Extracellular signal-regulated kinase pathway is differentially involved in beta-agonist-induced hypertrophy in slow and fast muscles

The molecular mechanisms controlling -adrenergic receptor agonist (BA)-induced skeletal muscle hypertrophy are not well known. We presently report that BA exerts a distinct muscle- and muscle fiber type-specific hypertrophy. Moreover, we have shown that pharmacologically or genetically attenuating extracellular signal-regulated kinase (ERK) signaling in muscle fibers resulted in decreases (P < 0.05) in fast but not slow fiber type-specific reporter gene expressions in response to BA exposure in vitro and in vivo. Consistent with these data, forced expression of MAPK phosphatase 1, a nuclear protein that dephosphorylates ERK1/2, in fast-twitch skeletal muscle ablated (P < 0.05) the hypertrophic effects of BA feeding (clenbuterol, 20 parts per million in water) in vivo. Further analysis has shown that BA-induced phosphorylation and activation of ERK occurred to a greater (P < 0.05) extent in fast myofibers than in slow myofibers. Analysis of the basal level of ERK activity in slow and fast muscles revealed that ERK1/2 is activated to a greater extent in fast- than in slow-twitch muscles. These data indicate that ERK signaling is differentially involved in BA-induced hypertrophy in slow and fast skeletal muscles, suggesting that the increased abundance of phospho-ERK1/2 and ERK activity found in fast-twitch myofibers, compared with their slow-twitch counterparts, may account, at least in part, for the fiber type-specific hypertrophy induced by BA stimulation. These data suggest that fast myofibers are pivotal in the adaptation of muscle to environmental cues and that the mechanism underlying this change is partially mediated by the MAPK signaling cascade. muscle fiber type; mitogen-activated protein kinase signaling pathways; mechanism     

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

Delp, Michael D., Changping Duan, John P. Mattson, andTimothy I. Musch. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure.J. Appl. Physiol. 83(4):1291-1299, 1997.One of the primary consequences of leftventricular dysfunction (LVD) after myocardial infarction is adecrement in exercise capacity. Several factors have been hypothesizedto account for this decrement, including alterations in skeletal musclemetabolism and aerobic capacity. The purpose of this study was todetermine whether LVD-induced alterations in skeletal muscle enzymeactivities, fiber composition, and fiber size are1) generalized in muscles orspecific to muscles composed primarily of a given fiber type and2) related to the severity of theLVD. Female Wistar rats were divided into three groups: sham-operatedcontrols (n = 13) and rats withmoderate (n = 10) and severe(n = 7) LVD. LVD was surgicallyinduced by ligating the left main coronary artery and resulted inelevations (P < 0.05) in leftventricular end-diastolic pressure (sham, 5 ± 1 mmHg; moderate LVD,11 ± 1 mmHg; severe LVD, 25 ± 1 mmHg). Moderate LVDdecreased the activities of phosphofructokinase (PFK) and citratesynthase in one muscle composed of type IIB fibers but did not modifyfiber composition or size of any muscle studied. However, severe LVDdiminished the activity of enzymes involved in terminal and-oxidation in muscles composed primarily of type I fibers, type IIAfibers, and type IIB fibers. In addition, severe LVD induced areduction in the activity of PFK in type IIB muscle, a 10% reductionin the percentage of type IID/X fibers, and a corresponding increase inthe portion of type IIB fibers. Atrophy of type I fibers, type IIAfibers, and/or type IIB fibers occurred in soleus and plantarismuscles of rats with severe LVD. These data indicate that rats withsevere LVD after myocardial infarction exhibit1) decrements in mitochondrialenzyme activities independent of muscle fiber composition,2) a reduction in PFK activity in type IIB muscle, 3) transformationof type IID/X to type IIB fibers, and4) atrophy of type I, IIA, and IIBfibers.

