scholarly journals Time course of changes in markers of myogenesis in overloaded rat skeletal muscles

1999 ◽  
Vol 87 (5) ◽  
pp. 1705-1712 ◽  
Author(s):  
Gregory R. Adams ◽  
Fadia Haddad ◽  
Kenneth M. Baldwin
Keyword(s):  
Cyclin D1 ◽  
Time Course ◽  
Cellular Proliferation ◽  
Early Time ◽  
Time Points ◽  
Muscle Gene Expression ◽  
Igf I ◽  
Cellular Markers ◽  
Compensatory Muscle Hypertrophy ◽  
Muscle Gene

During the process of compensatory muscle hypertrophy, satellite cells are thought to proliferate, differentiate, and then fuse with existing myofibers. We hypothesized that early in this process changes occur in the expression of cellular markers indicative of the onset of myogenic processes. The plantaris muscles of rats were overloaded via the unilateral ablation of synergists. Groups of rats were killed at time points from 6 h to 12 days. Changes in muscle gene expression (mRNA) of cyclin D1, p21, myogenin, MyoD, and insulin-like growth factor I (IGF-I, mRNA and peptide) were measured. Cyclin D1 (a cell cycle marker) was increased after 24 h of overloading and corresponded with changes in muscle DNA content. In contrast, p21 and myogenin, markers of cellular differentiation, were increased after just 12 h. Muscle IGF-I peptide levels were also increased at early time points. The results of this study indicate that myogenic processes are activated in response to increased loading at very early time points (e.g., 12 h) and that IGF-I may be modulating this response. Furthermore, these findings suggest that some cells may have been differentiating very early in the adaptation process before events leading to cellular proliferation have been initiated.

Switches in cardiac muscle gene expression as a result of pressure and volume overload

1992 ◽  
Vol 262 (3) ◽  
pp. R364-R369 ◽  
Author(s):  
K. Schwartz ◽  
K. R. Boheler ◽  
D. de la Bastie ◽  
A. M. Lompre ◽  
J. J. Mercadier
Keyword(s):  
Time Course ◽  
Volume Overload ◽  
Early Time ◽  
High Plasma ◽  
Endocrine Function ◽  
Contractile Element ◽  
Muscle Gene Expression ◽  
Atpase Gene ◽  
Hemodynamic Overload ◽  
Muscle Gene

In the mammalian heart, the expression of genes encoding proteins responsible for contraction, relaxation, and endocrine function changes in hypertrophy resulting from hemodynamic overload. Different mechanisms are involved in this mechanogenic transduction, including 1) differential expression of myosin and actin multigene families, which may account for the decreased velocity of contractile element shortening in hypertrophied heart, 2) nonactivation of the sarcoplasmic reticulum Ca(2+)-ATPase gene, which may explain the increased duration of isometric relaxation, and finally 3) activation in the ventricle of the atrial natriuretic factor gene that is responsible in part for the high plasma levels of this peptide. It is increasingly apparent that these changes are independently regulated, but little is known about the mechanisms underlying this regulation. Preliminary results indicate that it is now possible to analyze the early time course or transcription for each gene after the imposition of hemodynamic overload. This should significantly enhance our understanding of the regulatory mechanisms involved in the phenoconversions of the hemodynamically overloaded heart.

F-actin serves as a template for cytokeratin organization in cell free extracts

2002 ◽  
Vol 115 (7) ◽  
pp. 1373-1382 ◽  
Author(s):  
Kari L. Weber ◽  
William M. Bement
Keyword(s):  
Time Course ◽  
Early Time ◽  
Dynamic Imaging ◽  
Actin Network ◽  
Intact Cells ◽  
Time Points ◽  
Egg Extracts ◽  
Actin Cables

