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Papers by Frank Booth

American Journal of Physiology Cell Physiology, Jul 1, 1999

Components of signaling pathways for mechanotransduction during load-induced enlargement of skele... more Components of signaling pathways for mechanotransduction during load-induced enlargement of skeletal muscle have not been completely defined. We hypothesized that loading of skeletal muscle would result in an adaptive increase in the expression of two focal adhesion complex (FAC)-related proteins, focal adhesion kinase (FAK) and paxillin, as well as increased FAK activity. FAK protein was immunolocalized to the sarcolemmal region of rooster anterior latissimus dorsi (ALD) myofibers in the middle of the ALD muscle. FAK (77 and 81%) and paxillin (206 and 202%) protein concentrations per unit of total protein in Western blots increased significantly after 1.5 and 7 days, but not after 13 days, of stretch-induced hypertrophy-hyperplasia of the ALD muscle. FAK autokinase activity in immunoprecipitates was increased after 1.5, 7, and 13 days in stretched ALD muscles. To determine whether increased FAK and paxillin protein concentrations are associated with hypertrophy and/or new fiber formation, two additional experiments were performed. First, during formation of primary chicken myotubes (a model of new fiber formation), FAK protein concentration (63%), FAK activity (157%), and paxillin protein concentration (97%) increased compared with myoblasts. Second, FAK (112% and 611%) and paxillin (87% and 431%) protein concentrations per unit of total protein in the soleus muscle increased at 1 and 8 days after surgical ablation of the synergistic gastrocnemius muscle (a model of hypertrophy without hyperplasia). Thus increases in components of the FAC occur in hypertrophying muscle of animals and in newly formed muscle fibers in culture. Furthermore, increased FAK activity suggests a possible convergence of signaling at the FAC in load-induced growth of skeletal muscle.

The Faseb Journal, Apr 1, 2009

J Appl Physiol, 2006

Previously, inducing inactivity for 53 hours after 21 days of voluntary running resulted in a 25%... more Previously, inducing inactivity for 53 hours after 21 days of voluntary running resulted in a 25% and 48% increase in epididymal and omental fat pad weights, respectively, while rats continued to eat more than a group that never had access to a running wheel. We wanted to test the hypothesis that inactivity, independent of excessive caloric intake, could induce an increase in fat-pad mass. 21-day old rats were given access to voluntary running wheels for 42-43 days so that they were running ~9 km/day in the last week of running, after which wheels were locked for 5, 53, or 173 hours (WL5, WL53, WL173) prior to sacrifice. During the 53 and 173 hours of inactivity, one group of animals was pair fed (PF) to match sedentary controls while the other continued to eat ad libitum (AL). Epididymal and retroperitoneal fat masses were significantly increased in the WL173PF versus WL5 group, while epididymal, perirenal, and retroperitoneal fat masses where all significantly increased in the WL173AL group compared WL5 group.

ABSTRACT Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stabl... more ABSTRACT Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli beta-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

The Faseb Journal, Apr 1, 2007

Arch Biochem Biophys, 1975

Thyrotoxicosis can induce increases in the concentrations of the cytochromes of the inner mitocho... more Thyrotoxicosis can induce increases in the concentrations of the cytochromes of the inner mitochondrial membrane in rat liver. The purpose of this study was to.

Journal of Applied Physiology, 2010

ABSTRACT None required for viewpoint Key words: None required.

Biochemistry Usa, 2003

Serum response factor (SRF) is a phosphoprotein that regulates skeletal and cardiac R-actin gene ... more Serum response factor (SRF) is a phosphoprotein that regulates skeletal and cardiac R-actin gene transcription. Myotonic dystrophy protein kinase (DMPK), a muscle-and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac R-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. DMPK phosphorylated SRF in vitro in the RI coil of the DNA-binding domain in the MADS box, a highly conserved region required for DNA binding, dimerization, and coactivator interaction in COS and CV1 cells. Threonine 159 in the MADS box RI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-R. Substitution of threonine 159 with the nonphosphorylatable residue alanine markedly diminished activation of the cardiac R-actin promoter in the presence of kinase, while its substitution with aspartic acid, to introduce a negative charge and mimic phosphorylation, restored activation completely. Phosphorylation of the MADS box may constitute a novel mechanism for regulation of SRF-dependent actin gene transcription.