     

Skeletal muscle adaptation in response to voluntary running in Ca2+/calmodulin-dependent protein kinase IV-deficient mice

Mammalian skeletal muscles undergo adaptation in response to alteration in functional demands by means of a variety of cellular signaling events. Previous experiments in transgenic mice showed that an active form of Ca²⁺/calmodulin-dependent protein kinase IV (CaMKIV) is capable of stimulating peroxisome proliferator-activated receptor -coactivator 1 (PGC-1) gene expression, promoting fast-to-slow fiber type switching and augmenting mitochondrial biogenesis in skeletal muscle. However, a role for endogenous CaMKIV in skeletal muscle has not been investigated rigorously. We report that genetically modified mice devoid of CaMKIV have normal fiber type composition and mitochondrial enzyme expression in fast-twitch skeletal muscles and responded to long-term (4 wk) voluntary running with increased expression of myosin heavy chain type IIa, myoglobin, PGC-1, and cytochrome c oxidase IV proteins in plantaris muscle in a manner similar to that of wild-type mice. Short-term motor nerve stimulation (2 h at 10 Hz) likewise increased PGC-1 mRNA expression in tibialis anterior muscles in both Camk4^–/– and wild-type mice. In addition, we have confirmed that no detectable CaMKIV protein is expressed in murine skeletal muscle. Thus CaMKIV is not required for the maintenance of slow-twitch muscle phenotype and endurance training-induced mitochondrial biogenesis and IIb-to-IIa fiber type switching in murine skeletal muscle. Other protein kinases sharing substrates with constitutively active CaMKIV may function as endogenous mediators of activity-dependent changes in myofiber phenotype. cellular signaling; proliferator-activated receptor -coactivator 1; fiber type switching; mitochondrial biogenesis     

Responses of group III and IV muscle afferents to dynamic exercise

Adreani, Christine M., Janeen M. Hill, and Marc P. Kaufman.Responses of group III and IV muscle afferents to dynamic exercise. J. Appl. Physiol. 82(6):1811-1817, 1997.Tetanic contraction of hindlimb skeletal muscle,induced by electrical stimulation of either ventral roots or peripheralnerves, is well known to activate group III and IV afferents.Nevertheless, the effect of dynamic exercise on the discharge of thesethin fiber afferents is unknown. To shed some light on this question,we recorded in decerebrate cats the discharge of 24 group III and 10 group IV afferents while the mesencephalic locomotor region (MLR) wasstimulated electrically. Each of the 34 afferents had their receptivefields in the triceps surae muscles. Stimulation of the MLR for 1 min caused the triceps surae muscles to contract rhythmically, an effectinduced by an -motoneuron discharge pattern and recruitment orderalmost identical to that occurring during dynamic exercise. Eighteen ofthe 24 group III and 8 of the 10 group IV muscle afferents werestimulated by MLR stimulation. The oxygen consumption of thedynamically exercising triceps surae muscles was increased by 2.5-foldover their resting levels. We conclude that low levels of dynamicexercise stimulate group III and IV muscle afferents.

     

Modulation of myosin isoform expression by mechanical loading: role of stimulation frequency

Caiozzo, Vincent J., Michael J. Baker, and Kenneth M. Baldwin. Modulation of myosin isoform expression by mechanical loading: role of stimulation frequency. J. Appl.Physiol. 82(1): 211-218, 1997.This study testedthe hypothesis that mechanical loading, not stimulation frequency perse, plays a key role in determining the plasticity of myosin heavychain (MHC) protein isoform expression in muscle undergoing resistancetraining. Female Sprague-Dawley rats were randomly assigned toresistance-training programs that employed active1) shortening(n = 7) or2) lengthening contractions(n = 8). The medial gastrocnemius (MG)muscles in each group trained under loading conditions thatapproximated 90-95% of maximum isometric tetanictension but were stimulated at frequencies of 100 and~25 Hz, respectively. Lengthening and shortening contractions wereproduced by using a Cambridge ergometer system. The MG muscles trainedevery other day, performing a total of 16 training sessions. Bothtraining programs produced significant (P < 0.01) and similar reductions inthe fast type IIB MHC protein isoform in the white MG muscle, reducingits relative content to ~50% of the total MHC protein isoform pool.These changes were accompanied by increases in the relative content ofthe fast type IIX MHC protein isoform that were of similar magnitudefor both groups. The results of this study clearly demonstrate thatstimulation frequency does not play a key role in modulating MHCisoform alterations that result from high-resistance training.