The microtubule, F-actin, and intermediate filament systems are often studied as isolated systems, yet the three display mutual interdependence in living cells. To overcome limitations inherent in analysis of polymer-polymer interactions in intact cells, associations between these systems were assessed in Xenopus egg extracts. In both fixed and unfixed extract preparations, cytokeratin associated with F-actin cables that spontaneously assembled in the extracts. Time-course experiments revealed that at early time points cytokeratin cables were invariably associated with F-actin cables,while at later time points they could be found without associated F-actin. In extract samples where F-actin assembly was prevented, cytokeratin formed unorganized aggregates rather than cables. Dynamic imaging revealed transport of cytokeratin by moving F-actin as well as examples of cytokeratin release from F-actin. Experimental alteration of F-actin network organization by addition of α-actinin resulted in a corresponding change in the organization of the cytokeratin network. Finally, pharmacological disruption of the F-actin network in intact, activated eggs disrupted the normal pattern of cytokeratin assembly. These results provide direct evidence for an association between F-actin and cytokeratin in vitro and in vivo, and indicate that this interaction is necessary for proper cytokeratin assembly after transition into the first mitotic interphase of Xenopus.

Distribution and Elimination of [2-14C]Amino-3, 8-Dimethylimidazo [4, 5-f] quinoxaline in Mice. Analysis by Whole Animal Autoradiography

1991 ◽  
Vol 10 (5) ◽  
pp. 337-345 ◽  
Author(s):  
N.J. Gooderham ◽  
A. Soames ◽  
J.C. Rice ◽  
A.R. Boobis ◽  
D.S. Davies
Keyword(s):  
Central Nervous System ◽  
Time Course ◽  
Liver Enzymes ◽  
Early Time ◽  
Body Tissue ◽  
Significant Extent ◽  
Time Points ◽  
The Central Nervous System ◽  
Extrahepatic Tissues ◽  
Good Agreement

1 2-Amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx) is a potent bacterial pro-mutagen and carcinogen, formed when beef is cooked. In mammals, MeIQx is metabolized and activated by liver enzymes, but induces tumours in both hepatic and extrahepatic tissues. 2 Intravenous administration of [14C]MeIQx and whole animal autoradiography has been employed to examine the diposition of MeIQx. Within 10 min, radiolabel was distributed throughout body tissue. Liver levels of radioactivity rapidly rose and remained elevated in comparison to other tissues, throughout the period of study (4 d). 3 At early time points radioactivity accumulated in the stomach, kidney and salivary glands then later in the intestine. Radioactivity was rapidly eliminated from the majority of tissues although did persist in liver and intestines throughout the duration of the study, probably due to covalently bound material. No radioactivity could be detected in the central nervous system, thus neither MeIQx nor its metabolites cross the blood—brain barrier to any significant extent. 4 The rapid elimination of radioactivity from the tissues is in good agreement with the time course of excretion of MeIQx. Irrespective of the route of administration (i.v., i.p., p.o.), a substantial proportion of the labelled material is excreted within 24 h and is present in both urine and faeces in similar quantities. 5 Thus MeIQx is extensively bioavailable, is distributed throughout body tissue and, although the majority is quickly cleared, some remains bound to liver and intestine.

Temporal alterations in protein signaling cascades during recovery from muscle atrophy

2003 ◽  
Vol 285 (2) ◽  
pp. C391-C398 ◽  
Author(s):  
Thomas E. Childs ◽  
Espen E. Spangenburg ◽  
Dharmesh R. Vyas ◽  
Frank W. Booth
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Time Course ◽  
Glycogen Synthase ◽  
Early Time ◽  
Protein Translation ◽  
Skeletal Muscle Atrophy ◽  
Time Points

Currently, the repertoire of cellular and molecular pathways that control skeletal muscle atrophy and hypertrophy are not well defined. It is possible that intracellular regulatory signaling pathways are active at different times during the muscle hypertrophy process. The hypothesis of the given experiments was that cellular signals related to protein translation would be active at early time points of skeletal muscle regrowth, whereas transcriptional signals would be active at later time points of skeletal muscle regrowth. The phosphorylation status of p38 MAPK and JNK increased at the end of limb immobilization but returned to control values at recovery day 3. Transient increases in phosphorylation and in protein concentration occurred during recovery of soleus muscle mass. Phosphorylation of Akt, p70S6k, and signal transducer and activator of transcription 3 (STAT3) peaked on recovery day 3 compared with day 0. Glycogen synthase kinase (GSK)-3β phosphorylation was increased on the sixth and fifteenth recovery day. In addition, transient peaks in seven protein concentrations occurred at different times of recovery: STAT3, calcineurin A (CaNA), CaNB, and β4E-BP1 protein concentrations peaked on the third recovery day; p70S6k, STAT3, Akt, and GSK3-β peaked on the sixth recovery day; and GSK3-β peaked on the fifteenth recovery day. The apexes of STAT3 and GSK3-β protein concentrations remained elevated for two recovery time points. Thus the time course of increase in molecules of signaling pathways differed as the young rat soleus muscle regrew from an atrophied state.

scholarly journals Expression of muscle genes in heterokaryons depends on gene dosage.