Med Sci Sport Exercise, 1997

Jas, 2007

Pattison, J. Scott, Lillian C. Folk, Richard W. Madsen, and Frank W. Booth. Selected Contribution... more Pattison, J. Scott, Lillian C. Folk, Richard W. Madsen, and Frank W. Booth. Selected Contribution: Identification of differentially expressed genes between young and old rat soleus muscle during recovery from immobilizationinduced atrophy. After cessation of hindlimb immobilization, which resulted in a 27-37% loss in soleus mass, the atrophied soleus muscle of young but not old rats regrows to its mass before treatment. We hypothesized that during remobilization the mRNA levels of growth potentiating factor(s) would be present in the soleus muscle of young (3-to 4-mo-old) but absent in old (30to 31-mo-old) Fischer 344 ϫ Brown Norway rats or that mRNAs for growth inhibitory factor(s) would be absent in young but present in old. Gene expression levels of Ͼ24,000 transcripts were determined by using Affymetrix RGU34A-C high-density oligonucleotide microarrays in soleus muscles at 3, 6, 10, and 30 days of remobilization after cessation of a 10-day period of hindlimb immobilization. Each muscle sample was applied to an independent set of arrays. Recoveryrelated differences were determined by using a three-factor ANOVA with a false discovery rate-adjustment of P ϭ 0.01, which yielded 64 significantly different probe sets. Elfin, amphiregulin, and clusterin mRNAs were selected for further confirmation by real-time PCR. Elfin mRNA levels were less in old than in young rats at 6, 10, and 30 days of remobilization. Amphiregulin expression exhibited a unique spike on the 10th day of successful regrowth in young rats but remained unchanged old. Clusterin mRNA was unchanged in young muscles but was elevated on the 3rd, 6th, and 10th days of recovery in old soleus muscles. The mRNAs identified as differentially expressed between young and old recovery may modulate muscle growth that could highlight new candidate mechanisms to explain the failure of old soleus muscle to recover lost muscle mass. aged; mRNA; rehabilitation; growth THE INHERENT VALUE THAT SKELETAL muscle mass and strength play in overall health and homeostasis has been somewhat underappreciated. For example, the

Med Sci Sport Exercise, 1996

American Journal of Physiology Regulatory Integrative and Comparative Physiology, Aug 1, 1999

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle ma... more Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation (r = 0.725, P &amp;lt; 0. 0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

Journal of Applied Physiology, 2004

Various cellular signaling pathways, such as phosphatidylinositol 3-kinase, calcineurin, Janus ki... more Various cellular signaling pathways, such as phosphatidylinositol 3-kinase, calcineurin, Janus kinase 2/signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) have been suggested to play an important role in skeletal muscle growth. Old muscle, compared with young muscle, lacks the ability to completely regrow its muscle mass after an atrophy-induced stimulus. it is hypothesized that defects and/or delays in the activation of specific cell signaling pathways of aged soleus muscle limit the potential for growth. To test this, 42 male Fischer 344 x Brown Norway rats, 30 mo old, were hindlimb immobilized for 10 days, and their muscle samples were compared with muscle samples analyzed from 3- to 4-mo-old rats in a previous report (Childs TE, Spangenburg EE, Vyas DR, and Booth FW. Am J Physiol Cell Physiol: 285: C391-C398, 2003). After 10 days, the immobilization was removed and rats were allowed to ambulate for a series of days. Alterations in the activation or deactivation status of specific signaling pathways were determined by comparing the phosphorylation (phos) and total concentration of specific signaling proteins (pan) through Western blotting with the 10-day immobilization group. Various cell signals and their respective time groups of the old rats were shown to be significantly different compared with the 10-day immobilization group. For example, peak increases during recovery from the immobilization were observed at 1) the third recovery day for calcineurin B-pan and 2) the sixth recovery day for glycogen synthase kinase-3beta-phos, p70 S6 kinase (p70S6k) -phos and -pan, calcineurin A-pan, STAT3-phos and -pan, p44 MAPK-pan, and p42 MAPK-pan. In contrast, Akt-pan, c-Jun NH2-terminal kinase-phos, and p38 MAPK-phos were observed to decrease from 10-day immobilization values to control levels. Also, Aktphos was unchanged among all groups. In a follow-up experiment in which muscle samples from both the present study and a previous study (Childs TE, Spangenburg EE, Vyas DR, and Booth FW. Am J Physiol Cell Physiol: 285: C391-C398, 2003) were reanalyzed together, the recovery-induced increase in p70S6k-phos from immobilization-atrophy was significantly attenuated in soleus muscles of the old group.