     

Evidence that nitric oxide increases glucose transport in skeletal muscle

Balon, Thomas W., and Jerry L. Nadler. Evidence thatnitric oxide increases glucose transport in skeletal muscle.J. Appl. Physiol. 82(1): 359-363, 1997.Nitric oxide synthase (NOS) is expressed in skeletal muscle.However, the role of nitric oxide (NO) in glucose transport in thistissue remains unclear. To determine the role of NO in modulatingglucose transport, 2-deoxyglucose (2-DG) transport was measured in ratextensor digitorum longus (EDL) muscles that were exposed to either amaximally stimulating concentration of insulin or to an electricalstimulation protocol, in the presence ofN^G-monomethyl-L-arginine,a NOS inhibitor. In addition, EDL preparations were exposed to sodiumnitroprusside (SNP), an NO donor, in the presence of submaximal andmaximally stimulating concentrations of insulin. NOS inhibition reducedboth basal and exercise-enhanced 2-DG transport but had no effect oninsulin-stimulated 2-DG transport. Furthermore, SNP increased 2-DGtransport in a dose-responsive manner. The effects of SNP and insulinon 2-DG transport were additive when insulin was present inphysiological but not in pharmacological concentrations. Chronictreadmill training increased protein expression of both type I and typeIII NOS in soleus muscle homogenates. Our results suggest that NO maybe a potential mediator of exercise-induced glucose transport.

     

Expression of nitric oxide synthase isoforms in normal ventilatory and limb muscles

Hussain, Sabah N. A., Qasim El-Dwairi, Mohammed N. Abdul-Hussain, and Dalia Sakkal. Expression of nitric oxidesynthase isoforms in normal ventilatory and limb muscles.J. Appl. Physiol. 83(2): 348-353, 1997.Nitric oxide (NO), an important messenger molecule withwidespread actions, is synthesized by NO synthases (NOS). In thisstudy, we investigated the correlation between fiber type and NOSactivity among ventilatory and limb muscles of various species. We alsoassessed the presence of the three NOS isoforms in normal skeletalmuscles and how various NOS inhibitors influence muscle NOS activity.NOS activity was detected in various muscles; however, NOS activity inrabbits and rats varied significantly among different muscles.Immunoblotting of muscle samples indicated the presence of both theneuronal NOS and the endothelial NOS isoforms but not thecytokine-inducible NOS isoform. However, these isoforms were expressedto different degrees in various muscles. Although the neuronal NOSisoform was detectable in the canine diaphragm, very weak expressionwas detected in rabbit, rat, and mouse diaphragms. The endothelial NOSisoform was detected in the rat and mouse diaphragms but not in thecanine and rabbit diaphragms. We also found thatN^G-nitro-L-arginine methyl ester,7-nitroindazole, andS-methylisothiourea werestronger inhibitors of muscle NOS activity than was aminoguanidine. These results indicate the presence of different degrees ofconstitutive NOS expression in normal ventilatory and limb muscles ofvarious species. Our data also indicate that muscle NOS activity is not determined by fiber type distribution but by other not yet identified factors. The functional significance of this expression remains to beassessed.

     

Mechanical properties of rabbit latissimus dorsi muscle after stretch and/or electrical stimulation

James, R. S., V. M. Cox, I. S. Young, J. D. Altringham, andD. F. Goldspink Mechanical properties of rabbit latissimus dorsimuscle after stretch and/or electrical stimulation.J. Appl. Physiol. 83(2): 398-406, 1997.The work loop technique was used to measure the mechanicalperformance in situ of the latissimus dorsi (LD) muscles of rabbitsmaintained under fentanyl anesthesia. After 3 wk of incrementallyapplied stretch the LD muscles were 36% heavier, but absolute poweroutput (195 mW/muscle) was not significantly changed relative to thatof external control muscle (206 mW). In contrast, continuous 10-Hzelectrical stimulation reduced power output per kilogram of muscle>75% after 3 or 6 wk and muscle mass by 32% after 6 wk. Whencombined, stretch and 10-Hz electrical stimulation preserved orincreased the mass of the treated muscles but failed to prevent an 80%loss in maximum muscle power. However, this combined treatmentincreased fatigue resistance to a greater degree than electricalstimulation alone. These stretched/stimulated muscles, therefore, aremore suitable for cardiomyoplasty. Nonetheless, further work will benecessary to find an ideal training program for this surgicalprocedure.

