Mixed lactate and caffeine compound increases satellite cell activity and anabolic signals for muscle hypertrophy

2015 ◽  
Vol 118 (6) ◽  
pp. 742-749 ◽  
Author(s):  
Yoshimi Oishi ◽  
Hayato Tsukamoto ◽  
Takumi Yokokawa ◽  
Keisuke Hirotsu ◽  
Mariko Shimazu ◽  
...  
Keyword(s):  
Satellite Cells ◽  
Cell Activity ◽  
Treadmill Running ◽  
C2c12 Cells ◽  
Protein Levels ◽  
Low Intensity ◽  
Proliferation And Differentiation ◽  
Total Dna ◽  
Low Intensity Exercise

We examined whether a mixed lactate and caffeine compound (LC) could effectively elicit proliferation and differentiation of satellite cells or activate anabolic signals in skeletal muscles. We cultured C2C12 cells with either lactate or LC for 6 h. We found that lactate significantly increased myogenin and follistatin protein levels and phosphorylation of P70S6K while decreasing the levels of myostatin relative to the control. LC significantly increased protein levels of Pax7, MyoD, and Ki67 in addition to myogenin, relative to control. LC also significantly increased follistatin expression relative to control and stimulated phosphorylation of mTOR and P70S6K. In an in vivo study, male F344/DuCrlCrlj rats were assigned to control (Sed, n = 10), exercise (Ex, n = 12), and LC supplementation (LCEx, n = 13) groups. LC was orally administered daily. The LCEx and Ex groups were exercised on a treadmill, running for 30 min at low intensity every other day for 4 wk. The LCEx group experienced a significant increase in the mass of the gastrocnemius (GA) and tibialis anterior (TA) relative to both the Sed and Ex groups. Furthermore, the LCEx group showed a significant increase in the total DNA content of TA compared with the Sed group. The LCEx group experienced a significant increase in myogenin and follistatin expression of GA relative to the Ex group. These results suggest that administration of LC can effectively increase muscle mass concomitant with elevated numbers of myonuclei, even with low-intensity exercise training, via activated satellite cells and anabolic signals.

scholarly journals Prolonged underfeeding of sheep increases myostatin and myogenic regulatory factor Myf-5 in skeletal muscle while IGF-I and myogenin are repressed

2003 ◽  
Vol 176 (3) ◽  
pp. 425-437 ◽  
Author(s):  
F Jeanplong ◽  
JJ Bass ◽  
HK Smith ◽  
SP Kirk ◽  
R Kambadur ◽  
...  
Keyword(s):  
Satellite Cells ◽  
Muscle Growth ◽  
Cell Activity ◽  
Nuclear Antigen ◽  
Myogenic Regulatory Factor ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Muscle Necrosis

The IGF axis is nutritionally sensitive in vivo and IGFs stimulate myoblast proliferation and differentiation in vitro, while myostatin inhibits these processes in vitro. We hypothesised that underfeeding would reversibly inhibit the myogenic activity of satellite cells in vivo together with decreased IGF-I and increased myostatin in muscle. Satellite cell activity was measured indirectly from the expression of proliferating cell nuclear antigen (PCNA) and the myogenic regulatory factors (MRFs), MyoD, Myf-5 and myogenin. Young sheep were underfed (30% of maintenance) and some killed after 1, 4, 12, 17, 21 and 22 weeks. Remaining underfed animals were then re-fed a control ration of pellets and killed after 2 days, and 1, 6 and 30 weeks. Expression of PCNA and MRFs decreased during the first week of underfeeding. This coincided with reduced IGF-I and myostatin mRNA, and processed myostatin. Subsequently, Myf-5, MyoD, myostatin mRNA and processed myostatin increased, suggesting that satellite cells may have become progressively quiescent. Long-term underfeeding caused muscle necrosis in some animals and IGF-I and MRF expression was increased in these, indicating the activation of satellite cells for muscle repair. Re-feeding initiated rapid muscle growth and increased expression of PCNA, IGF-I and the MRFs concurrently with decreased myostatin proteins. In conclusion, these data indicate that IGF-I and myostatin may work in a coordinated manner to regulate the proliferation, differentiation and quiescence of satellite cells in vivo.

