scholarly journals Age and Sex-Dependent ADNP Regulation of Muscle Gene Expression Is Correlated with Motor Behavior: Possible Feedback Mechanism with PACAP

2020 ◽  
Vol 21 (18) ◽  
pp. 6715 ◽  
Author(s):  
Oxana Kapitansky ◽  
Shlomo Sragovich ◽  
Iman Jaljuli ◽  
Adva Hadar ◽  
Eliezer Giladi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscle Development ◽  
Motor Behavior ◽  
Expression Patterns ◽  
Feedback Mechanism ◽  
Bladder Function ◽  
Drug Candidate ◽  
Specific Gene ◽  
Muscle Gene Expression ◽  
Muscle Gene

The activity-dependent neuroprotective protein (ADNP), a double-edged sword, sex-dependently regulates multiple genes and was previously associated with the control of early muscle development and aging. Here we aimed to decipher the involvement of ADNP in versatile muscle gene expression patterns in correlation with motor function throughout life. Using quantitative RT-PCR we showed that Adnp+/− heterozygous deficiency in mice resulted in aberrant gastrocnemius (GC) muscle, tongue and bladder gene expression, which was corrected by the Adnp snippet, drug candidate, NAP (CP201). A significant sexual dichotomy was discovered, coupled to muscle and age-specific gene regulation. As such, Adnp was shown to regulate myosin light chain (Myl) in the gastrocnemius (GC) muscle, the language acquisition gene forkhead box protein P2 (Foxp2) in the tongue and the pituitary-adenylate cyclase activating polypeptide (PACAP) receptor PAC1 mRNA (Adcyap1r1) in the bladder, with PACAP linked to bladder function. A tight age regulation was observed, coupled to an extensive correlation to muscle function (gait analysis), placing ADNP as a muscle-regulating gene/protein.

scholarly journals Skeletal muscle gene expression after myostatin knockout in mature mice

2009 ◽  
Vol 38 (3) ◽  
pp. 342-350 ◽  
Author(s):  
Stephen Welle ◽  
Andrew Cardillo ◽  
Michelle Zanche ◽  
Rabi Tawil
Keyword(s):  
Gene Expression ◽  
Muscle Development ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Muscle Gene Expression ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Muscle Gene ◽  
Or Genes ◽  
And Control

There is much interest in developing anti-myostatin agents to reverse or prevent muscle atrophy in adults, so it is important to characterize the effects of reducing myostatin activity after normal muscle development. For assessment of the effect of loss of myostatin signaling on gene expression in muscle, RNA from mice with postdevelopmental myostatin knockout was analyzed with oligonucleotide microarrays. Myostatin was undetectable in muscle within 2 wk after Cre recombinase activation in 4-month-old male mice with floxed myostatin genes. Three months after myostatin depletion, muscle mass had increased 26% (vs. 2% after induction of Cre activity in mice with normal myostatin genes), at which time the expression of several hundred genes differed in knockout and control mice at nominal P < 0.01. In contrast to previously reported effects of constitutive myostatin knockout, postdevelopmental knockout did not downregulate expression of genes encoding slow isoforms of contractile proteins or genes encoding proteins involved in energy metabolism. Several collagen genes were expressed at 20–50% lower levels in the myostatin-deficient muscles, which had ∼25% less collagen than normal muscles as reflected by hydroxyproline content. Most of the other genes affected by myostatin depletion have not been previously linked to myostatin signaling. Gene set enrichment analysis suggested that Smads are not the only transcription factors with reduced activity after myostatin depletion. These data reinforce other evidence that myostatin regulates collagen production in muscle and demonstrate that many of the previously reported effects of constitutive myostatin deficiency do not occur when myostatin is knocked out in mature muscles.

scholarly journals Muscle Gene Expression Patterns in Human Rotator Cuff Pathology

2014 ◽  
Vol 96 (18) ◽  
pp. 1558-1565 ◽  
Author(s):  
Alexander Choo ◽  
Meagan McCarthy ◽  
Rajeswari Pichika ◽  
Eugene J Sato ◽  
Richard L Lieber ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rotator Cuff ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
Human Rotator Cuff

Tumor necrosis factor inhibits human myogenesis in vitro

1988 ◽  
Vol 8 (6) ◽  
pp. 2295-2301
Author(s):  
S C Miller ◽  
H Ito ◽  
H M Blau ◽  
F M Torti
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Myoblast Differentiation ◽  
Specific Gene ◽  
Necrosis Factor Alpha ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
Necrosis Factor

We examined the effects of human recombinant tumor necrosis factor-alpha (TNF) on human primary myoblasts. When added to proliferating myoblasts, TNF inhibited the expression of alpha-cardiac actin, a muscle-specific gene whose expression is observed at low levels in human myoblasts. TNF also inhibited muscle differentiation as measured by several parameters, including cell fusion and the expression of other muscle-specific genes, such as alpha-skeletal actin and myosin heavy chain. Muscle cells were sensitive to TNF in a narrow temporal window of differentiation. Northern (RNA) blot and immunofluorescence analyses revealed that human muscle gene expression became unresponsive to TNF coincident with myoblast differentiation. When TNF was added to differentiated myotubes, there was no effect on muscle gene expression. In contrast, TNF-inducible mRNAs such as interferon beta-2 still responded, suggesting that the signal mediated by TNF binding to its receptor had no effect on muscle-specific genes after differentiation.

scholarly journals Influence of age, sex, and strength training on human muscle gene expression determined by microarray

