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F W Booth

Publications and source records attributed to F W Booth.

At least 37 records · Page 2Linked to original sources

Waging war on modern chronic diseases: primary prevention through exercise biology.

In this review, we develop a blueprint for exercise biology research in the new millennium. The first part of our plan provides statistics to support the contention that there has been an epidemic emergence of modern chronic diseases in the latter part of the 20th century. The health care costs of these conditions were almost two-thirds of a trillion dollars and affected 90 million Americans in 1990. We estimate that these costs are now approaching $1 trillion and stand to further dramatically increase as the baby boom generation ages. We discuss the reaction of the biomedical establishment to this epidemic, which has primarily been to apply modern technologies to stabilize overt clinical problems (e.g., secondary and tertiary prevention). Because this approach has been largely unsuccessful in reversing the epidemic, we argue that more emphasis must be placed on novel approaches such as primary prevention, which requires attacking the environmental roots of these conditions. In this respect, a strong association exists between the increase in physical inactivity and the emergence of modern chronic diseases in 20th century industrialized societies. Approximately 250,000 deaths per year in the United States are premature due to physical inactivity. Epidemiological data have established that physical inactivity increases the incidence of at least 17 unhealthy conditions, almost all of which are chronic diseases or considered risk factors for chronic diseases. Therefore, as part of this review, we present the concept that the human genome evolved within an environment of high physical activity. Accordingly, we propose that exercise biologists do not study "the effect of physical activity" but in reality study the effect of reintroducing exercise into an unhealthy sedentary population that is genetically programmed to expect physical activity. On the basis of healthy gene function, exercise research should thus be viewed from a nontraditional perspective in that the "control" group should actually be taken from a physically active population and not from a sedentary population with its predisposition to modern chronic diseases. We provide exciting examples of exercise biology research that is elucidating the underlying mechanisms by which physical inactivity may predispose individuals to chronic disease conditions, such as mechanisms contributing to insulin resistance and decreased skeletal muscle lipoprotein lipase activity. Some findings have been surprising and remarkable in that novel signaling mechanisms have been discovered that vary with the type and level of physical activity/inactivity at multiple levels of gene expression. Because this area of research is underfunded despite its high impact, the final part of our blueprint for the next millennium calls for the National Institutes of Health (NIH) to establish a major initiative devoted to the study of the biology of the primary prevention of modern chronic diseases. We justify this in several ways, including the following estimate: if the percentage of all US morbidity and mortality statistics attributed to the combination of physical inactivity and inappropriate diet were applied as a percentage of the NIH's total operating budget, the resulting funds would equal the budgets of two full institutes at the NIH! Furthermore, the fiscal support of studies elucidating the scientific foundation(s) targeted by primary prevention strategies in other public health efforts has resulted in an increased efficacy of the overall prevention effort. We estimate that physical inactivity impacts 80-90% of the 24 integrated review group (IRG) topics proposed by the NIH's Panel on Scientific Boundaries for Review, which is currently directing a major restructuring of the NIH's scientific funding system. Unfortunately, the primary prevention of chronic disease and the investigation of physical activity/inactivity and/or exercise are not mentioned in the almost 200 total subtopics comprising t

Cardiovascular Diseases↗

IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle.

One of the key factors responsible for the age-associated reduction in muscle mass may be that satellite cell proliferation potential (number of doublings contained within each cell) could become rate limiting to old muscle regrowth. No studies have tested whether repeated cycles of atrophy-regrowth in aged animals deplete the remaining capacity of satellite cells to replicate or what measures can be taken to prevent this from happening. We hypothesized that there would be a pronounced loss of satellite cell proliferative potential in gastrocnemius muscles of aged rats (25- to 30-mo-old FBN rats) subjected to three cycles of atrophy by hindlimb immobilization (plaster casts) with intervening recovery periods. Our results indicated that there was a significant loss in gastrocnemius muscle mass and in the proliferative potential of the resident satellite cells after just one bout of immobilization. Neither the muscle mass nor the satellite cell proliferation potential recovered from their atrophied values after either the first 3-wk or later 9-wk recovery period. Remarkably, application of insulin-like growth factor I onto the atrophied gastrocnemius muscle for an additional 2 wk after this 9-wk recovery period rescued approximately 46% of the lost muscle mass and dramatically increased proliferation potential of the satellite cells from this muscle.

Aging↗

Pulmonary hypoplasia in the myogenin null mouse embryo.