International Journal of Sports Medicine, Nov 1, 1997

Skeletal muscle adapts to loading; atrophying when exposed to unloading on Earth or in spacefligh... more Skeletal muscle adapts to loading; atrophying when exposed to unloading on Earth or in spaceflight. Significant atrophy (decreases in muscle fiber cross-section of 11-24%) in humans has been noted after only 5 days in space. Since muscle strength is determined both by muscle cross-section and synchronization of motor unit recruitment, a loss in muscle size weakens astronauts, which would increase risks to their safety if an emergency required maximal muscle force. Numerous countermeasures have been tested to prevent atrophy. Resistant exercise together with growth hormone and IGF-I are effective countermeasures to unloading as most atrophy is prevented in animal models. The loss of muscle protein is due to an early decrease in protein synthesis rate and a later increase in protein degradation. The initial decrease in protein synthesis is a result of decreased protein translation, caused by a prolongation in the elongation rate. A decrease in HSP70 by a sight increase in ATP may be the factors prolonging elongation rate. Increases in the activities of proteolytic enzymes and in ubiquitin contribute to the increased protein degradation rate in unloaded muscle. Numerous mRNA concentrations have been shown to be altered in unloaded muscles. Decreases in mRNAs for contractile proteins usually occur after the initial fall in protein synthesis rates. Much additional research is needed to determine the mechanism by which muscle senses the absence of gravity with an adaptive atrophy. The development of effective countermeasures to unloading atrophy will require more research.

Journal of Applied Physiology, 2000

Spikes in free Ca(2+) initiate contractions in skeletal muscle cells, but whether and how they mi... more Spikes in free Ca(2+) initiate contractions in skeletal muscle cells, but whether and how they might signal to transcription factors in skeletal muscles of living animals is unknown. Since previous studies in non-muscle cells have shown that serum response factor (SRF) protein, a transcription factor, is phosphorylated rapidly by Ca(2+)/calmodulin (CaM)-dependent protein kinase after rises in intracellular Ca(2+), we measured enzymatic activity that phosphorylates SRF (designated SRF kinase activity). Homogenates from 7-day-hypertrophied anterior latissimus dorsi muscles of roosters had more Ca(2+)-independent SRF kinase activity than their respective control muscles. However, no differences were noted in Ca(2+)/CaM-dependent SRF kinase activity between control and trained muscles. To determine whether the Ca(2+)-independent and Ca(2+)/CaM-dependent forms of Ca(2+)/CaM-dependent protein kinase II (CaMKII) might contribute to some of the SRF kinase activity, autocamtide-3, a synthetic substrate that is specific for CaMKII, was employed. While the Ca(2+)-independent form of CaMKII was increased, like the Ca(2+)-independent form of SRF kinase, no alteration in CaMKII occurred at 7 days of stretch overload. These observations suggest that some of SRF phosphorylation by skeletal muscle extracts could be due to CaMKII. To determine whether this adaptation was specific to the exercise type (i.e., hypertrophy), similar measurements were made in the white vastus lateralis muscle of rats that had completed 2 wk of voluntary running. Although Ca(2+)-independent SRF kinase was increased, no alteration occurred in Ca(2+)/CaM-dependent SRF kinase activity. Thus any role of Ca(2+)-independent SRF kinase signaling has downstream modulators specific to the exercise phenotype.

Journal of the Neurological Sciences, Jun 1, 2003

This study assessed the effect of muscle unloading on the neuromuscular system. Sixteen male Fisc... more This study assessed the effect of muscle unloading on the neuromuscular system. Sixteen male Fischer 344 rats were randomly assigned to either a hindlimb suspension (unloaded) or control group (N = 8/group) for 16 days. Following this intervention period, pre-and postsynaptic features of the neuromuscular junctions (NMJs) of soleus muscles were stained with cytofluorescent techniques, and myofibers were histochemically stained for ATPase activity. The data indicate that 16 days of muscle unloading resulted in significant ( P < 0.05) atrophy among myofibers (>50%) that was evident among all three major fiber types (I, IIA and IIX), but failed to significantly alter any aspect of NMJ morphology quantified. These results demonstrate an impressive degree of NMJ resilience despite dramatic remodeling of associated myofibers. This may be of benefit during post-unloading rehabilitative measures where effective neuromuscular communication is essential. D

Medicine and Science in Sports and Exercise, 2004

The current state of knowledge regarding regrowth of skeletal muscle after inactivity-induced atr... more The current state of knowledge regarding regrowth of skeletal muscle after inactivity-induced atrophy is reviewed. Muscle regrowth is incomplete after hindlimb suspension in juvenile rats and after limb immobilization in old animals. The process of regrowth from immobilization-induced atrophy likely involves the reversal of directional changes in molecules producing muscle loss while initiating anabolic processes for regrowth of muscle mass. Unfortunately, the molecular mechanisms responsible for successful, or failed, muscle regrowth are not well understood. The purpose of the review is to provide current knowledge about the biology of muscle regrowth from inactivity-induced atrophy.

Eur J Appl Physiol, 1969

ABSTRACT

Physiol Genomics, 2006

Booth FW, Lees SJ. Fundamental questions about genes, inactivity, and chronic diseases.