scholarly journals Acute Low-Intensity Treadmill Running Upregulates the Expression of Intestinal Glucose Transporters via GLP-2 in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1735
Author(s):  
Kai Aoki ◽  
Takuji Suzuki ◽  
Fang Hui ◽  
Takuro Nakano ◽  
Koki Yanazawa ◽  
...  
Keyword(s):  
Small Intestine ◽  
Intestinal Tract ◽  
Glucose Transporter ◽  
Treadmill Running ◽  
Low Intensity ◽  
Glucose Transporter 2 ◽  
Intestinal Digestion ◽  
Glucagon Like Peptide ◽  
Low Intensity Exercise ◽  
Carbohydrate Digestion

The effects of exercise on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training increases the expression of molecules involved in carbohydrate digestion and absorption. Exercise was also shown to increase the blood concentration of glucagon-like peptide-2 (GLP-2), which regulates carbohydrate digestion and absorption in the small intestine. Therefore, we investigated the effects of exercise on the expression of molecules involved in intestinal digestion and absorption, including GLP-2. Six-week-old male mice were divided into a sedentary (SED) and low-intensity exercise (LEx) group. LEx mice were required to run on a treadmill (12.5 m/min, 1 h), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest, and plasma, jejunum, ileum, and colon samples were collected, followed by analysis via IHC, EIA, and immunoblotting. The levels of plasma GLP-2 and the jejunum expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter 2 (GLUT2) were higher in LEx mice. Thus, we showed that acute low-intensity exercise affects the expression of molecules involved in intestinal carbohydrate digestion and absorption via GLP-2. Our results suggest that exercise might be beneficial for small intestine function in individuals with intestinal frailty.

scholarly journals LOW-INTENSITY EXERCISE ENHANCES MUSCULAR ANDROGEN/ANDROGEN RECEPTOR TO INHIBIT MYOSTATIN PATHWAY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S85-S86
Author(s):  
Bo-Kyung Son ◽  
Masato Eto ◽  
Miya Oura ◽  
Masahiro Akishita
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Electric Pulse ◽  
Negative Regulator ◽  
Muscle Size ◽  
C2c12 Myotubes ◽  
Protein Levels ◽  
Low Intensity ◽  
Low Intensity Exercise ◽  
Response To Exercise

Abstract Background: Physical exercise is well documented to induce muscle size, strength, and energy metabolism. Although the contribution of systemic or local androgen in exercise-adapted muscle hypertrophy has been suggested, less is known about the molecular pathway of androgen in response to exercise. In the present study, we examined roles of androgen/androgen receptor (AR) after exercise, especially for the suppression of myostatin, a potent negative regulator of muscle mass. Methods and Results: To examine the effects of exercise, we employed low-intensity exercise in mice and electric pulse stimulation (EPS) in C2C12 myotubes. Both mRNA and protein levels of AR significantly increased in skeletal muscle of low-intensity exercised mice and C2C12 myotubes exposed to EPS. Production of testosterone and DHT from EPS-treated C2C12 myotubes was markedly increased. Of interest, we found that myostatin was clearly inhibited by EPS, and its inhibition was significantly abrogated by flutamide, a specific antagonist of AR. Furthermore, IL-6 and phospho-STAT3 (pSTAT3) expression, the downstream pathway of myostatin, were decreased by EPS and this was also reversed by flutamide. Similar downregulation of myostatin and IL-6 was seen in skeletal muscle of low-intensity exercised mice. Conclusion: Muscle AR expression and androgen production were increased by exercise and EPS treatment. As a mechanistical insight, it is suggested that AR inhibited myostatin expression transcriptionally, which downregulates IL-6/pSTAT3 pathway and thus contributes to the prevention of muscle degradation.

scholarly journals Androgen receptor regulates the proliferation of myoblasts under appropriate or excessive stretch through IGF-1 receptor mediated p38 and ERK1/2 pathways

