| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
MUSCLE CELL BIOLOGY AND CELL MOTILITY
1Departments of Orthopaedics, Bioengineering, and Medicine and Biomedical Sciences Graduate Group, University of California and Department of Veterans Affairs Medical Center, San Diego, California; and 2Muscle Biology Laboratory, University of Wisconsin-Madison, Madison, Wisconsin
Submitted 8 February 2007 ; accepted in final form 19 March 2007
 |
ABSTRACT |
|---|
 TOP ABSTRACT METHODSRESULTSDISCUSSIONGRANTSREFERENCES |
|---|
CARP; Ankrd2; Arpp; DARP; eccentric contractions; titin
Recent gene array studies provided clues into the types of genes that are upregulated after ECs and therefore may be important in muscle's response to this type of exercise. A recent study (4) revealed that 36 genes were upregulated 48 h after a single bout of EC. Of these 36 genes, two were members of the three-member muscle ankyrin repeat protein (MARP) family: cardiac ankyrin repeat protein (CARP) and ankyrin repeat protein with PEST and proline-rich region/ankyrin repeat domain 2 (Arpp/Ankrd2; Ankrd2). The third member of the family, diabetes-associated ankyrin repeat protein, or DARP (15), was not present on the original chip, but all MARP family members share 
50% homology and similar intracellular distributions (26). The MARP family is a unique group of proteins that are found in differing abundance in the central I band of the sarcomere in both cardiac and skeletal muscles, where they bind the N2A region of titin (26) and the amino terminus of the nebulin anchoring protein myopalladin (3). They are found in both the nucleus and the cytoplasm of skeletal and cardiac tissue (17, 42, 48), and at least one family member, CARP, has been suggested to act as a transcription inhibitor that acts downstream of the homeobox gene Nkx2.5 (19, 48) Ankrd2 has also been shown to bind to YB-1, PML, and p53, suggesting a role in signaling (23).
CARP is also known as C-193 and was originally discovered as a cytokine-inducible gene in fibroblasts (11) before it was recognized as differentially regulated between embryonic and adult heart (7, 19, 24, 48). As its name suggests, in adult animals CARP is primarily expressed in cardiac tissue, where it is thought to be a marker for cardiac hypertrophy (1, 24). In skeletal muscle, CARP is upregulated in muscle from patients suffering from Duchenne muscular dystrophy (2) as well as other dystrophies (29, 30) and in response to acute resistance exercise (10) or work-overload hypertrophy (9). Ankrd2 is similar to CARP, although it is more highly expressed in skeletal than cardiac muscle, preferentially in type 1 fibers (21, 42). Its expression in skeletal muscle is increased with denervation (42), with immobilization in a stretched position, with differentiation in culture (21), and in tumors (18). DARP is expressed in both heart and skeletal muscle (in addition to brown fat) and was identified by its upregulation in Type 2 diabetes and insulin-resistant animals, suggesting a potential role in energy metabolism (15).
Despite the evidence suggesting that the MARP family is important for the structure and function of striated muscle, the precise role that it plays in muscle remains unclear. The consistent and robust increase in expression of these genes after various physiological stimuli, including EC-induced muscle injury, suggests that these genes may play an important role in the response of muscle to these stimuli, and perhaps in the normal structure of muscle. Thus the three members of the MARP family are excellent candidates for proteins that both serve a structural role and act as mechanically sensitive signal transducers within striated muscle.
Our hypothesis is that the MARP family members may be key players in either the structural stability of skeletal muscle, particularly in regard to either muscle morphology and phenotype or its ability to withstand ECs, or the gene expression response and remodeling after injury. We present the results of a detailed analysis of the skeletal muscle phenotype of mice lacking each MARP family member individually, double knockouts lacking either CARP and DARP or Ankrd2 and DARP, and triple MARP knockout (MKO) mice, lacking all three members of the MARP family. Our results suggest that while the MARP family is not essential for the basal functioning of skeletal muscle, with only mild effects on fiber size or fiber type distribution, it plays a role in the passive mechanical behavior and the structural stability of the tissue after ECs. In addition, gene expression results suggest that the MARP family may serve a modulatory role in the regenerative response in muscle, such that MKO mice showed an enhanced regenerative response to EC-induced muscle injury. Our results also suggest that these three proteins are not only structurally but also functionally homologous, with the necessity for all three genes being removed to see a significant effect on the performance of the muscle.
|
METHODS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
|---|
|
SDS-PAGE.