1986 ◽  
Vol 102 (1) ◽  
pp. 124-130 ◽  
Author(s):  
G K Pavlath ◽  
H M Blau
Keyword(s):  
Gene Expression ◽  
Time Course ◽  
Gene Dosage ◽  
Cell Types ◽  
Threshold Concentration ◽  
Specific Gene ◽  
Mouse Muscle ◽  
Muscle Gene Expression ◽  
Muscle Genes ◽  
Muscle Gene

We report that gene dosage, or the ratio of nuclei from two cell types fused to form a heterokaryon, affects the time course of differentiation-specific gene expression. The rate of appearance of the human muscle antigen, 5.1H11, is significantly faster in heterokaryons with equal or near-equal numbers of mouse muscle and human fibroblast nuclei than in heterokaryons with increased numbers of nuclei from either cell type. By 4 d after fusion, a high frequency of gene expression is evident at all ratios and greater than 75% of heterokaryons express the antigen even when the nonmuscle nuclei greatly outnumber the muscle nuclei. The kinetic differences observed with different nuclear ratios suggest that the concentration of putative trans-acting factors significantly influences the rate of muscle gene expression: a threshold concentration is necessary, but an excess may be inhibitory.

scholarly journals Genome-wide kinetics of DNA excision repair in relation to chromatin state and mutagenesis

2016 ◽  
Vol 113 (15) ◽  
pp. E2124-E2133 ◽  
Author(s):  
Sheera Adar ◽  
Jinchuan Hu ◽  
Jason D. Lieb ◽  
Aziz Sancar
Keyword(s):  
Time Course ◽  
Excision Repair ◽  
Early Time ◽  
Chromatin State ◽  
Open Chromatin ◽  
Late Time ◽  
Normal Human Skin ◽  
Time Points ◽  
Dna Excision Repair ◽  
Genome Wide

We recently developed a high-resolution genome-wide assay for mapping DNA excision repair named eXcision Repair-sequencing (XR-seq) and have now used XR-seq to determine which regions of the genome are subject to repair very soon after UV exposure and which regions are repaired later. Over a time course, we measured repair of the UV-induced damage of cyclobutane pyrimidine dimers (CPDs) (at 1, 4, 8, 16, 24, and 48 h) and (6-4)pyrimidine-pyrimidone photoproducts [(6-4)PPs] (at 5 and 20 min and 1, 2, and 4 h) in normal human skin fibroblasts. Each type of damage has distinct repair kinetics. The (6-4)PPs are detected as early as 5 min after UV treatment, with the bulk of repair completed by 4 h. Repair of CPDs, which we previously showed is intimately coupled to transcription, is slower and in certain regions persists even 2 d after UV irradiation. We compared our results to the Encyclopedia of DNA Elements data regarding histone modifications, chromatin state, and transcription. For both damage types, and for both transcription-coupled and general excision repair, the earliest repair occurred preferentially in active and open chromatin states. Conversely, repair in regions classified as “heterochromatic” and “repressed” was relatively low at early time points, with repair persisting into the late time points. Damage that remains during DNA replication increases the risk for mutagenesis. Indeed, late-repaired regions are associated with a higher level of cancer-linked mutations. In summary, we show that XR-seq is a powerful approach for studying relationships among chromatin state, DNA repair, genome stability, mutagenesis, and carcinogenesis.