Although fetal breathing movements are required for normal lung development, there is uncertainty concerning the specific effect of absent fetal breathing movements on pulmonary cell maturation. We set out to evaluate pulmonary development in a genetically defined mouse model, the myogenin null mouse, in which there is a lack of normal skeletal muscle fibers and thus skeletal muscle movements are absent in utero. Significant decreases were observed in lung:body weight ratio and lung total DNA at embryonic days (E)14, E17, and E20. Reverse transcriptase/polymerase chain reaction, in situ immunofluorescence, and electron microscopy revealed early lung cell differentiation in both null and wild-type lungs as early as E14. However at E14, myogenin null lungs had decreased 5'-bromo-2-deoxyuridine incorporation compared with that of wild-type littermates, whereas at E17 and E20, increased Bax immunolabeling and terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining were detected in the myogenin null mice but not in the wild-type littermates. These observations highlight the importance of skeletal muscle contractile activity in utero for normal lung organogenesis. Null mice lacking the muscle-specific transcription factor myogenin exhibit a secondary effect on lung development such that decreased lung cell proliferation and increased programmed cell death are associated with lung hypoplasia.

Animals↗

Human bHLH transcription factor gene myogenin (MYOG): genomic sequence and negative mutation analysis in patients with severe congenital myopathies.

The myogenin gene encodes an evolutionarily conserved basic helix-loop-helix transcription (bHLH) factor that is required for differentiation of skeletal muscle, and its homozygous deletion in mice results in perinatal death from respiratory failure due to the lack of muscle fibers. Since the histology of skeletal muscle in myogenin null mice is reminiscent of that found in severe congenital myopathy patients, many of whom also die of respiratory complications, we sought to test the hypothesis that an aberrant human myogenin (myf4) coding region could be associated with some congenital myopathy conditions. With PCR amplification, we found similarly sized PCR products for the three exons of the myogenin gene in DNA from 37 patient and 40 control individuals. In contrast to previously reported sequencing of human myogenin (myf4), we describe with automated sequencing several base differences in flanking and coding regions plus an additional 659 and 498 bp in the first and second introns, respectively, in all 37 patient and 40 control samples. We also find a variable length (CA)-dinucleotide repeat in the second intron, which may have utility as a marker for future linkage studies. In summary, no causative mutations were detected in the myogenin coding locus of genomic DNA from 37 patients with severe congenital myopathy.

Base Sequence↗

Focal adhesion proteins FAK and paxillin increase in hypertrophied skeletal muscle.

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.

Animals↗

Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading.

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 < 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.

Animals↗

Serum response factor mRNA induction in the hypertrophying chicken patagialis muscle.

Gene expression in the stretched chicken patagialis (Pat) muscle has not been extensively examined. This study's purpose was to determine the Pat muscle's expression pattern of serum response factor (SRF), skeletal alpha-actin, and MyoD mRNAs after 3 days (onset of stretch), 6 days (end of first week of rapid growth), and 14 days (slowed rate of stretch-induced growth) of stretch. SRF mRNA demonstrated two species (B1 and B2), with B2 being more prevalent in the predominantly fast-twitch Pat muscle, compared with the slow-tonic muscle. Stretch overload increased B1 and B2 SRF mRNA concentrations, and the increase in B1 SRF mRNA concentration was greater at day 6 compared with days 3 or 14. MyoD mRNA concentration was greater in 3-day-stretched Pat muscles, compared with days 6 or 14. Skeletal alpha-actin mRNA concentration was not changed during the study. Gel mobility shift assays demonstrated that SRF binding with serum response element 1 of the skeletal alpha-actin promoter had no altered binding patterns from 6-day-stretched Pat nuclear extracts. It appears that SRF and MyoD mRNAs are induced in the stretch-overloaded Pat muscle but at different time points.

Actins↗

SRF protein is upregulated during stretch-induced hypertrophy of rooster ALD muscle.