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Shaoting Fu ◽  
Xiaojing Lin ◽  
Lijun Yin ◽  
Xiaohui Wang
Keyword(s):  
Androgen Receptor ◽  
Muscle Mass ◽  
Satellite Cells ◽  
C2c12 Cells ◽  
C2c12 Myoblasts ◽  
Excessive Exercise ◽  
L6 Cells ◽  
Proliferation And Differentiation ◽  
Exercise Induced ◽  
P38 Pathway

Abstract Background Androgen receptor (AR) exerts important roles in exercise-induced alterations of muscle mass, in which the proliferation and differentiation of satellite cells or myoblasts are crucial. Our previous study in C2C12 myoblasts demonstrated that 15% (mimic appropriate exercise) and 20% (mimic excessive exercise) stretches promoted and inhibited the proliferation respectively; and AR played a crucial role in 15% stretch-induced pro-proliferation through IGF-1-modulated PI3K/Akt, p38 and ERK1/2 pathways, but AR’s role in stretches-modulated proliferation of general myoblasts, especially 20% stretch, remains unclear, and the mechanisms need to be further clarified. Methods Firstly, the discrepancy in proliferation and the above indicators between L6 (without AR) and C2C12 (with AR) myoblasts were compared under 15% or 20% stretch. Then the influences of transfection AR or exogenous IGF-1 treatment on proliferation and these indicators were detected in stretched L6 myoblasts. Results (1) Under un-stretched state, the proliferation of L6 was slower than C2C12 cells. Furthermore, AR knockdown in C2C12 myoblasts repressed, while AR overexpression in L6 myoblasts promoted the proliferation. (2) 15% stretch-induced increases in the proliferation and activities of p38 and ERK1/2 were lower in L6 than C2C12 cells; AR overexpression enhanced the proliferation of 15% stretched L6 cells accompanied with the increases of p38 and ERK1/2 activities. (3) 20% stretch-induced anti-proliferation and inhibition of p38 activity were severer in L6 than C2C12 myoblasts; AR overexpression reversed the anti-proliferation of 20% stretch and enhanced p38 activity in L6 myoblasts. (4) In stretched L6 myoblasts, AR overexpression increased IGF-1R level despite no detectable IGF-1; and recombinant IGF-1 increased the proliferation, the level of IGF-1R, and the activities of p38 and ERK1/2 in 15% stretched L6 myoblasts. Conclusions The study demonstrated AR's crucial roles in stretches-regulated proliferation of myoblasts, and increased AR fulfilled 15% stretch's pro-proliferation via activating IGF-1R- p38 and ERK1/2 pathways while decreased AR achieved 20% stretch's anti-proliferation via inhibiting IGF-1R- p38 pathway, which is useful to understand in depth the role and mechanisms of AR in appropriate exercise increasing while excessive exercise decreasing muscle mass.

scholarly journals The Transcriptional Repressor ZEB Regulates p73 Expression at the Crossroad between Proliferation and Differentiation

2001 ◽  
Vol 21 (24) ◽  
pp. 8461-8470 ◽  
Author(s):  
Giulia Fontemaggi ◽  
Aymone Gurtner ◽  
Sabrina Strano ◽  
Yujiro Higashi ◽  
Ada Sacchi ◽  
...  
Keyword(s):  
Biological Activities ◽  
Ectopic Expression ◽  
Transcriptional Repressor ◽  
Dominant Negative ◽  
C2c12 Cells ◽  
Monocytic Differentiation ◽  
Hl60 Cells ◽  
Proliferation And Differentiation