Globin synthesis in heterokaryons formed between chick erythrocytes and human K562 cells or rat L6 myoblasts

1984 ◽  
Vol 66 (1) ◽  
pp. 309-319
Author(s):  
G. Lanfranchi ◽  
S. Linder ◽  
N.R. Ringertz
Keyword(s):  
Time Course ◽  
Early Time ◽  
K562 Cells ◽  
Late Time ◽  
Globin Chain ◽  
Time Points ◽  
Erythroleukemia Cells ◽  
Globin Synthesis ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Chick globin synthesis was studied in heterokaryons formed between chick erythrocytes and human K562 erythroleukemia cells or rat L6J1 myoblasts. It was found that chick globin synthesis was activated after fusion of definitive (17 to 19-day) chick erythrocytes obtained from 17 to 19-day embryos with K562 cells. Chick globins appeared to be of the adult alpha A, alpha D and beta types, whereas no embryonic globin synthesis could be detected. The pattern and time-course of globin synthesis was investigated after fusion of 4 to 5-day embryonic erythrocytes with rat L6J1 myoblasts. The level of globin synthesis was high at early time points but then decreased. Globin synthesis, however, was still detectable at 9 days in these heterokaryons. Chick alpha A, alpha D and epsilon-globin chain synthesis was observed both at early and late time points after fusion.

Time course of collagen and decorin changes in rat cardiac and skeletal muscle post-MI

2001 ◽  
Vol 281 (4) ◽  
pp. H1816-H1822 ◽  
Author(s):  
Scott D. Zimmerman ◽  
D. Paul Thomas ◽  
Sandra G. Velleman ◽  
Xia Li ◽  
Thomas R. Hansen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Time Course ◽  
Early Time ◽  
Cross Linking ◽  
Type I ◽  
Collagen Concentration ◽  
Ecm Remodeling ◽  
Time Points ◽  
Type Iii ◽  
Type Iii Procollagen

We examined the temporal relationship between messages (type I and type III mRNAs) for the principal fibrillar procollagens and subsequent collagen accretion, cross-linking, and decorin expression in the left ventricle (LV) postmyocardial infarction (post-MI). We sought to determine 1) what role the proteoglycan decorin plays in extracellular matrix (ECM) remodeling known to take place as a consequence of MI and 2) the extent skeletal muscle ECM is altered early post-MI. Therefore, after surgically induced production of small- to moderate-sized infarcts (∼20% of LV mass), extent and time course of ECM remodeling was evaluated in remaining viable LV free wall and in slow- [soleus (SOL)] and fast-twitch [gastrocnemius (GAST)] skeletal muscles. Decorin, collagen, and hydroxylysylpyridinium cross-link concentrations and α1(I) (type I) and α1(III) (type III) procollagen mRNAs were measured in LVs from noninfarcted controls and at 72 h, 1, 2, 5, and 13 wk post-MI. These same data were collected in SOL and GAST muscles at all time points except 13 wk. Type I procollagen mRNA increased at both 72-h and 1-wk time points in LVs. Type III procollagen mRNA was elevated at 1 wk, returning to baseline by 2 wk post-MI. Collagen concentration was significantly increased by 1 wk, more than doubled by 5 wk, and was elevated 129% by 13 wk in the remaining viable LV. LV decorin expression was unaltered at early time points, but increased 38% at 5 wk post-MI and doubled by 13 wk post-MI. In skeletal muscle, procollagen mRNAs were transiently altered in SOL and GAST muscles without any demonstrable effect on the measured ECM parameters. This study reports, for the first time, the upregulation time course of decorin and its relationship to increased HP cross-linking and accumulation of collagen in viable myocardium post-MI.

scholarly journals Time-dependent mediators of HPA axis activation following live Escherichia coli

2011 ◽  
Vol 301 (6) ◽  
pp. R1648-R1657 ◽  
Author(s):  
Z. R. Zimomra ◽  
V. M. Porterfield ◽  
R. M. Camp ◽  
J. D. Johnson
Keyword(s):  
Escherichia Coli ◽  
Inflammatory Cytokines ◽  
Hpa Axis ◽  
Time Course ◽  
Early Time ◽  
Plasma Corticosterone ◽  
Sprague Dawley ◽  
E Coli ◽  
Time Points ◽  
Early Rise

