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https://www.readbyqxmd.com/read/28533928/leucine-nicotinic-acid-synergy-stimulates-ampk-sirt1-signaling-and-regulates-lipid-metabolism-and-lifespan-in-caenorhabditis-elegans-and-hyperlipidemia-and-atherosclerosis-in-mice
#1
Antje Bruckbauer, Jheelam Banerjee, Quiang Cao, Xin Cui, Jia Jing, Lin Zha, Fenfen Li, Bingzhong Xue, Hang Shi, Michael B Zemel
BACKGROUND/AIMS: Nicotinic acid (NA), a lipid-lowering drug, serves as a source of NAD(+), the cofactor for Sirt1. Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Therefore, we tested the interactive effects of leucine and low dose NA on AMPK/Sirt1 signaling and downstream effects of lipid metabolism in cell culture, C. elegans and mice. METHODS: LDL-receptor knockout mice were fed an atherogenic Western diet supplemented with leucine (24 g/kg diet) and sub-therapeutic NA combinations (50 mg/kg diet and 250 mg/kg diet) or low therapeutic NA (1000 mg/kg diet) for 8 weeks to evaluate markers of hyperlipidemia and atherosclerosis...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28533404/repression-of-phosphatidylinositol-transfer-protein-%C3%AE-ameliorates-the-pathology-of-duchenne-muscular-dystrophy
#2
Natassia M Vieira, Janelle M Spinazzola, Matthew S Alexander, Yuri B Moreira, Genri Kawahara, Devin E Gibbs, Lillian C Mead, Sergio Verjovski-Almeida, Mayana Zatz, Louis M Kunkel
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531892/emery-dreifuss-muscular-dystrophy-associated-mutant-forms-of-lamin-a-recruit-the-stress-responsive-protein-ankrd2-into-the-nucleus-affecting-the-cellular-response-to-oxidative-stress
#3
Silvia Angori, Cristina Capanni, Georgine Faulkner, Camilla Bean, Giuseppe Boriani, Giovanna Lattanzi, Vittoria Cenni
BACKGROUND: Ankrd2 is a stress responsive protein mainly expressed in muscle cells. Upon the application of oxidative stress, Ankrd2 translocates into the nucleus where it regulates the activity of genes involved in cellular response to stress. Emery-Dreifuss Muscular Dystrophy 2 (EDMD2) is a muscular disorder caused by mutations of the gene encoding lamin A, LMNA. As well as many phenotypic abnormalities, EDMD2 muscle cells also feature a permanent basal stress state, the underlying molecular mechanisms of which are currently unclear...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28531105/high-mobility-group-box-1-disrupts-metabolic-function-with-cigarette-smoke-exposure-in-a-ceramide-dependent-manner
#4
Oliver J Taylor, Mikayla O Thatcher, Sheryl T Carr, Jonathan L Gibbs, Annie M Trumbull, Mitchell E Harrison, Duane R Winden, Mackenzie J Pearson, Trevor S Tippetts, William L Holland, Paul R Reynolds, Benjamin T Bikman
We have previously found that cigarette smoke disrupts metabolic function, in part, by increasing muscle ceramide accrual. To further our understanding of this, we sought to determine the role of the cytokine high-mobility group box 1 (HMGB1), which is increased with smoke exposure, in smoke-induced muscle metabolic perturbations. To test this theory, we determined HMGB1 from lungs of human smokers, as well as from lung cells from mice exposed to cigarette smoke. We also treated cells and mice directly with HMGB1, in the presence or absence of myriocin, an inhibitor of serine palmitoyltransferase, the rate-limiting enzyme in ceramide biosynthesis...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28526321/effects-of-dehp-and-its-metabolite-mehp-on-insulin-signalling-and-proteins-involved-in-glut4-translocation-in-cultured-l6-myotubes
#5
Mangala Priya Viswanathan, Vigneswari Mullainadhan, Mayilvanan Chinnaiyan, Balasubramanian Karundevi
Di-(2-ethylhexyl)phthalate (DEHP) is the plasticizer used in variety of medical and consumer products to impart structural flexibility. DEHP and its primary metabolite mono-(2-ethyl hexyl)phthalate (MEHP) posed a considerable interest because of their contribution to insulin resistance, type-2 diabetes and obesity. Experimental and epidemiological data have shown that DEHP affects blood glucose homeostasis. However, direct effect of DEHP and its metabolite MEHP on insulin signal transduction and glucose transporter 4 (GLUT4) translocation remain obscure...