Serum response element 1 has previously been reported to be necessary and sufficient for activation of the skeletal alpha-actin promoter during hypertrophy of the anterior latissimus dorsi (ALD) muscle of roosters [J. A. Carson, R. J. Schwartz, and F. W. Booth. Am. J. Physiol. 270 (Cell Physiol. 39): C1624-C1633, 1996]. Serum response factor (SRF) protein is the transcription factor that binds as a homodimer to serum response element 1 and activates the skeletal alpha-actin promoter. An increased expression of exogenous SRF protein in replicating C2C12 myoblasts induced a three- to fourfold activation of the skeletal alpha-actin promoter (L. Wei, W. Zhou, J. D. Croissant, F.-E. Johansen, R. Prywes, A. Balasubramamyan, and R. J. Schwartz. J. Biol. Chem. 273: 30287-30294, 1998). Thus we hypothesized that SRF protein concentration would be increased during hypertrophy of skeletal muscle. In the present study, 10% of the rooster's body weight was attached to the left wing to induce enlargement of the ALD muscle compared with the contralateral muscle. With Western analysis, a significant increase in SRF protein per gram of wet weight of the ALD muscle was noted at 7 and 13 days of hypertrophy. Furthermore, the increase in SRF protein occurred in both crude nuclear protein and cytoplasmic fractions in 7-day stretched ALD muscles. This is the first report showing increased protein concentration for a transcription factor whose regulatory element in the skeletal alpha-actin promoter has previously been shown to be required for the transduction of a hypertrophy signal in overloaded skeletal muscle of an animal.

Animals↗

The force-frequency relationship is altered in regenerating and senescent rat skeletal muscle.

Maximal tetanic tension was elicited at 200, 150, and 150 Hz in control tibialis anterior muscles and at 150, 100, and 100 Hz in 14-day regenerating muscles of young (3 months), adult (18 months), and old (31 months) Fischer 344/Brown Norway F1 rats, respectively. In contrast to young rats, increasing stimulation frequency from 50 to 150 Hz did not elicit significantly greater tetanic tension in control or regenerating muscles of old rats. At higher stimulation frequencies, tetanic fade was prevalent in control and regenerating muscles of adult (250-300 Hz) and old rats (200-300 Hz), but was only present at 14 days of recovery in regenerating muscles of young rats (300 Hz). The decreased efficacy of rehabilitative and physical medicine procedures in adult and elderly patients who have suffered skeletal muscle injury could be explained, in part, by the postulate that tetanic fade is indicative of inadequate synaptic transmission.

Aging↗

Myogenin mRNA is elevated during rapid, slow, and maintenance phases of stretch-induced hypertrophy in chicken slow-tonic muscle.

Biochemical changes that are associated with the growth phase of stretch-induced skeletal muscle hypertrophy are better understood than events that maintain the increased muscle mass. One purpose of this study was to determine whether changes that occur during the period of rapid muscle hypertrophy persist during periods when muscle growth plateaus or the rate of enlargement slows. Serum response factor (SRF), myogenin, MyoD, and actin mRNA expression patterns were examined. SRF protein interactions with serum response element-1 (SRE1) of the chicken skeletal alpha-actin gene were also characterized. Anterior latissimus dorsi (ALD) wet weight (132% and 122%) and total RNA concentration (29% and 19%) increased after 2 and 3 weeks of stretch overload, respectively. Myogenin mRNA per microgram RNA increased after 3 (775%), 6 (1073%), 14 (227%), and 21 days (133%) of stretch overload. At 6 days, myogenin mRNA levels were increased in the distal, middle and proximal regions of the ALD. Serum response factor (SRF) mRNA per microgram total RNA was not increased after 2 or 3 weeks of stretch overload. MyoD and skeletal alpha-actin mRNAs per microgram total RNA were also unchanged after 2 and 3 weeks of stretch. Gel mobility shift assays demonstrated that SRF bound to SRE1 from 14-day-stretched ALD nuclear extracts had an increased mobility compared to control, and this difference in mobility was maintained in nuclear extracts from ALD muscle whose mass was declining. These results indicate that the expression of myogenin mRNA and total RNA remains elevated during either slow or maintenance periods of stretch-induced increases in ALD mass, when SRF mRNA has returned to control levels. Additionally, stretch-induced alterations in SRF binding to SRE1, from the skeletal alpha-actin promoter, occur regardless of the rate of stretch-induced growth.

Actins↗

Activation of the skeletal alpha-actin promoter during muscle regeneration.

