scholarly journals Role of Phosphoinositide 3-OH Kinase p110β in Skeletal Myogenesis

2015 â—½  
Vol 35 (7) â—½  
pp. 1182-1196 â—½  
Author(s):  
Ronald W. Matheny â—½  
Melissa A. Riddle-Kottke â—½  
Luis A. Leandry â—½  
Christine M. Lynch â—½  
Mary N. Abdalla â—½  
...  
Keyword(s):  
Skeletal Muscle â—½  
C2c12 Cells â—½  
Muscle Size â—½  
Whole Body â—½  
Myoblast Differentiation â—½  
Delayed Differentiation â—½  
Conditional Deletion â—½  
Glucose Tolerant â—½  
Old Mice

Phosphoinositide 3-OH kinase (PI3K) regulates a number of developmental and physiologic processes in skeletal muscle; however, the contributions of individual PI3K p110 catalytic subunits to these processes are not well-defined. To address this question, we investigated the role of the 110-kDa PI3K catalytic subunit β (p110β) in myogenesis and metabolism. In C2C12 cells, pharmacological inhibition of p110β delayed differentiation. We next generated mice with conditional deletion of p110β in skeletal muscle (p110β muscle knockout [p110β-mKO] mice). While young p110β-mKO mice possessed a lower quadriceps mass and exhibited less strength than control littermates, no differences in muscle mass or strength were observed between genotypes in old mice. However, old p110β-mKO mice were less glucose tolerant than old control mice. Overexpression of p110β accelerated differentiation in C2C12 cells and primary human myoblasts through an Akt-dependent mechanism, while expression of kinase-inactive p110β had the opposite effect. p110β overexpression was unable to promote myoblast differentiation under conditions of p110α inhibition, but expression of p110α was able to promote differentiation under conditions of p110β inhibition. These findings reveal a role for p110β during myogenesis and demonstrate that long-term reduction of skeletal muscle p110β impairs whole-body glucose tolerance without affecting skeletal muscle size or strength in old mice.

Determinants of maximal whole-body fat oxidation in elite cross-country skiers: Role of skeletal muscle mitochondria

10.1111/sms.13298 â—½  
2018 â—½  
Vol 28 (12) â—½  
pp. 2494-2504 â—½  
Author(s):  
Sune Dandanell â—½  
Anne-Kristine Meinild-Lundby â—½  
Andreas B. Andersen â—½  
Paul F. Lang â—½  
Laura Oberholzer â—½  
...  
Keyword(s):  
Skeletal Muscle â—½  
Body Fat â—½  
Fat Oxidation â—½  
Whole Body â—½  
Muscle Mitochondria â—½  
Skeletal Muscle Mitochondria â—½  
Cross Country

PGC-1α is associated with C2C12 Myoblast differentiation

Open Life Sciences â—½  
2014 â—½  
Vol 9 (11) â—½  
pp. 1030-1036 â—½  
Author(s):  
Yaqiu Lin â—½  
Yanying Zhao â—½  
Ruiwen Li â—½  
Jiaqi Gong â—½  
Yucai Zheng â—½  
...  
Keyword(s):  
Mrna Level â—½  
Biological Significance â—½  
C2c12 Cells â—½  
Myoblast Differentiation â—½  
C2c12 Myoblast â—½  
Mrna Levels â—½  
Transfected Cells â—½  
Myosin Heavy Chain Isoform â—½  
Important Mediator

AbstractPGC-1α has been implicated as an important mediator of functional capacity of skeletal muscle. However, the role of PGC-1α in myoblast differentiation remains unexplored. In the present study, we observed a significant up-regulation of PGC-1α expression during the differentiation of murine C2C12 myoblast. To understand the biological significance of PGC-1α up-regulation in myoblast differentiation, C2C12 cells were transfected with murine PGC-1α cDNA and siRNA targeting PGC-1α, respectively. PGC-1α over-expressing clones fused to form typical myotubes with higher mRNA level of myosin heavy chain isoform I (MyHCI) and lower MyHCIIX. No obvious differentiation was observed in PGC-1α-targeted siRNA-transfected cells with marked decrement of mRNA levels of MyHCI and MyHCIIX. Furthermore, PGC-1α increased the expression of MyoD and MyoG in C2C12 cells, which controlled the commitment of precursor cells to myotubes. These results indicate that PGC-1α is associated with myoblast differentiation and elevates MyoD and MyoG expression levels in C2C12 cells.