Fiber type analysis was performed on the TA, EDL, and soleus of wild-type and KO animals with a modified version of the SDS-PAGE method developed by Talmadge and Roy (41). Either a 55-µm-thick section of the muscle (for muscle fiber type percentage analysis) or a single-fiber segment (for determination of fiber type after passive mechanics) was dissolved in sample buffer [100 mM dithiothreitol, 2% SDS, 80 mM Tris base pH 6.8, 10% glycerol, and 1.2% (wt/vol) bromophenol blue], boiled for 2 min, and then either frozen at –80°C or run immediately on the gel. Stacking and resolving gels, with a total gel size of 16 cm x 22 cm, were 4% and 8% acrylamide, respectively, and 0.75 mm thick. They were run at a constant voltage of 275 V for 21 h at 4°C and then silver stained according to the manufacturer's protocol (Bio-Rad, Hercules, CA). Fiber type percentage analysis was performed in duplicate or triplicate and analyzed with NIH Image (version 1.62). Single-fiber analysis was performed once, simply to determine the fiber type of the mechanically tested fiber.
Single-Fiber Mechanics. Passive mechanical experiments were performed on cells from either the fifth toe muscle of the EDL or the soleus muscle. These two muscles were chosen based on the fiber type and length homogeneity observed within each muscle (8) and the dramatically different fiber type profiles between muscles. Immediately after the animals were euthanized by cervical dislocation under general anesthesia, hindlimbs were transected proximal to the knee and placed into a mammalian Ringer solution (mM: 137 NaCl, 5 KCl, 24 NaH2PO4, 2 CaCl2, 1 MgSO4, and 11 glucose, with 10 mg/l curare). Occasionally, the contralateral limb from an exercised animal was used for mechanical experiments; in this case, hindlimbs were transected after the TA muscles were removed and frozen for RNA analysis (described below).
EDL and soleus muscles were quickly removed from the hindlimb and placed in a relaxing solution containing (mM) 59.4 imidazole, 86 KCH4O3S, 0.13 Ca(KCH4O3S)2, 10.8 Mg(KCH4O3S)2, 5.5 K3EGTA, 1 KH2PO4, and 5.1 Na2ATP, with 50 µM leupeptin (40), for at least 60 min. While in relaxing solution the fifth toe muscle of the EDL was dissected under magnification, and both this and the soleus were separated into two bundles for storage. These muscles were then pinned to Parafilm-coated cork and stored in a storage solution of (mM) 170 K propionate, 5 K3EGTA, 5.3 MgCl2, 10 imidazole, 21.2 Na2ATP, 1 NaN3, and 2.5 glutathione, with 50 µm leupeptin and 50% (vol/vol) glycerol (13), at –20°C for up to 3 wk.
At the time of the experiment, bundles were removed from storage solution and placed in relaxing solution. Single-fiber segments (2–3 mm in length) were carefully dissected and transferred to the mechanics chamber, where they were tied with 10-0 nylon suture to titanium wires (26601-9, Aldrich Chemical, Milwaukee, WI) secured to a force transducer (405A, Aurora Scientific) and a motor (318B, Aurora Scientific). The motor was connected to a micromanipulator such that fiber stretching could be controlled by either the motor or the micromanipulator and fiber orientation could be adjusted. Slack length was determined by a combination of visually orienting the fiber such that it did not have a curved appearance and maintaining the tension within 0.002 mV (<0.1 mg) of its background level. This method has been shown to be repeatable (14). Under x10 magnification, the fiber length and diameter in three places were measured by manipulating the fiber in and out of the field of view with a micrometer attached to a micromanipulator. Mean fiber diameter was used to estimate fiber cross-sectional area, assuming fibers were cylindrical. Fiber length was also determined by transilluminating the fiber with a He-Ne laser (Melles Griot, Irvine, CA) to permit measurement of the sarcomere length at slack length and after 0.5-mm stretch. Sarcomere length was determined by projecting the diffraction pattern onto a photodiode array (PDA; model S2048, Reticon) positioned above the fiber. The position of the PDA was calibrated by using 2.50-, 3.33-, and 5.0-µm diffraction gratings before the experiment, and first-order diffraction peaks were used to calculate sarcomere length according to standard grating equations. Fiber length was calculated, assuming constant sarcomere number, with the formula fiber length = 0.5 mm/(SLstretch/SLslack – 1), where SL is sarcomere length. The fiber length used in the final analysis was the average of both the visually determined and the calculated fiber length, which were within 0.5 mm of each other. The fiber was carefully checked for mechanical integrity such that any discoloration, abrasion, swelling, or disrupted diffraction pattern disqualified the fiber from further analysis. All experiments were performed at room temperature.