ABSTRACT The newly discovered p73 gene encodes a nuclear protein that has high homology with p53. Furthermore, ectopic expression of p73 in p53+/+ and p53−/− cancer cells recapitulates some of the biological activities of p53 such as growth arrest, apoptosis, and differentiation. p73−/−-deficient mice exhibit severe defects in proper development of the central nervous system and pheromone sensory pathway. They also suffer from inflammation and infections. Here we studied the transcriptional regulation of p73 at the crossroad between proliferation and differentiation. p73 mRNA is undetectable in proliferating C2C12 cells and is expressed at very low levels in undifferentiated P19 and HL60 cells. Conversely, it is upregulated during muscle and neuronal differentiation as well as in response to tetradecanoyl phorbol acetate-induced monocytic differentiation of HL60 cells. We identified a 1-kb regulatory fragment located within the first intron of p73, which is positioned immediately upstream to the ATG codon of the second exon. This fragment exerts silencer activity on p73 as well as on heterologous promoters. The p73 intronic fragment contains six consensus binding sites for transcriptional repressor ZEB, which binds these sites in vitro and in vivo. Ectopic expression of dominant-negative ZEB (ZEB-DB) restores p73 expression in proliferating C2C12 and P19 cells. Thus, transcriptional repression of p73 expression by ZEB binding may contribute to the modulation of p73 expression during differentiation.

Increasing Wnt3a Signaling in Myeloma Cells Inhibits the Osteolytic Phenotype and Tumor Growth In Vivo through Regulation of the RANKL/OPG Axis in Osteoblasts and Indirectly Regulates Osteoclastogenesis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3506-3506
Author(s):  
Ya-Wei Qiang ◽  
Nathan Brown ◽  
Yu Chen ◽  
Shmuel Yaccoby ◽  
Bart Barlogie ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Wnt Signaling ◽  
Cell Line ◽  
Osteoclast Formation ◽  
C2c12 Cells ◽  
Myeloma Cells ◽  
Protein Levels ◽  
Canonical Wnt

Abstract We have demonstrated that canonical and non-canonical Wnt signaling occurs in myeloma cells (Qiang et al., 2005) and overexpression of Wnt3a in myeloma cells inhibits the osteolytic phenotype and also tumor growth in vivo (Qiang et al Blood, Abstract #3420, 2006). To further investigate the mechanisms that contribute to this process we have expanded our in vivo data by showing that while H929 cells stably expressing Wnt3a (H929/W3a) leads to reduced tumor growth in the in-vivo SCID-hu bone graft model compared with H929 vector alone transfected control cells (H929/EV), there was no significant difference in the subcutaneous growth of the two cell lines in SCID mice. Taken together these data suggests that alteration of the human bone marrow microenvironment is central to Wnt-mediated reduction in tumor growth in bone. We next employed an in-vitro co-culture model in which the mouse osteoprogenitor cell line, C2C12, and human osteoblast cell line, Saos-2 were co-cultured with either H929/Wnt3 or H929/EV cells. QPCR analysis demonstrated that osteoprotegerin (OPG) mRNA expression (relative OPG mRNA to GAPDH) in C2C12 cells co-cultured with H929/W3a was significantly elevated compared with H929/EV (mean±SD: 14.34±0.97 vs 8.43±0.16; P<0.001). ELISA analysis showed that OPG protein levels in the cell culture supernatant were also significantly higher (71.02 ± 6.178 vs 0 pg/ml; P<0.001). Similar results in OPG mRNA and protein levels were observed in Saos-2 cells co-cultured with H929/W3a relative to H929/EV. Furthermore, treatment of C2C12 cells with recombinant Wnt3a protein induced both OPG mRNA (48.1 ±1.2 vs 1.0±0.5; P<0.001) and protein levels (1767.03 ± 44.8 vs 1.11 ± 0.03 p< 0.0001) compared with vehicle alone. These results suggest that forced expression of a canonical Wnt ligand by MM cells might promote OPG transcription in osteoblast progenitors in-vivo. To further confirm the role of Wnt signaling in regulation of OPG and RANKL transcription, we produced C2C12 cells that stably express Dkk1. These clones showed a significant inhibition of Wnt3a induced OPG mRNA (22.2± 2.3 vs 1.7±0.35; p<0.001) and protein (73.3 ± 18.0 vs. 0 pg/ml; p<0.01) compared with vector control. In contrast, RANKL mRNA (5.1±0.9 vs 1.0± 0.5, p<0.01) and protein (9.3±3.8 vs. 0 pg/ml; p<0.01) were increased in Dkk1 expressing clones compared with control. Moreover, supernatant from C2C12 clones stably expressing a DN-beta-catenin (DNBC/C2C12) contained a significantly higher level of RANKL (17.3± 3.5 pg/ml vs. 0±0; P<0.001) and a dramatically lower level of OPG protein (0±0 vs. 431.186 pg/ml; P<0.001) compared with control. Finally, the numbers of multinuclear TRAP-positive osteoclasts were significantly more abundant in culture containing supernatant from DNBC/C2C12 than that from vector control, while Wnt3a exposure had no effect on osteoclast formation in-vitro. Taken together, these data suggest that Wnt ligand-mediated inhibition of myeloma cell growth, and inhibition of osteolytic lesions, in-vivo may result from upregulation of OPG and loss of RANKL in osteoblast progenitors, which subsequently diminishes osteoclast formation. Results of these studies provide new insights into mechanism by which Wnts may serve as an important indirect regulator of myeloma growth and osteoclast formation, and as such, targeting Wnt signaling may be an new therapeutic strategy for controlling myeloma growth and associated bone disease.