Anemic Hypoxemia Reduces Myoblast Proliferation and Muscle Growth in Late Gestation Fetal Sheep

2021 â—½  
Author(s):  
Paul J. Rozance â—½  
Stephanie R Wesolowski â—½  
Sonnet S. Jonker â—½  
Laura D Brown
Keyword(s):  
Skeletal Muscle â—½  
Mrna Expression â—½  
Muscle Growth â—½  
Late Gestation â—½  
Whole Body â—½  
Myoblast Differentiation â—½  
Fetal Sheep â—½  
Body Protein â—½  
Skeletal Muscle Growth â—½  
Myoblast Proliferation

Fetal skeletal muscle growth requires myoblast proliferation, differentiation, and fusion into myofibers in addition to protein accretion for fiber hypertrophy. Oxygen is an important regulator of this process. Therefore, we hypothesized that fetal anemic hypoxemia would inhibit skeletal muscle growth. Studies were performed in late gestation fetal sheep that were bled to anemic, and therefore hypoxemic, conditions beginning at ~125 days of gestation (term = 148 days) for 9 ± 0 days (n=19) and compared to control fetuses (n=16). A metabolic study was performed on gestational day ~134 to measure fetal protein kinetic rates. Myoblast proliferation and myofiber area were determined in biceps femoris (BF), tibialis anterior (TA), and flexor digitorum superficialis (FDS) muscles. mRNA expression of muscle regulatory factors was determined in BF. Fetal arterial hematocrit and oxygen content were 28% and 52% lower, respectively, in anemic fetuses. Fetal weight and whole-body protein synthesis, breakdown, and accretion rates were not different between groups. Hindlimb length, however, was 7% shorter in anemic fetuses. TA and FDS muscles weighed less and FDS myofiber area was smaller in anemic fetuses compared to controls. The percentage of Pax7+ myoblasts that expressed Ki67 was lower in BF and tended to be lower in FDS from anemic fetuses indicating reduced myoblast proliferation. There was less MYOD and MYF6 mRNA expression in anemic vs. control BF consistent with reduced myoblast differentiation. These results indicate that fetal anemic hypoxemia reduced muscle growth. We speculate that fetal muscle growth may be improved by strategies that increase oxygen availability.

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

2020 â—½  
Vol 21 (5) â—½  
pp. 1628 â—½  
Author(s):  
Keisuke Hitachi â—½  
Masashi Nakatani â—½  
Shiori Funasaki â—½  
Ikumi Hijikata â—½  
Mizuki Maekawa â—½  
...  
Keyword(s):  
Skeletal Muscle â—½  
Muscle Mass â—½  
Muscle Atrophy â—½  
Skeletal Muscle Mass â—½  
Muscle Size â—½  
Skeletal Muscle Atrophy â—½  
Myostatin Gene â—½  
Expression Levels â—½  
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.

scholarly journals Dermatopontin in Skeletal Muscle Extracellular Matrix Regulates Myogenesis

Cells â—½  
2019 â—½  
Vol 8 (4) â—½  
pp. 332 â—½  
Author(s):  
Kim â—½  
Ahmad â—½  
Shaikh â—½  
Jan â—½  
Seo â—½  
...  
Keyword(s):  
Extracellular Matrix â—½  
In Silico â—½  
State Of The Art â—½  
Myogenic Differentiation â—½  
3D Structure â—½  
Inhibitory Effect â—½  
C2c12 Cells â—½  
Myoblast Differentiation â—½  
Protein Protein Interaction

Dermatopontin (DPT) is an extensively distributed non-collagenous component of the extracellular matrix predominantly found in the dermis of the skin, and consequently expressed in several tissues. In this study, we explored the role of DPT in myogenesis and perceived that it enhances the cell adhesion, reduces the cell proliferation and promotes the myoblast differentiation in C2C12 cells. Our results reveal an inhibitory effect with fibronectin (FN) in myoblast differentiation. We also observed that DPT and fibromodulin (FMOD) regulate positively to each other and promote myogenic differentiation. We further predicted the 3D structure of DPT, which is as yet unknown, and validated it using state-of-the-art in silico tools. Furthermore, we explored the in-silico protein-protein interaction between DPT-FMOD, DPT-FN, and FMOD-FN, and perceived that the interaction between FMOD-FN is more robust than DPT-FMOD and DPT-FN. Taken together, our findings have determined the role of DPT at different stages of the myogenic process.

scholarly journals Mechanisms of sympathetic restraint in human skeletal muscle during exercise: role of α-adrenergic and nonadrenergic mechanisms