2002 ◽  
Vol 10 (3) ◽  
pp. 181-190 ◽  
Author(s):  
Stephen M. Roth ◽  
Robert E. Ferrell ◽  
David G. Peters ◽  
E. Jeffrey Metter ◽  
Ben F. Hurley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Strength Training ◽  
Differential Expression ◽  
Quantitative Pcr ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Vastus Lateralis Muscle ◽  
Men And Women ◽  
Muscle Gene Expression ◽  
Muscle Gene

The purpose of this study was to determine the influence of age, sex, and strength training (ST) on large-scale gene expression patterns in vastus lateralis muscle biopsies using high-density cDNA microarrays and quantitative PCR. Muscle samples from sedentary young (20–30 yr) and older (65–75 yr) men and women (5 per group) were obtained before and after a 9-wk unilateral heavy resistance ST program. RNA was hybridized to cDNA filter microarrays representing ∼4,000 known human genes and comparisons were made among arrays to determine differential gene expression as a result of age and sex differences, and/or response to ST. Sex had the strongest influence on muscle gene expression, with differential expression (>1.7-fold) observed for ∼200 genes between men and women (∼75% with higher expression in men). Age contributed to differential expression as well, as ∼50 genes were identified as differentially expressed (>1.7-fold) in relation to age, representing structural, metabolic, and regulatory gene classes. Sixty-nine genes were identified as being differentially expressed (>1.7-fold) in all groups in response to ST, and the majority of these were downregulated. Quantitative PCR was employed to validate expression levels for caldesmon, SWI/SNF (BAF60b), and four-and-a-half LIM domains 1. These significant differences suggest that in the analysis of skeletal muscle gene expression issues of sex, age, and habitual physical activity must be addressed, with sex being the most critical variable.

scholarly journals Tumor necrosis factor inhibits human myogenesis in vitro.

1988 ◽  
Vol 8 (6) ◽  
pp. 2295-2301 ◽  
Author(s):  
S C Miller ◽  
H Ito ◽  
H M Blau ◽  
F M Torti
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Myoblast Differentiation ◽  
Specific Gene ◽  
Necrosis Factor Alpha ◽  
Muscle Gene Expression ◽  
Muscle Gene ◽  
Necrosis Factor

We examined the effects of human recombinant tumor necrosis factor-alpha (TNF) on human primary myoblasts. When added to proliferating myoblasts, TNF inhibited the expression of alpha-cardiac actin, a muscle-specific gene whose expression is observed at low levels in human myoblasts. TNF also inhibited muscle differentiation as measured by several parameters, including cell fusion and the expression of other muscle-specific genes, such as alpha-skeletal actin and myosin heavy chain. Muscle cells were sensitive to TNF in a narrow temporal window of differentiation. Northern (RNA) blot and immunofluorescence analyses revealed that human muscle gene expression became unresponsive to TNF coincident with myoblast differentiation. When TNF was added to differentiated myotubes, there was no effect on muscle gene expression. In contrast, TNF-inducible mRNAs such as interferon beta-2 still responded, suggesting that the signal mediated by TNF binding to its receptor had no effect on muscle-specific genes after differentiation.

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.

The Caenorhabditis elegans NK-2 homeobox gene ceh-22 activates pharyngeal muscle gene expression in combination with pha-1 and is required for normal pharyngeal development

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 3965-3973 ◽  
Author(s):  
P.G. Okkema ◽  
E. Ha ◽  
C. Haun ◽  
W. Chen ◽  
A. Fire
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Muscle Development ◽  
Synergistic Effects ◽  
Chain Gene ◽  
Loss Of Function ◽  
Pharyngeal Muscle ◽  
Muscle Gene Expression ◽  
Pharyngeal Muscles ◽  
Muscle Gene

Pharyngeal muscle development in the nematode Caenorhabditis elegans appears to share similarities with cardiac muscle development in other species. We have previously described CEH-22, an NK-2 class homeodomain transcription factor similar to Drosophila tinman and vertebrate Nkx2-5, which is expressed exclusively in the pharyngeal muscles. In vitro, CEH-22 binds the enhancer from myo-2, a pharyngeal muscle-specific myosin heavy chain gene. In this paper, we examine the role CEH-22 plays in pharyngeal muscle development and gene activation by (a) ectopically expressing ceh-22 in transgenic C. elegans and (b) examining the phenotype of a ceh-22 loss-of-function mutant. These experiments indicate that CEH-22 is an activator of myo-2 expression and that it is required for normal pharyngeal muscle development. However, ceh-22 is necessary for neither formation of the pharyngeal muscles, nor for myo-2 expression. Our data suggest parallel and potentially compensating pathways contribute to pharyngeal muscle differentiation. We also examine the relationship between ceh-22 and the pharyngeal organ-specific differentiation gene pha-1. Mutations in ceh-22 and pha-1 have strongly synergistic effects on pharyngeal muscle gene expression; in addition, a pha-1 mutation enhances the lethal phenotype caused by a mutation in ceh-22. Wild-type pha-1 is not required for the onset of ceh-22 expression but it appears necessary for maintained expression of ceh-22.

scholarly journals Heterogeneous muscle gene expression patterns in patients with massive rotator cuff tears

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0190439 ◽  
Author(s):  
Michael C. Gibbons ◽  
Kathleen M. Fisch ◽  
Rajeswari Pichika ◽  
Timothy Cheng ◽  
Adam J. Engler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rotator Cuff ◽  
Expression Patterns ◽  
Rotator Cuff Tears ◽  
Gene Expression Patterns ◽  
Muscle Gene Expression ◽  
Massive Rotator Cuff Tears ◽  
Muscle Gene
Sign in / Sign up

Export Citation Format

Share Document