May 16, 2017: Toxicology
https://www.readbyqxmd.com/read/28520772/the-chicken-embryo-as-an-efficient-model-to-test-the-function-of-muscle-fusion-genes-in-amniotes
#6
Daniel Sieiro, Nadège Véron, Christophe Marcelle
The fusion of myoblasts into multinucleated myotubes is a crucial step of muscle growth during development and of muscle repair in the adult. While multiple genes were shown to play a role in this process, a vertebrate model where novel candidates can be tested and analyzed at high throughput and relative ease has been lacking. Here, we show that the early chicken embryo is a fast and robust model in which functional testing of muscle fusion candidate genes can be performed. We have used known modulators of muscle fusion, Rac1 and Cdc42, along with the in vivo electroporation of integrated, inducible vectors, to show that the chicken embryo is a suitable model in which their function can be tested and quantified...
2017: PloS One
https://www.readbyqxmd.com/read/28515477/cancer-cachexia-associates-with-a-systemic-autophagy-inducing-activity-mimicked-by-cancer-cell-derived-il-6-trans-signaling
#7
Kristine Pettersen, Sonja Andersen, Simone Degen, Valentina Tadini, Joël Grosjean, Shinji Hatakeyama, Almaz N Tesfahun, Siver Moestue, Jana Kim, Unni Nonstad, Pål R Romundstad, Frank Skorpen, Sveinung Sørhaug, Tore Amundsen, Bjørn H Grønberg, Florian Strasser, Nathan Stephens, Dag Hoem, Anders Molven, Stein Kaasa, Kenneth Fearon, Carsten Jacobi, Geir Bjørkøy
The majority of cancer patients with advanced disease experience weight loss, including loss of lean body mass. Severe weight loss is characteristic for cancer cachexia, a condition that significantly impairs functional status and survival. The underlying causes of cachexia are incompletely understood, and currently no therapeutic approach can completely reverse the condition. Autophagy coordinates lysosomal destruction of cytosolic constituents and is systemically induced by starvation. We hypothesized that starvation-mimicking signaling compounds secreted from tumor cells may cause a systemic acceleration of autophagy during cachexia...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28512793/5-azacytidine-mediated-hmsc-behaviour-on-electrospun-scaffolds-for-skeletal-muscle-regeneration
#8
Ines Fasolino, Vincenzo Guarino, Valentina Cirillo, Luigi Ambrosio
Incomplete regeneration after trauma or muscular dysfunction is a common problem in muscle replacement therapies. Recent approaches in tissue engineering allow for the replication of skeletal muscle structure and function in vitro and in vivo by molecular therapies and implantable scaffolds which properly address muscle cells towards myotube differentiation and maturation. Here, we investigate the in vitro response of human Mesenchymal Stem Cells (hMSC) on electrospun fibres made of Polycaprolactone (PCL) in the presence of 5-azacytidine (5-AZA) to evaluate how fibrous network may influence the therapeutic effect of drug during in vitro myogenesis...
May 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28511130/design-synthesis-and-biological-evaluation-of-uncharged-catechol-derivatives-as-selective-inhibitors-of-ptp1b
#9
Xiang-Qian Li, Qi Xu, Jiao Luo, Li-Jun Wang, Bo Jiang, Ren-Shuai Zhang, Da-Yong Shi
Protein tyrosine phosphatases 1B (PTP1B) is a promising and validated therapeutic target to effectively treat T2DM and obesity. However, the development of charged PTP1B inhibitors was restricted due to their low cell permeability and poor bioavailability. Based on active natural products, two series of uncharged catechol derivatives were identified as PTP1B inhibitors by targeting a secondary aryl phosphate-binding site as well as the catalytic site. The most potent inhibitor 22 showed an IC50 of 0.487 μM against PTP1B and strong selectivity (27-fold) over TCPTP...
May 3, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28506762/the-nuclear-phosphatase-scp4-regulates-foxo-transcription-factors-during-muscle-wasting-in-chronic-kidney-disease
#10
Xinyan Liu, Rizhen Yu, Lijing Sun, Giacomo Garibotto, Xia Lin, Yanlin Wang, Sandhya S Thomas, Rongshan Li, Zhaoyong Hu
Chronic kidney disease (CKD) and related inflammatory responses stimulate protein-energy wasting, a complication causing loss of muscle mass. Primarily, muscle wasting results from accelerated protein degradation via autophagic/lysosomal and proteasomal pathways, but mechanisms regulating these proteolysis pathways remain unclear. Since dephosphorylation of FoxOs regulates ubiquitin/proteasome protein metabolism, we tested whether a novel nuclear phosphatase, the small C-terminal domain phosphatase (SCP) 4, regulates FoxOs signaling and, in turn, muscle wasting...