Dynamic experiments were performed using a Labview program (National Instruments, Austin, TX) to control the motor, record force from the force transducer, and record the diffraction pattern from the PDA. A preconditioning bout of stretches was performed by imposing five stretches at 20% strain and 20%/s strain rate. After 5-min rest, two stretch protocols consisting of five cycles of stretch and release at 35% strain were imposed on the muscle: low velocity (10%/s strain rate) and high velocity (100%/s strain rate). Sarcomere length and force were recorded in real time for both strain rates and analyzed with MATLAB (MathWorks, Natick, MA) for tangent modulus (final slope in the last 5% of each stretch cycle), hysteresis loop area, starting sarcomere length, peak sarcomere length, peak stress, and peak strain. After the dynamic stretch protocols, the muscle fibers were stretched to failure in 2-min intervals and 250-µm increments with the micrometer attached to the motor. Sarcomere length and tension were recorded at the end of each 2-min interval.
A separate set of EDL fibers were subjected to a progressive protocol of five cycles of stretch at 20%, 30%, 40%, 50%, and 60% strain and 5%/s strain rate in order to look for strain softening behavior and for tangent modulus differences at a slower strain rate. After this progression, stress relaxation was recorded by using the motor to stretch the fiber 20%, 30%, or 40% and hold at that length for 2 min. MATLAB was then used to calculate peak stress and steady-state stress and to fit an exponential equation to the stress relaxation decay in order to compare stress relaxation time constants among the genotypes. After mechanical testing, the fibers were placed in 10 µl of sample buffer and stored for fiber type analysis as described above.
Exercise protocol.
The exercise apparatus and regimen are described in detail elsewhere (4). In brief, mice were positioned in a specially designed jig that allowed measurement of ankle dorsiflexion torque and control of ankle position (to control muscle length) via an ergometer (custom-modified model 360B, Aurora Scientific) while under general anesthesia (2% isoflurane). The TA and EDL muscles were stimulated by sterile subcutaneous 28-gauge needle electrodes (Grass Instruments, Braintree, MA) placed in the vicinity of the right peroneal nerve, 0.5 mm under the skin, just lateral to the midline and distal to the knee joint. Stimulation voltage was usually 10 V, and optimum stimulation frequency (resulting in a flat and fused isometric torque record) was usually determined to be 200 Hz.
Before all exercise paradigms, maximal isometric torque was measured as the mean of two isometric contractions. The eccentric bout consisted of 50 ECs, 1/min, with the footplate forcing 78° of plantarflexion at 1 fiber length/s, starting 150 ms after the muscle was activated. During the EC bout, isometric twitches were recorded every five contractions and needle electrodes were repositioned if necessary to achieve a maximal twitch. The contralateral leg received only an isometric testing protocol, consisting of just enough isometric contractions (5) to determine and record maximum isometric torque, without ECs.
Mice were subjected to one of two protocols. The preliminary protocol followed four animals over time as they recovered from the injury protocol. Thus these animals were returned to their cage after the initial exercise bout and then subjected to the isometric testing protocol described above on both the eccentrically exercised and contralateral legs 6, 24, 72, 120, 168, and 216 h (9 days) after the initial bout. After the last testing time point, the animals were euthanized by cervical dislocation while under anesthesia. The second protocol collected muscles for analysis from the animals 6, 12, or 24 h after the initial exercise bout, with no intermediate testing. At the defined time point, TA muscles were removed and frozen in liquid nitrogen-cooled isopentane for further analysis, and the animals were euthanized by cervical dislocation while under anesthesia. The following seven genotypes were subjected to both protocols: wild type, CARPKO, Ankrd2KO, DARPKO, CARP/Ankrd2 double KO, CARP/DARP double KO, and MARP triple KO (MKO; Table 1).
RNA analysis. RNA was extracted from the TA muscles of exercised and contralateral legs with a combination of the standard TRIzol (Invitrogen, Carlsbad, CA) and RNeasy (Qiagen, Valencia, CA) protocols, described elsewhere (4). Five hundred nanograms of RNA from each sample was reverse transcribed with the manufacturer's protocol (Superscript II, Invitrogen). Quantitative real-time PCR was done with the Cepheid SmartCycler (Sunnyvale, CA), using primers specific to the genes of interest, and quantified by monitoring the fluorescence levels of the intercalating dye SYBR Green (Sigma) compared with a PCR product standard, as described elsewhere (4). Primers are listed in Table 2. All samples were run at least in duplicate, along with a standard. Amplification conditions were as follows: an initial hold at 95°C for 5 min was followed by 40 cycles of denaturing at 95°C for 15 s followed by annealing/extension at 66°C for 40 s (CARP and MyoD), 70°C for 40 s (Ankrd2), 68°C for 30 s (Desmin), 66°C for 30 s (Myogenin), or 69°C for 40 s [muscle LIM protein (MLP)], followed by a melt curve. Success of each reaction was deduced based on observing a single reaction product on an agarose gel and a single peak on the DNA melting temperature curve determined at the end of the reaction.
|
Statistical analysis.