2020 â—½  
Vol 319 (1) â—½  
pp. H192-H202
Author(s):  
Alexander B. Hansen â—½  
Gilbert Moralez â—½  
Steven A. Romero â—½  
Christopher Gasho â—½  
Michael M. Tymko â—½  
...  
Keyword(s):  
Skeletal Muscle â—½  
Adrenergic Receptors â—½  
Whole Body â—½  
Cycle Exercise â—½  
Vascular Conductance â—½  
Hand Grip â—½  
Vasodilatory Response â—½  
Sympathetic Vasoconstriction â—½  
Exercise Induced

Sympathetic restraint of vascular conductance to inactive skeletal muscle is critical to maintain blood pressure during moderate- to high-intensity whole body exercise. This investigation shows that cycle exercise-induced restraint of inactive skeletal muscle vascular conductance occurs primarily because of activation of α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction restrains the subsequent vasodilatory response to hand-grip exercise; however, the restraint of active skeletal muscle vasodilation was in part due to nonadrenergic mechanisms. We conclude that α-adrenergic receptors are the primary but not exclusive mechanism by which sympathetic vasoconstriction restrains blood flow in humans during whole body exercise and that metabolic activity modulates the contribution of α-adrenergic receptors.

Effects of resistance training and chromium picolinate on body composition and skeletal muscle in older men

1999 â—½  
Vol 86 (1) â—½  
pp. 29-39 â—½  
Author(s):  
Wayne W. Campbell â—½  
Lyndon J. O. Joseph â—½  
Stephanie L. Davey â—½  
Deanna Cyr-Campbell â—½  
Richard A. Anderson â—½  
...  
Keyword(s):  
Skeletal Muscle â—½  
Body Composition â—½  
Resistance Training â—½  
Muscle Power â—½  
Older Men â—½  
Muscle Size â—½  
Whole Body â—½  
Chromium Picolinate â—½  
High Dose â—½  
Repetition Maximum

The effects of chromium picolinate (CrPic) supplementation and resistance training (RT) on skeletal muscle size, strength, and power and whole body composition were examined in 18 men (age range 56–69 yr). The men were randomly assigned (double-blind) to groups ( n = 9) that consumed either 17.8 μmol Cr/day (924 μg Cr/day) as CrPic or a low-Cr placebo for 12 wk while participating twice weekly in a high-intensity RT program. CrPic increased urinary Cr excretion ∼50-fold ( P < 0.001). RT-induced increases in muscle strength ( P < 0.001) were not enhanced by CrPic. Arm-pull muscle power increased with RT at 20% ( P = 0.016) but not at 40, 60, or 80% of the one repetition maximum, independent of CrPic. Knee-extension muscle power increased with RT at 20, 40, and 60% ( P < 0.001) but not at 80% of one repetition maximum, and the placebo group gained more muscle power than did the CrPic group (RT by supplemental interaction, P < 0.05). Fat-free mass ( P < 0.001), whole body muscle mass ( P < 0.001), and vastus lateralis type II fiber area ( P < 0.05) increased with RT in these body-weight-stable men, independent of CrPic. In conclusion, high-dose CrPic supplementation did not enhance muscle size, strength, or power development or lean body mass accretion in older men during a RT program, which had significant, independent effects on these measurements.

ROLE OF NA+, K+-ATPase IN MUSCULAR ENERGY EXPENDITURE OF WARM- AND COLD-EXPOSED SHEEP

10.4141/cjas82-012 â—½  
1982 â—½  
Vol 62 (1) â—½  
pp. 123-132 â—½  
Author(s):  
V. A. GREGG â—½  
L. P. MILLIGAN
Keyword(s):  
Skeletal Muscle â—½  
Energy Expenditure â—½  
Cold Exposure â—½  
Whole Body â—½  
Random Group â—½  
Key Words Skeletal Muscle â—½  
Maximum Inhibition â—½  
Functional Membrane