     

Expression of the inducible nitric oxide synthase gene in diaphragm and skeletal muscle

Thompson, Marita, Lisa Becker, Debbie Bryant, Gary Williams,Daniel Levin, Linda Margraf, and Brett P. Giroir. Expression ofthe inducible nitric oxide synthase gene in diaphragm and skeletal muscle. J. Appl. Physiol. 81(6):2415-2420, 1996.Nitric oxide (NO) is a pluripotent molecule thatcan be secreted by skeletal muscle through the activity of the neuronalconstitutive isoform of NO synthase. To determine whether skeletalmuscle and diaphragm might also express the macrophage-inducible formof NO synthase (iNOS) during provocative states, we examined tissuefrom mice at serial times after intravenous administration ofEscherichia coli endotoxin. In thesestudies, iNOS mRNA was strongly expressed in the diaphragm and skeletalmuscle of mice 4 h after intravenous endotoxin and was significantlydiminished by 8 h after challenge. Induction of iNOS mRNA was followedby expression of iNOS immunoreactive protein on Western immunoblots.Increased iNOS activity was demonstrated by conversion of arginine tocitrulline. Immunochemical analysis of diaphragmatic explants exposedto endotoxin in vitro revealed specific iNOS staining in myocytes, inaddition to macrophages and endothelium. These results may be importantin understanding the pathogenesis of respiratory pump failure duringseptic shock, as well as skeletal muscle injury during inflammation ormetabolic stress.

     

Decreased insulin action on muscle glucose transport after eccentric contractions in rats

Asp, Sven, and Erik A. Richter. Decreased insulinaction on muscle glucose transport after eccentric contractions in rats. J. Appl. Physiol. 81(5):1924-1928, 1996.We have recently shown that eccentriccontractions (Ecc) of rat calf muscles cause muscle damage anddecreased glycogen and glucose transporter GLUT-4 protein content inthe white (WG) and red gastrocnemius (RG) but not in the soleus (S) (S. Asp, S. Kristiansen, and E. A. Richter. J. Appl.Physiol. 79: 1338-1345, 1995). To study whetherthese changes affect insulin action, hindlimbs were perfused at three different insulin concentrations (0, 200, and 20,000 µU/ml) 2 daysafter one-legged eccentric contractions of the calf muscles. Comparedwith control, basal glucose transport was slightly higher (P < 0.05) in Ecc-WG and -RG,whereas it was lower (P < 0.05) atboth submaximal and maximal insulin concentrations in the Ecc-WG and atmaximal concentrations in the Ecc-RG. In the Ecc-S, the glucosetransport was unchanged in hindquarters perfused in the absence orpresence of a submaximal stimulating concentration of insulin, whereasit was slightly (P < 0.05) higherduring maximal insulin stimulation compared with control S. At the endof perfusion the glycogen concentrations were lower in bothEcc-gastrocnemius muscles compared with control muscles at all insulinconcentrations. Fractional velocity of glycogen synthase increasedsimilarly with increasing insulin concentrations in Ecc- and control WGand RG. We conclude that insulin action on glucose transport but notglycogen synthase activity is impaired in perfused muscle exposed toprior eccentric contractions.

     

Regional blood flows in the goat latissimus dorsi muscle before and after chronic stimulation

Klabunde, Richard E., William A. Anderson, Marius Locke,Sigrid E. Ianuzzo, and C. David Ianuzzo. Regional blood flows inthe goat latissimus dorsi muscle before and after chronic stimulation. J. Appl. Physiol. 81(6):2365-2372, 1996.Latissimus dorsi muscle (LDM) regional bloodflows were determined in anesthetized goats by using coloredmicrospheres under noncontracting and contracting conditions, eitherbefore or after 8-10 wk of chronic muscle stimulation. Surgicaldissection of the LDM, leaving only the thoracodorsal artery to supplythe muscle, did not alter regional noncontracting blood flows butsignificantly reduced the normal hyperemic response to musclecontraction in muscle regions (posterior-medial) furthest from theentrance of the thoracodorsal artery. Eight to 10 wk after acute muscledissection, posterior-medial hyperemic flows were restored. Chronicstimulation of the LDM for 8-10 wk, in either dissected ornondissected muscles, did not alter regional blood flows innoncontracting muscle; however, it significantly reduced hyperemicflows in all muscle regions, although capillary density was increasedand the muscle was transformed into a predominantly type I fiber type.These results, coupled with data from previous experiments, suggestthat the muscle damage observed in the posterior-medial regions of theLDM after surgical dissection and chronic stimulation may be related toreduced hyperemic flow responses caused by surgical isolation of themuscle.