May 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28501623/efficient-direct-conversion-of-human-fibroblasts-into-myogenic-lineage-induced-by-co-transduction-with-mycl-and-myod1
#11
Junko Wakao, Tsunao Kishida, Shigehisa Fumino, Koseki Kimura, Kenta Yamamoto, Shinichiro Kotani, Katsura Mizushima, Yuji Naito, Toshikazu Yoshikawa, Tatsuro Tajiri, Osam Mazda
The skeletal muscle consists of contractile myofibers and plays essential roles for maintenance of body posture, movement, and metabolic regulation. During the development and regeneration of the skeletal muscle tissue, the myoblasts fuse into multinucleated myotubes that subsequently form myofibers. Transplantation of myoblasts may make possible a novel regenerative therapy against defects or dysfunction of the skeletal muscle. It is reported that rodent fibroblasts are converted into myoblast-like cells and fuse to form syncytium after forced expression of exogenous myogenic differentiation 1 (MYOD1) that is a key transcription factor for myoblast differentiation...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28495800/mechanically-patterned-neuromuscular-junctions-in-a-dish-have-improved-functional-maturation
#12
Cassandra L Happe, Kevin P Tenerelli, Anastasia K Gromova, Frederic Kolb, Adam J Engler
Motor neuron (MN) diseases are progressive disorders resulting from degeneration of neuromuscular junctions (NMJs), which form the connection between MNs and muscle fibers. NMJ-in-a-dish models have been developed to examine human MN-associated dysfunction with disease; however such co-culture models have randomly oriented myotubes with immature synapses that contract asynchronously. Mechanically patterned (MP) extracellular matrix with alternating soft and stiff stripes improve current NMJ-in-a-dish models by inducing both mouse and human myoblast durotaxis to stripes where they aligned, differentiated, and fused into patterned myotubes...
May 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28491099/induction-of-pluripotent-stem-cells-from-a-manifesting-carrier-of-duchenne-muscular-dystrophy-and-characterization-of-their-x-inactivation-status
#13
Yuko Miyagoe-Suzuki, Takashi Nishiyama, Miho Nakamura, Asako Narita, Fusako Takemura, Satoru Masuda, Narihiro Minami, Kumiko Murayama, Hirofumi Komaki, Yu-Ichi Goto, Shin'ichi Takeda
Three to eight percent of female carriers of Duchenne muscular dystrophy (DMD) develop dystrophic symptoms ranging from mild muscle weakness to a rapidly progressive DMD-like muscular dystrophy due to skewed inactivation of X chromosomes during early development. Here, we generated human induced pluripotent stem cells (hiPSCs) from a manifesting female carrier using retroviral or Sendai viral (SeV) vectors and determined their X-inactivation status. Although manifesting carrier-derived iPS cells showed normal expression of human embryonic stem cell markers and formed well-differentiated teratomas in vivo, many hiPS clones showed bi-allelic expression of the androgen receptor (AR) gene and loss of X-inactivation-specific transcript and trimethyl-histone H3 (Lys27) signals on X chromosomes, suggesting that both X chromosomes of the hiPS cells are in an active state...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28490443/peripheral-insulin-resistance-in-ilk-depleted-mice-by-reduction-of-glut4-expression
#14
Marco Hatem-Vaquero, Mercedes Griera, Andrea Garcia-Jerez, Alicia Luengo, Julia Alvarez-Hernandez, Jose Antonio Rubio-Garcia, Laura Calleros, Diego Rodriguez-Puyol, Manuel Rodriguez-Puyol, Sergio de Frutos
The development of insulin resistance is characterized by the impairment of glucose uptake mediated by glucose transporter 4 (GLUT4). Extracellular matrix changes are induced when the metabolic dysregulation is sustained. The present work was devoted to analyze the possible link between the extracellular-to-intracellular mediator integrin linked kinase (ILK) and the peripheral tissue modification that leads to glucose homeostasis impairment. Mice with general depletion of ILK in adulthood (cKD-ILK) maintained in a chow diet exhibited increased glycaemia and insulinemia concurrently with a reduction of the expression and membranes presence of GLUT4 in the insulin-sensitive peripheral tissues compared with their wildtype littermates (WT)...