Little is known concerning promoter regulation of genes in regenerating skeletal muscles. In young rats, recovery of muscle mass and protein content is complete within 21 days. During the initial 5-10 days of regeneration, mRNA abundance for IGF-I, myogenin and MyoD have been shown to be dramatically increased. The skeletal alpha-actin promoter contains E box and serum response element (SRE) regulatory regions which are directly or indirectly activated by myogenin (or MyoD) and IGF-I proteins, respectively. We hypothesized that the skeletal alpha-actin promoter activity would increase during muscle regeneration, and that this induction would occur before muscle protein content returned to normal. Total protein content and the percentage content of skeletal alpha-actin protein was diminished at 4 and 8 days and re-accumulation had largely occurred by 16 days post-bupivacaine injection. Skeletal alpha-actin mRNA per whole muscle was decreased at day 8, and thereafter returned to control values. During regeneration at day 8, luciferase activity (a reporter of promoter activity) directed by -424 skeletal alpha-actin and -99 skeletal alpha-actin promoter constructs was increased by 700% and 250% respectively; however, at day 16, skeletal alpha-actin promoter activities were similar to control values. Thus, initial activation of the skeletal alpha-actin promoter is associated with regeneration of skeletal muscle, despite not being sustained during the later stages of regrowth. The proximal SRE of the skeletal alpha-actin promoter was not sufficient to confer a regeneration-induced promoter activation, despite increased serum response factor protein binding to this regulatory element in electrophoretic mobility shift assays. Skeletal alpha-actin promoter induction during regeneration is due to a combination of regulatory elements, at least including the SRE and E box.

Actins↗

Molecular and cellular adaptation of muscle in response to physical training.

Molecular biology tools can be used to answer questions as to how adaptations occur in skeletal muscle with training that could provide new frameworks to improve physical performance. A number of mRNAs for transfer of metabolic substrates into muscle cells increase after a single bout of exercise demonstrating the responsiveness of some gene expression to exercise. In stretch-induced hypertrophy SRE1 of the skeletal alpha-actin promoter is required to transactivate the promoter. Less retardation of SRF in crude nuclear extracts from the stretched muscle implies a conformational change in SRF because of the stretch. Transgenic animals will provide a tool to test questions concerned with how exercise signals adaptive changes in gene expression. Molecular biological approaches will be able to evaluate the interaction between physical activity levels and the expression of genes that modulate the susceptibility to many chronic diseases. Benefits of exercise extend beyond fitness to better health. Molecular biology is an important tool which should lead to improved physical performance and health in both elite athletes and the general public.

Adaptation, Physiological↗

Effect of serum and mechanical stretch on skeletal alpha-actin gene regulation in cultured primary muscle cells.

The purpose of this study was to determine whether mechanical stretch or serum availability alters pretranslational regulation of skeletal alpha-actin (SkA) in cultured striated muscle cells. Chicken primary skeletal myoblasts and cardiac myocytes were plated on collagenized Silastic membranes adherent to nylon supports and stretched 8-20% of initial length 96 h postplating. Serum dependence of SkA gene regulation was determined by maintaining differentiated muscle cells in growth/differentiation (G/D; skeletal myotubes, 10% horse serum-2% chick embryo extract; cardiac myocytes, 10% horse serum) or growth-limiting (G-L; 0.5% horse serum) medium. Skeletal myotubes had higher SkA mRNA and SkA promoter activity in G/D than in G-L medium. Cardiac myocyte SkA mRNA was higher in G-L than in G/D medium. Serum response factor (SRF) protein binding to serum response element 1 (SRE1) of SkA promoter increased in skeletal cultures in G/D compared with G-L medium. Western blot analysis demonstrated that increased SRF-SRE1 binding was due, in part, to increased SRF protein. Stretching skeletal myotubes in G-L medium reduced SkA mRNA and repressed SkA promoter activity. The first 100 bp of SkA promoter were sufficient for stretch-induced repression of SkA promoter activity, and an intact transcriptional enhancer factor 1 (TEF-1) binding site was necessary for this response. Serum and stretch appear to repress SkA promoter activity in skeletal myotubes through different DNA binding elements, the SRE1 and TEF-1 sites, respectively. Stretching increased SkA mRNA in cardiac myocytes in G-L medium but did not alter SkA mRNA level in cardiac cells in G/D medium. These results demonstrate that stretch and serum interact differently to alter SkA expression in cultured cardiac and skeletal muscle cells.

Actins↗

Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy.

This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P < 0.05) after HU in both IGF-I (-9%) and FVB mice (-13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced (P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.

Actins↗

Nerve-responsive troponin I slow promoter does not respond to unloading.