     

Time course of recovery from nerve injury in skeletal muscle: energy state and local circulation

Hayashi, Yoshihiro, Takaaki Ikata, Hiroaki Takai, ShinjiroTakata, Takayuki Sogabe, and Keiko Koga. Time course of recoveryfrom nerve injury in skeletal muscle: energy state and localcirculation. J. Appl. Physiol. 82(3):732-737, 1997.This study examined the time course of recoveryfrom nerve injury on energy state assessed by phosphorus-31 magneticresonance spectroscopy and local circulation dynamics by fluorine-19magnetic resonance spectroscopy in skeletal muscles ofrats. The hindlimb muscles that had undergone unilateralsciatic nerve compression for 2 wk (CN) were compared withsham-operated (SO) muscles and with muscles that had the compressionremoved after 2 wk and were allowed to recover for 4 wk (R4) or for 6 wk (R6). The energy state and local circulation dynamics of CN muscleswere less than those of SO muscles (P < 0.01). The energy state of R4 muscles remained at levels similar toCN muscles, whereas the local circulation dynamics improved but notback to SO values. In R6 muscles, both parameters returned to SOvalues. These results showed that the recovery processes of circulationprecede those of energy state in skeletal muscles.

     

Variable-frequency train stimulation of canine latissimus dorsi muscle during shortening contractions

George, David T., Stuart A. Binder-Macleod, Thomas N. Delosso, and William P. Santamore. Variable-frequency trainstimulation of canine latissimus dorsi muscle during shorteningcontractions. J. Appl. Physiol. 83(3):994-1001, 1997.In cardiomyoplasty, the latissimus dorsi muscle(LDM) is wrapped around the heart ventricles and electrically activatedwith a constant-frequency train (CFT). This study tested the hypothesesthat increased mechanical performance from the LDM could be achieved byactivating the muscle with variable-frequency trains (VFTs) of shorterduration or containing fewer stimulus pulses than the CFT now used. Themechanical performance of the canine LDM (n = 7) during shortening contractionswas measured while the muscle was stimulated with 5- and 6-pulse CFTs(of duration 132 and 165 ms, respectively) and 5- and 6-pulse VFTs (ofduration 104 and 143 ms, respectively) that were designed to takeadvantage of the catchlike property of skeletal muscle. Measurementswere made from fresh and fatigued muscles. For the fresh muscles, the VFTs elicited significantly greater peak power than did the 6-pulse CFT. When the muscles were fatigued, VFT stimulation significantly improved both the peak and mean power produced compared withstimulation by CFTs. These results show that stimulation of the LDMwith shorter duration VFTs is potentially useful for application incardiomyoplasty.

     

Prior eccentric contractions impair maximal insulin action on muscle glucose uptake in the conscious rat

Asp, Sven, Allan Watkinson, Nicholas D. Oakes, and Edward W. Kraegen. Prior eccentric contractions impair maximal insulin action on muscle glucose uptake in the conscious rat.J. Appl. Physiol. 82(4):1327-1332, 1997.Our aim was to examine the effect of prioreccentric contractions on insulin action locally in muscle in theintact conscious rat. Anesthetized rats performed one-leg eccentriccontractions through the use of calf muscle electrical stimulationfollowed by stretch of the active muscles. Two days later, basal andeuglycemic clamp studies were conducted with the rats in the awakefasted state. Muscle glucose metabolism was estimated from2-[¹⁴C(U)]deoxy-D-glucoseandD-[3-³H]glucose administration, and comparisons were made between the eccentrically stimulated and nonstimulated (control) calfmuscles. At midphysiological insulin levels, effects ofprior eccentric exercise on muscle glucose uptake were notstatistically significant. Maximal insulin stimulation revealed reducedincremental glucose uptake above basal(P < 0.05 in the red gastrocnemius;P < 0.1 in the white gastrocnemiusand soleus) and impaired net glycogen synthesis in all eccentricallystimulated muscles (P < 0.05). Weconclude that prior eccentric contractions impair maximal insulin action (responsiveness) on local muscle glucose uptake and glycogen synthesis in the conscious rat.