Comparisons among genotypes were made with analysis of variance (ANOVA; Statview, SAS Institute), and a repeated-measures ANOVA was used when the same parameter was measured over time. Fisher's PLSD was used when ANOVA showed significant differences. Comparisons between the distribution of fiber types tested among genotypes for the single-fiber mechanical analysis were done with a 
2 analysis. P < 0.05 was considered to be significant, and all values are presented as means ± SE.
|
RESULTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
|---|
|
|
MKO muscles from both the soleus and the EDL had significantly longer titin lengths compared with wild-type controls (P < 0.01, Fig. 2E). No differences between genotypes were seen in any of the stress relaxation parameters, including peak stress, steady-state stress, or the time constants of decay during the 2-min hold after stretch (data not shown). In addition, there was no evidence of strain-softening behavior, because the tangent modulus did not change significantly between the first and second stretch cycle for any genotype.
Injury and recovery after ECs. No significant differences in the recovery of wild-type and MKO mice from EC-induced muscle injury when the same mice were followed over time were found by two-way ANOVA over time and between the two genotypes (Fig. 3A), indicating that the MARP family is not required for a normal recovery after injury. MKO mice showed a significantly greater degree of injury, however, as shown by the percentage drop from the initial torque produced by the muscle, immediately after the EC bout than wild-type mice (Fig. 3C). This greater injury was not a result of greater torque produced by and therefore borne by the muscle, because the initial torques were not significantly different between groups (Fig. 3B). No significant differences were seen with any of the other KO genotypes (Fig. 3, B and C). Torque loss and recovery after ECs was not significantly different when animals were subjected to the second protocol, with separate animals euthanized at each time point, as when they were subjected to the preliminary exercise protocol (Fig. 4A). It is unlikely that the increased injury seen in the MKO mice is due to increased fatigue susceptibility, because there was no difference between the response of MKO and wild-type mice to 50 isometric contractions (Fig. 4B). In addition, torque production in the contralateral legs of both genotypes was not significantly affected by the exercise protocol, suggesting that any differences between genotypes were not due to differential response to the stress of anesthesia or systemic exercise tolerance (Fig. 4C).
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
|---|
The passive mechanical data suggest that MARPs serve a structural role, such that in their absence skeletal muscle fibers are less stiff. The effect is subtle, and we did not detect it with the stretch to failure method (although there is a trend toward MKO being less stiff than wild type, Fig. 2A), which allows the fibers to stress-relax for 2 min before being stretched again. The viscoelastic phenomena that occur during these 2 min are complex and poorly understood, and it is possible that the absence of the MARPs has a small effect compared with the other mechanical events. When stretched at faster speeds, however, the absence of the MARPs was quite noticeable (Fig. 2, B and C), indicating that the MARPs play a role in regulating single muscle fiber stiffness. One possibility for how this regulation occurs is suggested by the data showing a longer resting sarcomere length in MKO mice compared with controls (Fig. 2D), which would directly result in the observed decrease in muscle fiber stiffness. The longer sarcomere length could be due to the expression of a longer isoform of titin in the triple MARP KO (Fig. 2E). Titin is the main molecule responsible for passive tension in striated muscle, and may be involved in setting resting sarcomere length. Different lengths of titin have been shown to be expressed in different tissues (34, 43), suggesting that there is precise, complex, and poorly understood regulation of titin isoform expression in skeletal muscle. These data suggest an intriguing connection between titin length expression and the MARP proteins.
In addition to altering the expression of titin isoforms, the MARPs may also have a mechanical contribution to passive tension, potentially mediated through their direct binding to the I band region of titin (26). In this scenario, the MARPs act to "clamp down" upon titin, perhaps stiffening it directly or tethering it more tightly to actin. When the MARPs are removed, therefore, titin would be somewhat more flexible, resulting in a decreased fiber tangent modulus. How the MARPs influence the length of titin and therefore the passive mechanical behavior of skeletal muscle fibers requires further testing.