The hypothalamus-pituitary-adrenal (HPA) axis is activated during an immune challenge to liberate energy and modulate immune responses via feedback and regulatory mechanisms. Inflammatory cytokines and prostaglandins are known contributors to HPA activation; however, most previous studies only looked at specific time points following LPS administration. Since whole bacteria have different immune stimulatory properties compared with LPS, the aim of the present studies was to determine whether different immune products contribute to HPA activation at different times following live Escherichia coli challenge. Sprague-Dawley rats were injected intraperitoneally with E. coli (2.5 × 107 CFU) and a time course of circulating corticosterone, ACTH, inflammatory cytokines, and PGE2 was developed. Plasma corticosterone peaked 0.5 h after E. coli and steadily returned to baseline by 4 h. Plasma PGE2 correlated with the early rise in plasma corticosterone, whereas inflammatory cytokines were not detected until 2 h. Pretreatment with indomethacin, a nonselective cyclooxygenase inhibitor, completely blocked the early rise in plasma corticosterone, but not at 2 h, whereas pretreatment with IL-6 antibodies had no effect on the early rise in corticosterone but attenuated corticosterone at 2 h. Interestingly, indomethacin pretreatment did not completely block the early rise in corticosterone following a higher concentration of E. coli (2.5 × 108 CFU). Further studies revealed that only animals receiving indomethacin prior to E. coli displayed elevated plasma and liver cytokines at early time points (0.5 and 1 h), suggesting prostaglandins suppress early inflammatory cytokine production. Overall, these data indicate prostaglandins largely mediate the early rise in plasma corticosterone, while inflammatory cytokines contribute to maintaining levels of corticosterone at later time points.

scholarly journals Cyclin-mediated inhibition of muscle gene expression via a mechanism that is independent of pRB hyperphosphorylation.

1996 ◽  
Vol 16 (12) ◽  
pp. 7043-7053 ◽  
Author(s):  
S X Skapek ◽  
J Rhee ◽  
P S Kim ◽  
B G Novitch ◽  
A B Lassar
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cyclin D1 ◽  
Ectopic Expression ◽  
Muscle Differentiation ◽  
Skeletal Muscle Differentiation ◽  
Muscle Gene Expression ◽  
Cell Biol ◽  
Cdk Phosphorylation ◽  
Muscle Gene

It was recently demonstrated that ectopic expression of cyclin D1 inhibits skeletal muscle differentiation and, conversely, that expression of cyclin-dependent kinase (cdk) inhibitors facilitates activation of this differentiation program (S. S. Rao, C. Chu, and D. S. Kohtz, Mol. Cell. Biol. 14:5259-5267, 1994; S. S. Rao and D. S. Kohtz, J. Biol. Chem. 270:4093-4100, 1995; S. X. Skapek, J. Rhee, D. B. Spicer, and A. B. Lassar, Science 267:1022-1024, 1995). Here we demonstrate that cyclin D1 inhibits muscle gene expression without affecting MyoD DNA binding activity. Ectopic expression of cyclin D1 inhibits muscle gene activation by both MyoD and myogenin, including a mutated form of myogenin in which two potential inhibitory cdk phosphorylation sites are absent. Because the retinoblastoma gene product, pRB, is a known target for cyclin D1-cdk phosphorylation, we determined whether cyclin D1-mediated inhibition of myogenesis was due to hyperphosphorylation of pRB. In pRB-deficient fibroblasts, the ability of MyoD to activate the expression of muscle-specific genes requires coexpression of ectopic pRB (B. G. Novitch, G. J. Mulligan, T. Jacks, and A. B. Lassar, J. Cell Biol., 135:441-456, 1996). In these cells, the expression of cyclins A and E can lead to pRB hyperphosphorylation and can inhibit muscle gene expression. The negative effects of cyclins A or E on muscle gene expression are, however, reversed by the presence of a mutated form of pRB which cannot be hyperphosphorylated. In contrast, cyclin D1 can inhibit muscle gene expression in the presence of the nonhyperphosphorylatable form of pRB. On the basis of these results we propose that G1 cyclin-cdk activity blocks the initiation of skeletal muscle differentiation by two distinct mechanisms: one that is dependent on pRB hyperphosphorylation and one that is independent of pRB hyperphosphorylation.

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