May 10, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28487439/roux-en-y-gastric-bypass-surgery-enhances-contraction-mediated-glucose-metabolism-in-primary-human-myotubes
#15
J Matthew Hinkley, Kai Zou, Sanghee Park, Kristen Turner, Donghai Zheng, Joseph A Houmard
Contractile activity (e.g. exercise) evokes numerous metabolic adaptations in human skeletal muscle including enhanced insulin action and substrate oxidation. However, there is inter-subject variation in the physiological responses to exercise, which may be linked with factors such as the degree of obesity. Roux-en-Y gastric bypass (RYGB) surgery reduces body mass in severely obese (BMI > 40 kg/m(2)) individuals; however, it is uncertain whether RYGB can potentiate responses to contractile activity in this potentially exercise-resistant population...
May 9, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28485891/%C3%AE-syntrophin-stabilises-catalase-to-reduce-endogenous-reactive-oxygen-species-levels-during-myoblast-differentiation
#16
Jae Yun Moon, Su Jin Choi, Cheol Ho Heo, Hwan Myung Kim, Hye Sun Kim
α-Syntrophin is a component of the dystrophin-glycoprotein complex that interacts with various intracellular signaling proteins in muscle cells. The α-syntrophin knock-down C2 cell line (SNKD), established by infecting lentivirus particles with α-syntrophin shRNA, is characterized by a defect in terminal differentiation and increase in cell death. Since myoblast differentiation is accompanied by intensive mitochondrial biogenesis, the generation of intracellular reactive oxygen species (ROS) is also increased during myogenesis...
May 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28485800/gdf11-does-not-improve-the-palmitate-induced-insulin-resistance-in-c2c12
#17
Y-Y Jing, D Li, F Wu, L-L Gong, R Li
OBJECTIVE: GDF11 (Growth Differentiation factor 11) has been reported to rejuvenate skeletal muscle, heart and brain in aged mice, and the aged skeletal muscle is closely related to insulin resistance. We wondered whether GDF11 has an effect on skeletal muscle insulin resistance. MATERIALS AND METHODS: High fat diet induced obese mice with insulin resistance were established in vivo. Palmitate-induced insulin resistance in C2C12 myotubes was established in vitro...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28485004/sialic-acid-expression-in-human-fetal-skeletal-muscle-during-limb-early-myogenesis
#18
Mirca Marini, Erica Sarchielli, Giorgia Donata Zappoli Thyrion, Stefano Ambrosini, Eleonora Sgambati
Investigations on animal models demonstrated that changes of sialic acid (SA) expression, particularly the polymeric form, in the skeletal muscle during embryonic and post-natal development seem to be related to muscle differentiation and functionality onset. The aim of this study was to evaluate the monomeric and polymeric SA expression in human skeletal muscle during early stages of fetal development, when important morphofunctional events occur. Specimens of fetal skeletal muscle from limb, between 9 and 12 weeks of gestation (wg), were obtained from 19 pregnant women...
May 9, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28483437/4-phenyl-butyric-acid-increases-particulate-hexokinase-activity-and-protects-against-ros-injury-in-l6-myotubes
#19
Michele Hinerasky da Silva, Flavia Letícia Martins Peçanha, Aline Machado de Oliveira, Wagner Seixas da-Silva
Hexokinase (HK) is the first enzyme in the glycolytic pathway and is responsible for glucose phosphorylation and fixation into the cell. HK (HK-II) is expressed in skeletal muscle and can be found in the cytosol or bound mitochondria, where it can protect cells against insults such as oxidative stress. 4-Phenyl butyric acid (4-PBA) is a chemical chaperone that inhibits endoplasmic reticulum stress and contributes to the restoring of glucose homeostasis. AIMS: Here, we decided to investigate whether HK activity and its interaction with mitochondria could be a target of 4-PBA action...
May 5, 2017: Life Sciences
https://www.readbyqxmd.com/read/28479722/influence-of-capsaicin-on-inflammatory-cytokines-induced-by-lipopolysaccharide-in-myoblast-cells-under-in-vitro-environment
#20
Ke Shang, Touseef Amna, Musarat Amina, Nawal M Al-Musayeib, Salem S Al-Deyab, Inho Hwang
BACKGROUND: ellular damage initiated by reactive oxygen species (ROS) is the main cause of numerous severe diseases and therefore for this reason, the natural antioxidants have note worthy significance in human health. Capsaicin possesses noteworthy analgesic and anti-inflammatory properties. It also possesses healing effects for treatment of arthritis, diabetic neuropathy, gastric lesions, and cardiac excitability that is why it is incorporated in creams and gels. OBJECTIVE: The present study was carried out to estimate the in vitro antioxidant and ROS scavenging activities of capsaicin against muscle precursor cells...
January 2017: Pharmacognosy Magazine
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