In addition to the effect on in vitro passive mechanics, the larger than normal drop in torque after ECs (Fig. 3C) suggests that the MARPs may play a role in the stability of skeletal muscle under high active stress. The cause of decreased torque immediately after ECs is under much debate (35, 45), with explanations ranging from mechanical to neurological to energetic, and we are not certain of the cause of the decreased torque in our model. One obvious possibility for the large decrease in torque after exercise in the MKO mice compared with controls was increased fatigue. This is unlikely to be the case, however, because when the mice are exercised isometrically, which should be a larger metabolic load on the muscle than ECs, the drop in torque is if anything larger in wild-type than MKO mice (Fig. 4B). We are unaware of any role that the MARPs might play in excitation-contraction coupling. We believe, therefore, that it is most likely that the larger drop in torque after ECs in MKO mice is due to mechanical differences between the genotypes. The decreased passive tension, as described above, could be due to the absence of the MARPs causing titin instability and increased titin length. This instability could lead to increased sarcomere length inhomogeneity, which would result in a greater amount of damage to the fibers under high stress during EC, perhaps through increased numbers of "popped" sarcomeres (28). This would result in decreased torque immediately after exercise, as seen experimentally. Increased expression of this gene family after ECs would be consistent with their providing structural support for the muscle fiber: if absence of these genes leads to increased structural injury (i.e., sarcomere length instability), perhaps increased expression leads to protection from EC-induced injury. Further studies are required to test this hypothesis.
These data suggest that, in addition to their structural role, MARPs have a physiological influence on the gene expression program of skeletal muscle cells. The evidence for this is based on a number of observations. First, fiber type distribution in three different MKO muscles, the soleus, TA, and EDL, is shifted toward being more slow (Fig. 1, B–D). Although this shift was not statistically significant, the trend toward slower fiber type is consistent across all three muscles and is unusual, as fiber type distribution is usually quite invariant in mice (8). Fiber type is determined by a complicated set of genes, many of which are still being determined (5, 33, 36), and a shift in fiber type is suggestive of a fundamental change in the "thinking" of the muscle cell, either during development or in response to normal use. In addition, we have provided direct evidence that MKO mice have enhanced expression of two genes known to increase after ECs, keeping a similar time course of regulation known to occur after ECs (4, 32), MyoD and MLP. Both genes play an important positive role in either the regeneration of muscle (MyoD; Refs. 25, 47), or the response of skeletal muscle to exercise (MLP; Refs. 38, 46). Increased expression in the absence of the MARPs indicates that the MARPs have an inhibitory influence on these genes. Further evidence for this comes from the physiological response of the muscle to ECs: although the MKO mice showed greater injury (perhaps due to structural weakness resulting from the absence of MARPs), if anything they recovered faster and more completely from the injury compared with their wild-type counterparts (Fig. 3A; perhaps due to an enhanced gene expression response resulting from the absence of MARPs). Whether or not this increased recovery despite increased initial injury is due to increased MyoD and/or MLP expression remains unknown. The long-term effect of the absence of MARPs on muscle function after ECs is also unknown, because this study only examines changes that occur up to 9 days after injury.
The experiments presented here do not offer direct evidence as to how this influence on gene expression programs could occur. While it is possible that MARPs act directly as transcription inhibitors in the nucleus (19, 23, 48), this is not certain. Other possibilities include simply greater structural instability leading to greater transcription stimulation, or altered mechanical behavior of individual muscle fibers causing other stress sensors to transduce an altered gene expression message. In addition, the MARPs have at least two known binding partners in the sarcomere, titin and myopalladin (26), and there is some suggestion that even more interactions may occur (23). The extent of interconnectedness of various proteins within the sarcomere is immense (12), and it is therefore possible that the absence of the MARPs causes a general disorganization within the sarcomere, leading to altered gene expression among other effects.
It is interesting to speculate as to why normal muscle fiber would increase expression of this gene family in response to exercise, if it in fact inhibits the response to the exercise (4). There are examples in muscle physiology of phenomena having a short-term benefit but being detrimental in the long term, such as is possible with nonsteroidal anti-inflammatory drugs (27). In the absence of MARPs, while there seems to be a short-term increase in the expression of some genes involved with the regeneration of muscle and normal or possibly even enhanced functional torque recovery soon after injury, it is unknown whether MKO mice could show, for example, protection from injury due to ECs after training with ECs, or if they could show other normal training effects such as increased oxidative capacity or hypertrophy with exercise, all of which may require a more complicated and carefully regulated gene expression response. It is conceivable, for example, that the MARPs may help stimulate the immune response to injury. Without a robust immune response, the tissue would appear to recover faster than occurs with a complete response, but would not necessarily have a complete recovery at the cellular level and therefore might show a long-term deficit in function. It is also possible that the MARPs promote another beneficial response of the muscle to ECs that has not yet been determined, or that the increased expression of MARPs after EC is primarily due to the structural effects of this protein described above and the effect on gene expression is only secondary or is an epiphenomenon associated with the knockout model. More studies are needed to determine whether any of these possibilities are correct, because the studies presented here were limited to a single EC bout with torque measured only up to 9 days later.