The role of Na+, K+-ATPase in the energy expenditure of sheep skeletal muscle and the influence of exposure to cold on this role were studied. An in vitro preparation of muscle was developed that achieved O2 availability and a functional membrane potential. A 10−6 M concentration of ouabain yielded a maximum inhibition of respiration of 38.9 ± 1.8% using muscle preparations from a random group of sheep. Whole body and muscle O2 consumptions and ouabain-sensitive muscle respiration were measured for warm- and cold-exposed sheep fed at maintenance or 1150 g of alfalfa pellets per day. Cold exposure increased whole body and muscle O2 consumption. Inhibition of respiration by ouabain was 37.6 ± 1.2% and 41.0 ± 3.6% for warm- and cold-exposed sheep fed at maintenance, and 28.5 ± 4.0% and 45.0 ± 4.0% for warm- and cold-exposed sheep fed 1150 g of alfalfa pellets per day. The increase in the ouabain-sensitive component of respiration accounted for 48–79% of the increased O2 consumption of muscle from cold-exposed sheep. It was concluded that the Na+, K+-ATPase of sheep muscle is a major means of energy expenditure and has an important role in the increased thermogenesis resulting from cold exposure. Key words: Skeletal muscle, Energy expenditure, muscle respiration, cold thermogenesis, sodium-potassium transport

scholarly journals Zfp422 promotes skeletal muscle differentiation by regulating EphA7 to induce appropriate myoblast apoptosis

2019 â—½  
Vol 27 (5) â—½  
pp. 1644-1659 â—½  
Author(s):  
Yaping Nie â—½  
Shufang Cai â—½  
Renqiang Yuan â—½  
Suying Ding â—½  
Xumeng Zhang â—½  
...  
Keyword(s):  
Skeletal Muscle â—½  
Zinc Finger â—½  
Muscle Development â—½  
Zinc Finger Protein â—½  
Critical Role â—½  
Muscle Differentiation â—½  
C2c12 Cells â—½  
Myoblast Differentiation â—½  
Skeletal Muscle Differentiation â—½  
Finger Protein

Abstract Zinc finger protein 422 (Zfp422) is a widely expressed zinc finger protein that serves as a transcriptional factor to regulate downstream gene expression, but until now, little is known about its roles in myogenesis. We found here that Zfp422 plays a critical role in skeletal muscle development and regeneration. It highly expresses in mouse skeletal muscle during embryonic development. Specific knockout of Zfp422 in skeletal muscle impaired embryonic muscle formation. Satellite cell-specific Zfp422 deletion severely inhibited muscle regeneration. Myoblast differentiation and myotube formation were suppressed in Zfp422-deleted C2C12 cells, isolated primary myoblasts, and satellite cells. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) revealed that Zfp422 regulated ephrin type-A receptor 7 (EphA7) expression by binding an upstream 169-bp DNA sequence, which was proved to be an enhancer of EphA7. Knocking EphA7 down in C2C12 cells or deleting Zfp422 in myoblasts will inhibit cell apoptosis which is required for myoblast differentiation. These results indicate that Zfp422 is essential for skeletal muscle differentiation and fusion, through regulating EphA7 expression to maintain proper apoptosis.

scholarly journals Doxycycline Inhibits IL-17-Stimulated MMP-9 Expression by Downregulating ERK1/2 Activation: Implications in Myogenic Differentiation

2016 â—½  
Vol 2016 â—½  
pp. 1-11 â—½  
Author(s):  
Hristina Obradović â—½  
Jelena Krstić â—½  
Tamara Kukolj â—½  
Drenka Trivanović â—½  
Ivana Okić Đorđević â—½  
...  
Keyword(s):  
Inflammatory Diseases â—½  
Myogenic Differentiation â—½  
C2c12 Cell â—½  
C2c12 Cells â—½  
Myoblast Differentiation â—½  
Interleukin 17 â—½  
Myoblast Cells â—½  
Pathological Consequence â—½  
Muscle Remodeling

Interleukin 17 (IL-17) is a cytokine with pleiotropic effects associated with several inflammatory diseases. Although elevated levels of IL-17 have been described in inflammatory myopathies, its role in muscle remodeling and regeneration is still unknown. Excessive extracellular matrix degradation in skeletal muscle is an important pathological consequence of many diseases involving muscle wasting. In this study, the role of IL-17 on the expression of matrix metalloproteinase- (MMP-) 9 in myoblast cells was investigated. The expression of MMP-9 after IL-17 treatment was analyzed in mouse myoblasts C2C12 cell line. The increase in MMP-9 production by IL-17 was concomitant with its capacity to inhibit myogenic differentiation of C2C12 cells. Doxycycline (Doxy) treatment protected the myogenic capacity of myoblasts from IL-17 inhibition and, moreover, increased myotubes hypertrophy. Doxy blocked the capacity of IL-17 to stimulate MMP-9 production by regulating IL-17-induced ERK1/2 MAPK activation. Our results imply that MMP-9 mediates IL-17’s capacity to inhibit myoblast differentiation during inflammatory diseases and indicate that Doxy can modulate myoblast response to inflammatory induction by IL-17.

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