scholarly journals Modulation of rat preadipocyte adipose conversion by androgenic status: involvement of C/EBPs transcription factors

1999 ◽  
Vol 161 (1) ◽  
pp. 89-97 ◽  
Author(s):  
E Garcia ◽  
M Lacasa ◽  
B Agli ◽  
Y Giudicelli ◽  
D Lacasa
Keyword(s):  
Site Specific ◽  
Testosterone Treatment ◽  
Protein Levels ◽  
Fat Depots ◽  
Early Marker ◽  
Proliferation And Differentiation ◽  
Adipose Conversion ◽  
Testosterone Administration ◽  
Perirenal Fat

Androgenic status affects rat preadipocyte adipose conversion from two deep intra-abdominal (epididymal and perirenal) fat depots differently. The aim of this study was to establish whether these site-specific alterations of adipogenesis are related to altered expressions of the transcriptional factors regulating proliferation and differentiation of preadipocytes, c-myc and CCAAT/enhancer binding proteins (C/EBPs: C/EBPalpha and beta). The increased proliferation of epididymal and perirenal preadipocytes from castrated rats was not linked to variations in c-myc mRNA and protein levels. The expression of the early marker of adipogenesis, lipoprotein lipase (LPL), was decreased by androgenic deprivation in epididymal cells but remained insensitive to the androgenic status in perirenal preadipocytes. In contrast, LPL expression increased in subcutaneous preadipocytes from castrated rats, an effect which was partly corrected by testosterone treatment. Expression of C/EBPbeta was unaffected by androgenic status whatever the anatomical origin of the preadipocytes. In contrast, the mRNA and protein levels of C/EBPalpha were greatly decreased by androgenic deprivation in epididymal cells, an alteration which could not be corrected by in vivo testosterone administration. Altogether these results demonstrated that in preadipocytes androgenic deprivation affects site-specifically the expression of LPL, an early marker of adipogenesis and of C/EBPalpha, a master regulator of adipogenesis. These observations contribute to an explanation of why castration induces defective adipose conversion in rat epididymal preadipocytes specifically.

scholarly journals DAZL mediates a broad translational program regulating expansion and differentiation of spermatogonial progenitors

2020 ◽  
Author(s):  
Maria M. Mikedis ◽  
Yuting Fan ◽  
Peter K. Nicholls ◽  
Tsutomu Endo ◽  
Emily K. Jackson ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Coding ◽  
Protein Levels ◽  
Protein Coding Genes ◽  
Genetic Mouse Model ◽  
Proliferation And Differentiation ◽  
Gene Regulatory ◽  
Spermatogonial Proliferation

AbstractFertility across metazoa requires the germline-specific DAZ family of RNA-binding proteins. Here we examine whether DAZL directly regulates progenitor spermatogonia using a conditional genetic mouse model and in vivo biochemical approaches combined with chemical synchronization of spermatogenesis. We find that the absence of Dazl impairs both expansion and differentiation of the spermatogonial progenitor population. In undifferentiated spermatogonia, DAZL binds the 3’ UTRs of ∼2,500 protein-coding genes. Some targets are known regulators of spermatogonial proliferation and differentiation while others are broadly expressed, dosage-sensitive factors that control transcription and RNA metabolism. DAZL binds 3’ UTR sites conserved across vertebrates at a UGUU(U/A) motif. By assessing ribosome occupancy in undifferentiated spermatogonia, we find that DAZL increases translation of its targets. In total, DAZL orchestrates a broad translational program that amplifies protein levels of key spermatogonial and gene regulatory factors to promote the expansion and differentiation of progenitor spermatogonia.

