this study was to evaluate whether long-term high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) protocols could differentially modulate changes in body composition, physical performance, inflammatory parameters, and adipocytokines in fat tissues and serum, as well as oxidative parameters and insulin-like growth factor 1 (IGF-1) levels in skeletal muscle tissue of aged rats...
October 9, 2018: Experimental Gerontology
Rika Ito, Masaki Higa, Ayumi Goto, Megumi Aoshima, Akihiro Ikuta, Kazuya Ohashi, Shingo Yokoyama, Yoshitaka Ohno, Tatsuro Egawa, Hirofumi Miyata, Katsumasa Goto
This study investigated the effects of AdipoRon, which is an agonist for adiponectin receptor 1 (AdipoR1) and AdipoR2, on the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells and skeletal muscle mass in C57BL/6J mice. AdipoRon suppressed the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells of C2C12 myotubes in a dose-dependent manner. Adiponectin-associated decline of protein content, diameter, and number of nuclei per myotube in C2C12 myotubes was partially rescued by knockdown of AdipoR1 and/or AdipoR2...
2018: PloS One
Chiara Ninfali, Laura Siles, Douglas S Darling, Antonio Postigo
Multiple physiopathological and clinical conditions trigger skeletal muscle atrophy through the induction of a group of proteins (atrogenes) that includes components of the ubiquitin-proteasome and autophagy-lysosomal systems. Atrogenes are induced by FOXO transcription factors, but their regulation is still not fully understood. Here, we showed that the transcription factor ZEB1, best known for promoting tumor progression, inhibits muscle atrophy and atrogene expression by antagonizing FOXO3-mediated induction of atrogenes...
October 10, 2018: Nucleic Acids Research
Abir El Sadik, Enas Mohamed, Ahmed El Zainy
Development and maturation of submandibular salivary glands are influenced by intrauterine diabetic environment. Several studies investigated the effects of diabetes on the salivary glands. However, the effects of maternal diabetes on the submandibular glands of the offspring was not properly examined. Therefore, the present study was designed to describe the changes in the development of the submandibular glands of the offspring of diabetic mothers. The submandibular glands of the offspring of Streptozotocin (STZ)-induced diabetic female rats were examined at two and four weeks after birth...
2018: PloS One
Gian Luca Vita, Francesca Polito, Rosaria Oteri, Roberto Arrigo, Anna Maria Ciranni, Olimpia Musumeci, Sonia Messina, Carmelo Rodolico, Rosa Maria Di Giorgio, Giuseppe Vita, M'Hammed Aguennouz
Hippo signaling pathway is considered a key regulator of tissue homeostasis, cell proliferation, apoptosis and it is involved in cancer development. In skeletal muscle, YAP, a downstream target of the Hippo pathway, is an important player in myoblast proliferation, atrophy/hypertrophy regulation, and in mechano-trasduction, transferring mechanical signals into transcriptional responses. We studied components of Hippo pathway in muscle specimens from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, limb-girdle muscular dystrophy type 2A and type 2B and healthy subjects...
2018: PloS One
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