     

Oxidation of lactate and acetate in rat skeletal muscle: analysis by 13C-nuclear magnetic resonance spectroscopy

Bertocci, Loren A., John G. Jones, Craig R. Malloy, RonaldG. Victor, and Gail D. Thomas. Oxidation of lactateand acetate in rat skeletal muscle: analysis by¹³C-nuclear magnetic resonancespectroscopy. J. Appl. Physiol. 83(1): 32-39, 1997.The balance between carbohydrate and fatty acidutilization in skeletal muscle previously has been studied in vivo byusing a variety of methods such as arteriovenous concentrationdifferences and radioactive isotope tracer techniques. However, thesemethodologies provide only indirect estimates of substrate oxidation.We used ¹³C-nuclear magneticresonance (NMR) spectroscopy and non-steady-state isotopomer analysisto directly quantify the relative oxidation of two competing exogenoussubstrates in rat skeletal muscles. We infused[1,2-¹³C]acetate and[3-¹³C]lactateintravenously in anesthetized rats during the final 30 min of 35 (n = 10) or 95 (n = 10) min of intense, unilateral, rhythmic hindlimb contractions.¹³C-NMR spectroscopy andisotopomer analysis were performed on extracts of gastrocnemius andsoleus muscles from both the contracting and contralateralresting hindlimbs. We found that1)[¹³C]lactate and[¹³C]acetate were taken up and oxidized by both restingand contracting skeletal muscles; and2) high-intensity musclecontractions altered the pattern of substrate utilization such that therelative oxidation of acetate decreased while that of lactate remainedunchanged or increased. Based on these findings, we propose that¹³C-NMR spectroscopy incombination with isotopomer analysis can be used to study the generaldynamics of substrate competition between carbohydrates and fats in ratskeletal muscle.

     

Long-term facilitation of upper airway muscle activities in vagotomized and vagally intact cats

Mateika, J. H., and R. F. Fregosi. Long-termfacilitation of upper airway muscle activities in vagotomized andvagally intact cats. J. Appl. Physiol.82(2): 419-425, 1997.The primary purpose of the presentinvestigation was to determine whether long-term facilitation (LTF) ofupper airway muscle activities occurs in vagotomized and vagally intactcats. Tidal volume and diaphragm, genioglossus, and nasal dilatormuscle activities were recorded before, during, and after one carotidsinus nerve was stimulated five times with 2-min trains of constantcurrent. Sixty minutes after stimulation, nasal dilator andgenioglossus muscle activities were significantly greater than controlin the vagotomized cats but not in the vagally intact cats. Tidalvolume recorded from the vagotomized and vagally intact cats wassignificantly greater than control during the poststimulation period.In contrast, diaphragm activities were not significantly elevated inthe poststimulation period in either group of animals. We conclude that1) LTF of genioglossus and nasaldilator muscle activities can be evoked in vagotomized cats;2) vagal mechanisms inhibit LTF inupper airway muscles; and 3) LTF canbe evoked in accessory inspiratory muscles because LTF of inspiredtidal volume was greater than LTF of diaphragm activity.

     

Effect of microgravity on the expression of mitochondrial enzymes in rat cardiac and skeletal muscles

Connor, Michael K., and David A. Hood. Effect ofmicrogravity on the expression of mitochondrial enzymes in rat cardiac and skeletal muscles. J. Appl.Physiol. 84(2): 593-598, 1998.The purpose ofthis study was to examine the expression of nuclear and mitochondrialgenes in cardiac and skeletal muscle (triceps brachii) in response toshort-duration microgravity exposure. Six adult male rats were exposedto microgravity for 6 days and were compared with six ground-basedcontrol animals. We observed a significant 32% increase in heartmalate dehydrogenase (MDH) enzyme activity, which was accompanied by a62% elevation in heart MDH mRNA levels after microgravity exposure.Despite modest elevations in the mRNAs encoding subunits III, IV, andVIc as well as a 2.2-fold higher subunit IV protein content afterexposure to microgravity, heart cytochromec oxidase (CytOx) enzyme activityremained unchanged. In skeletal muscle, MDH expression was unaffectedby microgravity, but CytOx activity was significantly reduced 41% bymicrogravity, whereas subunit III, IV, and VIc mRNA levels and subunitIV protein levels were unaltered. Thus tissue-specific (i.e., heart vs.skeletal muscle) differences exist in the regulation of nuclear-encoded mitochondrial proteins in response to microgravity. In addition, theexpression of nuclear-encoded proteins such as CytOx subunit IV andexpression of MDH are differentially regulated within a tissue. Ourdata also illustrate that the heart undergoes previously unidentifiedmitochondrial adaptations in response to short-term microgravityconditions more dramatic than those evident in skeletal muscle. Furtherstudies evaluating the functional consequences of these adaptations inthe heart, as well as those designed to measure protein turnover, arewarranted in response to microgravity.