The results presented here also offer some intriguing insights into how closely related the MARP family really is. While 50% homology is relatively high, the tissue distribution of the three MARPs is different (CARP highest in cardiac muscle, Ankrd2 and DARP in skeletal), and there is not any upregulation or compensation of the remaining MARP when one or more are removed (data not shown), at least at the mRNA level. The question of the functional homology of the three genes, therefore, remains unclear. All experiments except for the passive mechanics were performed on single KO of CARP, Ankrd2, and DARP and double KO of CARP and DARP or Ankrd2 and DARP, and yet the only significant changes were seen with the triple KO lacking all three proteins. There are two possible explanations for this phenomenon. The first is that the three proteins act independently from one another, and the phenotype of individual and double KO is too mild to be detected in our experiments. When all three are missing, however, a significant effect is seen. The second possibility is that the MARPs are, in fact, able to compensate for each other physiologically, such that it becomes necessary to remove all three in order to see an effect. Given that these three genes do have similar binding partners and intracellular distributions (26), the latter seems likely. It should be noted, however, that double KOs of CARP and Ankrd2 were not examined, and it therefore remains possible that only these two MARP family members compensate for each other. Given that only these genes, and not DARP, are upregulated after ECs (4), this remains a distinct possibility.
In summary, the MARP family plays an important role in the normal structure and function of skeletal muscle. Our data suggest that these genes are structural, providing stability within the sarcomere and protecting the muscle against EC-induced muscle injury, and perhaps also gene regulatory, modulating the expression of genes such as titin, MLP, and MyoD known to be important for the response of muscle to exercise and even the basal functioning of the muscle cell. Whether these effects are direct (i.e., direct transcriptional regulation) or indirect (i.e., resulting from structural instability leading to increased injury and therefore increased stimulation for gene expression or alterations in the behavior of MARP family binding partners) remains to be determined.
|
GRANTS |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
|---|
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|
REFERENCES |
|---|
|
TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
|---|
2. Bakay M, Zhao P, Chen J, Hoffman EP. A web-accessible complete transcriptome of normal human and DMD muscle. Neuromuscul Disord 12, Suppl 1: S125–S141, 2002.[CrossRef][ISI][Medline]
3. Bang ML, Mudry RE, McElhinny AS, Trombitas K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S. Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies. J Cell Biol 153: 413–427, 2001.
4. Barash IA, Mathew L, Ryan AF, Chen J, Lieber RL. Rapid muscle-specific gene expression changes after a single bout of eccentric contractions in the mouse. Am J Physiol Cell Physiol 286: C355–C364, 2004.
5. Bassel-Duby R, Olson EN. Role of calcineurin in striated muscle: development, adaptation, and disease. Biochem Biophys Res Commun 311: 1133–1141, 2003.[CrossRef][ISI][Medline]
7. Baumeister A, Arber S, Caroni P. Accumulation of muscle ankyrin repeat protein transcript reveals local activation of primary myotube endcompartments during muscle morphogenesis. J Cell Biol 139: 1231–1242, 1997.
8. Burkholder TJ, Fingado B, Baron S, Lieber RL. Relationship between muscle fiber types and sizes and muscle architectural properties in the mouse hindlimb. J Morphol 221: 177–190, 1994.[CrossRef][ISI][Medline]
9. Carson JA, Nettleton D, Reecy JM. Differential gene expression in the rat soleus muscle during early work overload-induced hypertrophy. FASEB J 16: 207–209, 2002.
10. Chen YW, Nader GA, Baar KR, Fedele MJ, Hoffman EP, Esser KA. Response of rat muscle to acute resistance exercise defined by transcriptional and translational profiling. J Physiol 545: 27–41, 2002.
11. Chu W, Burns DK, Swerlick RA, Presky DH. Identification and characterization of a novel cytokine-inducible nuclear protein from human endothelial cells. J Biol Chem 270: 10236–10245, 1995.