We examined the regulation of the troponin I slow (TnIs) promoter during skeletal muscle unloading-induced protein isoform transition, by using a transgenic mouse line harboring the -4,200 to +12 base pairs region of the human TnIs promoter. Eighteen female transgenic mice ( approximately 30 g body mass) were randomly divided into two groups: weight-bearing (WB) controls (n = 9) and hindlimb unloaded (HU; n = 9). The HU mice were tail suspended for 7 days. Body mass was unchanged in the WB group but was reduced (-6%; P < 0.05) after the HU treatment. Absolute soleus muscle mass (-25%) and soleus mass relative to body mass (-16%) were both lower (P < 0.05) in the HU group compared with the WB mice. Northern blot analyses indicate that 7 days of HU result in a 64% decrease (P < 0.05) in the abundance of endogenous TnIs mRNA (microg/mg muscle) in the mouse soleus. Furthermore, there is a trend for the abundance of the fast troponin I mRNA to be increased (+34%). Analysis of transgenic chloramphenicol acetyltransferase activity in the soleus muscle revealed no difference (P > 0.05) between WB and HU groups. We conclude that additional elements are necessary for the TnIs gene to respond to an unloading-induced, slow-to-fast isoform transition stimulus.

Animals↗

Cytochrome c promoter activity in soleus and white vastus lateralis muscles in rats.

Cytochrome c protein and mRNA are 300 and 100% higher, respectively, in the soleus muscle (predominantly slow-twitch oxidative) than the white vastus lateralis (predominately fast-twitch glycolytic) muscle (W. W. Winder, K. M. Baldwin, and J. O. Holloszy. Eur. J. Biochem. 47: 461-467, 1974; M. M. Lai and F. W. Booth. J. Appl. Physiol. 69: 843-848, 1990). However, the mechanisms controlling these differences in cytochrome c mRNA are largely unknown. The present study employed direct plasmid injection techniques to determine whether the proximal promoter (-726 to +610) of the rat somatic cytochrome c gene was more active in the soleus than in white vastus lateralis muscles in rats. No difference between the soleus and white vastus lateralis muscles for the activities of the -726, -631, -489, -326, -215, -159 and -149 cytochrome c promoters was noted. The results of this study suggest that additional elements (outside of -726 to +610) in the cytochrome c gene may be required, or posttranscriptional regulation may account, for the higher cytochrome c mRNA in the slow-twitch oxidative muscle.

Animals↗

Expression of acetylcholine receptor mRNAs in atrophying and nonatrophying skeletal muscles of old rats.

We examined the age-related association in skeletal muscle between atrophy and expression of mRNAs encoding both the gamma-subunit of the nicotinic acetylcholine receptor (AChR), and myogenin, a transcription factor that upregulates expression of the gamma-subunit promoter. Gastrocnemius and biceps brachii muscles were collected from young (2-mo-old), adult (18-mo-old), and old (31-mo-old) Fischer 344/Brown Norway F1 generation cross male rats. In the gastrocnemius muscles of old vs. young and adult rats, lower muscle mass was accompanied by significantly elevated AChR gamma-subunit and myogenin mRNA levels. In contrast, the biceps brachii muscle exhibited neither atrophy nor as drastic a change in AChR gamma-subunit and myogenin mRNA levels with age. Expression of the AChR epsilon-subunit mRNA did not change with age in either gastrocnemius or biceps brachii muscles. Thus changes in skeletal muscle AChR gamma-subunit and myogenin mRNA levels may be more related to atrophy than to chronological age in old rats.

Animals↗

Chronic stimulation differentially modulates expression of mRNA for dihydropyridine receptor isoforms in rat fast twitch skeletal muscle.

This study examined the effects of low frequency chronic stimulation on expression of the mRNA encoding the two isoforms of the alpha1 subunit of the dihydropyridine receptor (DHPR) calcium channel, a critical component of skeletal muscle excitation-contraction coupling. RNase protection assay was used to determine alteration in isoform expression in 5-day, 9-day and 13-day chronically stimulated rat tibialis anterior muscle, and to compare it with soleus and extensor digitorum longus muscles. Low frequency chronic stimulation was associated not only with a significant decrease in the mRNA level of the skeletal isoform of the DHPR, but also with a significant increase in the mRNA level of the cardiac isoform of the DHPR, the overwhelming majority of which was the adult splice variant. Significant levels of cardiac DHPR mRNA expression were also found in normal adult slow twitch soleus muscle. These findings raise the question of a potential role for the cardiac DHPR in certain adult skeletal muscles.

Alternative Splicing↗