     

The relationships among IGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy

Adams, G. R., and F. Haddad. The relationships amongIGF-1, DNA content, and protein accumulation during skeletal muscle hypertrophy. J. Appl. Physiol. 81(6):2509-2516, 1996.Insulin-like growth factor-1 (IGF-1) is known tohave anabolic effects on skeletal muscle cells. This study examined thetime course of muscle hypertrophy and associated IGF-1 peptide and mRNAexpression. Data were collected at 3, 7, 14, and 28 days after surgicalremoval of synergistic muscles of both normal and hypophysectomized(HX) animals. Overloading increased the plantaris (Plant) mass,myofiber size, and protein-to-body weight ratio in both groups (normaland HX; P < 0.05). Muscle IGF-1peptide levels peaked at 3 (normal) and 7 (HX) days of overloading withmaximum 4.1-fold (normal) and 6.2-fold (HX) increases. Increases inmuscle IGF-1 preceded the hypertrophic response. Total DNA content ofthe overloaded Plant increased in both groups. There was a strongpositive relationship between IGF-1 peptide and DNA content in theoverloaded Plant from both groups. These results indicate that1) the muscles from rats with bothnormal and severely depressed systemic levels of IGF-1 respond tofunctional overload with an increase in local IGF-1 expression and2) this elevated IGF-1 may becontributing to the hypertrophy response, possibly via the mobilizationof satellite cells to provide increases in muscle DNA.

     

Endurance training affects myosin heavy chain phenotype in regenerating fast-twitch muscle

Bigard, Xavier A., Chantal Janmot, Danièle Merino,Françoise Lienhard, Yannick C. Guezennec, and Anne D'Albis.Endurance training affects myosin heavy chain phenotype inregenerating fast-twitch muscle. J. Appl.Physiol. 81(6): 2658-2665, 1996.The aim of thisstudy was to analyze the effects of treadmill training (2 h/day, 5 days/wk, 30 m/min, 7% grade for 5 wk) on the expression of myosinheavy chain (MHC) isoforms during and after regeneration of afast-twitch white muscle [extensor digitorum longus (EDL)]. Male Wistar rats were randomly assigned to a sedentary(n = 10) or an endurance-trained (ET;n = 10) group. EDL muscle degeneration and regeneration were induced by two subcutaneous injections of a snaketoxin. Five days after induction of muscle injury, animals were trainedover a 5-wk period. It was verified that ~40 days after venomtreatment, central nuclei were present in the treated EDL muscles fromsedentary and ET rats. The changes in the expression of MHCs in EDLmuscles were detected by using a combination of biochemical andimmunocytochemical approaches. Compared with contralateral nondegenerated muscles, relative concentrations of types I, IIa, andIIx MHC isoforms in ET rats were greater in regenerated EDL muscles(146%, P < 0.05; 76%,P < 0.01; 87%,P < 0.01, respectively). Their elevation corresponded to a decreasein the relative concentration of type IIb MHC (36%,P < 0.01). Although type I accountedfor only 3.2% of total myosin in regenerated muscles from the ETgroup, the cytochemical analysis showed that the proportion of positive staining with the slow MHC antibody was markedly greater in regenerated muscles than in contralateral ones. Collectively, these results demonstrate that the regenerated EDL muscle is sensitive to endurance training and suggest that the training-induced shift in MHC isoforms observed in these muscles resulted from an additive effect of regeneration and repeated exercise.