scholarly journals Satellite cells and their regulation in livestock

2020 ◽  
Vol 98 (5) ◽  
Author(s):  
Madison L Gonzalez ◽  
Nicolas I Busse ◽  
Christy M Waits ◽  
Sally E Johnson
Keyword(s):  
Growth Factor ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Intracellular Signaling ◽  
Transforming Growth Factor ◽  
Myogenic Differentiation ◽  
Cell Activity ◽  
Large Animal ◽  
Quiescent State ◽  
Proliferation And Differentiation

Abstract Satellite cells are the myogenic stem and progenitor population found in skeletal muscle. These cells typically reside in a quiescent state until called upon to support repair, regeneration, or muscle growth. The activities of satellite cells are orchestrated by systemic hormones, autocrine and paracrine growth factors, and the composition of the basal lamina of the muscle fiber. Several key intracellular signaling events are initiated in response to changes in the local environment causing exit from quiescence, proliferation, and differentiation. Signals emanating from Notch, wingless-type mouse mammary tumor virus integration site family members, and transforming growth factor-β proteins mediate the reversible exit from growth 0 phase while those initiated by members of the fibroblast growth factor and insulin-like growth factor families direct proliferation and differentiation. Many of these pathways impinge upon the myogenic regulatory factors (MRF), myogenic factor 5, myogenic differentiation factor D, myogenin and MRF4, and the lineage determinate, Paired box 7, to alter transcription and subsequent satellite cell decisions. In the recent past, insight into mouse transgenic models has led to a firm understanding of regulatory events that control satellite cell metabolism and myogenesis. Many of these niche-regulated functions offer subtle differences from their counterparts in livestock pointing to the existence of species-specific controls. The purpose of this review is to examine the mechanisms that mediate large animal satellite cell activity and their relationship to those present in rodents.

scholarly journals Differential regulation of the retinoblastoma family of proteins during cell proliferation and differentiation

1998 ◽  
Vol 333 (3) ◽  
pp. 645-654 ◽  
Author(s):  
Judit GARRIGA ◽  
Ana LIMÓN ◽  
Xavier MAYOL ◽  
Sushil G. RANE ◽  
Jeffrey H. ALBRECHT ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Protein Expression ◽  
Cultured Cells ◽  
Protein Levels ◽  
Pocket Protein ◽  
Cell Proliferation And Differentiation ◽  
Mouse Tissues ◽  
Proliferation And Differentiation

In the present study we have analysed the regulation of pocket protein expression and post-transcriptional modifications on cell proliferation and differentiation, both in vivo and in vitro. There are marked changes in pocket protein levels during these transitions, the most striking differences being observed between p130 and p107. The mechanisms responsible for regulating pocket protein levels seem to be dependent on both cell type and pocket protein, in addition to their dependence on the cell growth status. Changes in retinoblastoma protein and p107 levels are independent of their state of phosphorylation. However, whereas p130 phosphorylation to forms characteristic of quiescent/differentiated cells results in the accumulation of p130 protein, phosphorylation of p130 to one or more forms characteristic of cycling cells is accompanied by down-regulation of its protein levels. We also show here that the phosphorylation status and protein levels of p130 and p107 are regulated in vivo as in cultured cells. In vivo, changes in p130 forms are correlated with changes in E2F complexes. Moreover, the modulation of p130 and p107 status during cell differentiation in vitro is consistent with the patterns of protein expression and phosphorylation status found in mouse tissues. Thus in addition to the direct disruption of pocket protein/E2F complexes induced by cyclin/cyclin-dependent kinase, the results we report here indicate that the differential modulation of pocket protein levels constitutes a major mechanism that regulates the pool of each pocket protein that is accessible to E2F and/or other transcription factors.

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