12. Clark KA, McElhinny AS, Beckerle MC, Gregorio CC. Striated muscle cytoarchitecture: an intricate web of form and function. Annu Rev Cell Dev Biol 18: 637–706, 2002.[CrossRef][ISI][Medline]
13. Eastwood AB, Wood DS, Bock KL, Sorenson MM. Chemically skinned mammalian skeletal muscle. I. The structure of skinned rabbit psoas. Tissue Cell 11: 553–566, 1979.[CrossRef][ISI][Medline]
14. Friden J, Lieber RL. Spastic muscle cells are shorter and stiffer than normal cells. Muscle Nerve 27: 157–164, 2003.[CrossRef][ISI][Medline]
15. Ikeda K, Emoto N, Matsuo M, Yokoyama M. Molecular identification and characterization of a novel nuclear protein whose expression is up-regulated in insulin-resistant animals. J Biol Chem 278: 3514–3520, 2003.
17. Ishiguro N, Baba T, Ishida T, Takeuchi K, Osaki M, Araki N, Okada E, Takahashi S, Saito M, Watanabe M, Nakada C, Tsukamoto Y, Sato K, Ito K, Fukayama M, Mori S, Ito H, Moriyama M. Carp, a cardiac ankyrin-repeated protein, and its new homologue, Arpp, are differentially expressed in heart, skeletal muscle, and rhabdomyosarcomas. Am J Pathol 160: 1767–1778, 2002.
18. Ishiguro N, Motoi T, Osaki M, Araki N, Minamizaki T, Moriyama M, Ito H, Yoshida H. Immunohistochemical analysis of a muscle ankyrin-repeat protein, Arpp, in paraffin-embedded tumors: evaluation of Arpp as a tumor marker for rhabdomyosarcoma. Hum Pathol 36: 620–625, 2005.[CrossRef][ISI][Medline]
19. Jeyaseelan R, Poizat C, Baker RK, Abdishoo S, Isterabadi LB, Lyons GE, Kedes L. A novel cardiac-restricted target for doxorubicin. CARP, a nuclear modulator of gene expression in cardiac progenitor cells and cardiomyocytes. J Biol Chem 272: 22800–22808, 1997.
20. Jones DA, Rutherford OM. Human muscle strength training: the effects of three different regimens and the nature of the resultant changes. J Physiol 391: 1–11, 1987.
21. Kemp TJ, Sadusky TJ, Saltisi F, Carey N, Moss J, Yang SY, Sassoon DA, Goldspink G, Coulton GR. Identification of Ankrd2, a novel skeletal muscle gene coding for a stretch-responsive ankyrin-repeat protein. Genomics 66: 229–241, 2000.[CrossRef][ISI][Medline]
22. Koh TJ, Brooks SV. Lengthening contractions are not required to induce protection from contraction-induced muscle injury. Am J Physiol Regul Integr Comp Physiol 281: R155–R161, 2001.
23. Kojic S, Medeot E, Guccione E, Krmac H, Zara I, Martinelli V, Valle G, Faulkner G. The Ankrd2 protein, a link between the sarcomere and the nucleus in skeletal muscle. J Mol Biol 339: 313–325, 2004.[CrossRef][ISI][Medline]
24. Kuo H, Chen J, Ruiz-Lozano P, Zou Y, Nemer M, Chien KR. Control of segmental expression of the cardiac-restricted ankyrin repeat protein gene by distinct regulatory pathways in murine cardiogenesis. Development 126: 4223–4234, 1999.[Abstract]
25. Megeney LA, Kablar B, Garrett K, Anderson JE, Rudnicki MA. MyoD is required for myogenic stem cell function in adult skeletal muscle. Genes Dev 10: 1173–1183, 1996.
26. Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S. The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules. J Mol Biol 333: 951–964, 2003.[CrossRef][ISI][Medline]
27. Mishra DK, Friden J, Schmitz MC, Lieber RL. Anti-inflammatory medication after muscle injury. A treatment resulting in short-term improvement but subsequent loss of muscle function. J Bone Joint Surg Am 77: 1510–1519, 1995.
28. Morgan DL. New insights into the behavior of muscle during active lengthening. Biophys J 57: 209–221, 1990.[Medline]
29. Nakada C, Oka A, Nonaka I, Sato K, Mori S, Ito H, Moriyama M. Cardiac ankyrin repeat protein is preferentially induced in atrophic myofibers of congenital myopathy and spinal muscular atrophy. Pathol Int 53: 653–658, 2003.[CrossRef][ISI][Medline]
30. Nakada C, Tsukamoto Y, Oka A, Nonaka I, Sato K, Mori S, Ito H, Moriyama M. Altered expression of ARPP protein in skeletal muscles of patients with muscular dystrophy, congenital myopathy and spinal muscular atrophy. Pathobiology 71: 43–51, 2004.[CrossRef][ISI][Medline]
31. Newham DJ, Jones DA, Clarkson PM. Repeated high-force eccentric exercise: effects on muscle pain and damage. J Appl Physiol 63: 1381–1386, 1987.
32. Peters D, Barash IA, Burdi M, Yuan PS, Mathew L, Friden J, Lieber RL. Asynchronous functional, cellular and transcriptional changes after a bout of eccentric exercise in the rat. J Physiol 553: 947–957, 2003.
33. Pette D. Plasticity of mammalian skeletal muscle. J Appl Physiol 90: 1119–1124, 2001.
34. Prado LG, Makarenko I, Andresen C, Kruger M, Opitz CA, Linke WA. Isoform diversity of giant proteins in relation to passive and active contractile properties of rabbit skeletal muscles. J Gen Physiol 126: 461–480, 2005.
35. Proske U, Morgan DL. Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications. J Physiol 537: 333–345, 2001.
36. Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24: 78–90, 2003.
37. Sacco P, Jones DA. The protective effect of damaging eccentric exercise against repeated bouts of exercise in the mouse tibialis anterior muscle. Exp Physiol 77: 757–760, 1992.[Abstract]
38. Schneider AG, Sultan KR, Pette D. Muscle LIM protein: expressed in slow muscle and induced in fast muscle by enhanced contractile activity. Am J Physiol Cell Physiol 276: C900–C906, 1999.
39. Schwane JA, Armstrong RB. Effect of training on skeletal muscle injury from downhill running in rats. J Appl Physiol 55: 969–975, 1983.
40. Sosnicki AA, Lutz GJ, Rome LC, Goble DO. Histochemical and molecular determination of fiber types in chemically skinned single equine skeletal muscle fibers. J Histochem Cytochem 37: 1731–1738, 1989.[Abstract]
41. Talmadge RJ, Roy RR. Electrophoretic separation of rat skeletal muscle myosin heavy-chain isoforms. J Appl Physiol 75: 2337–2340, 1993.
42. Tsukamoto Y, Senda T, Nakano T, Nakada C, Hida T, Ishiguro N, Kondo G, Baba T, Sato K, Osaki M, Mori S, Ito H, Moriyama M. Arpp, a new homolog of carp, is preferentially expressed in type 1 skeletal muscle fibers and is markedly induced by denervation. Lab Invest 82: 645–655, 2002.[CrossRef][ISI][Medline]
43. Warren CM, Krzesinski PR, Campbell KS, Moss RL, Greaser ML. Titin isoform changes in rat myocardium during development. Mech Dev 121: 1301–1312, 2004.[CrossRef][ISI][Medline]
44. Warren CM, Krzesinski PR, Greaser ML. Vertical agarose gel electrophoresis and electroblotting of high-molecular-weight proteins. Electrophoresis 24: 1695–1702, 2003.[CrossRef][ISI][Medline]
45. Warren GL, Ingalls CP, Lowe DA, Armstrong RB. Excitation-contraction uncoupling: major role in contraction-induced muscle injury. Exerc Sport Sci Rev 29: 82–87, 2001.[CrossRef][Medline]
46. Willmann R, Kusch J, Sultan KR, Schneider AG, Pette D. Muscle LIM protein is upregulated in fast skeletal muscle during transition toward slower phenotypes. Am J Physiol Cell Physiol 280: C273–C279, 2001.
47. Yablonka-Reuveni Z, Rudnicki MA, Rivera AJ, Primig M, Anderson JE, Natanson P. The transition from proliferation to differentiation is delayed in satellite cells from mice lacking MyoD. Dev Biol 210: 440–455, 1999.[CrossRef][ISI][Medline]
48. Zou Y, Evans S, Chen J, Kuo HC, Harvey RP, Chien KR. CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway. Development 124: 793–804, 1997.[Abstract]
This article has been cited by other articles:
|
|
 |
|
  J. Zhang, M.-L. Bang, D. S. Gokhin, Y. Lu, L. Cui, X. Li, Y. Gu, N. D. Dalton, M. C. Scimia, K. L. Peterson, et al. Syncoilin is required for generating maximum isometric stress in skeletal muscle but dispensable for muscle cytoarchitecture Am J Physiol Cell Physiol, May 1, 2008; 294(5): C1175 - C1182. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP |
