Research Interests:
Spaceflight causes muscle wasting. The Sarcolab pilot study investigated two astronauts with regards to plantar flexor muscle size, architecture, and function, and to the underlying molecular adaptations in order to further the... more
Spaceflight causes muscle wasting. The Sarcolab pilot study investigated two astronauts with regards to plantar flexor muscle size, architecture, and function, and to the underlying molecular adaptations in order to further the understanding of muscular responses to spaceflight and exercise countermeasures. Two crew members (A and B) spent 6 months in space. Crew member A trained less vigorously than B. Postflight, A showed substantial decrements in plantar flexor volume, muscle architecture, in strength and in fiber contractility, which was strongly mitigated in B. The difference between these crew members closely reflected FAK-Y397 abundance, a molecular marker of muscle’s loading history. Moreover, crew member A showed downregulation of contractile proteins and enzymes of anaerobic metabolism, as well as of systemic markers of energy and protein metabolism. However, both crew members exhibited decrements in muscular aerobic metabolism and phosphate high energy transfer. We conclu...
Research Interests:
Research Interests:
Skeletal muscle atrophy occurs as a result of disuse. Although several studies have established that a decrease in protein synthesis and increase in protein degradation lead to muscle atrophy, little is known about the triggers underlying... more
Skeletal muscle atrophy occurs as a result of disuse. Although several studies have established that a decrease in protein synthesis and increase in protein degradation lead to muscle atrophy, little is known about the triggers underlying such processes. A growing body of evidence challenges oxidative stress as a trigger of disuse atrophy; furthermore, it is also becoming evident that mitochondrial dysfunction may play a causative role in determining muscle atrophy. Mitochondrial fusion and fission have emerged as important processes that govern mitochondrial function and PGC-1α may regulate fusion/fission events. Although most studies on mice have focused on the anti-gravitary slow soleus muscle as it is preferentially affected by disuse atrophy, several fast muscles (including gastrocnemius) go through a significant loss of mass following unloading. Here we found that in fast muscles an early down-regulation of pro-fusion proteins, through concomitant AMP-activated protein kinase ...
Research Interests: Physiology, Skeletal muscle biology, Mitochondria, Transcription Factors, Transgenic Mice, and 12 moreBiological Sciences, Spinal Muscular Atrophy, Mice, Mitochondrial Dynamics, Animals, Male, Phosphorylation, Skeletal Muscle, Muscle Atrophy, Acetyl CoA Carboxylase, Mitochondrion, and Medical and Health Sciences
It is generally believed that the maximum shortening velocity ( Vo) of a skeletal muscle fiber type does not vary unless a change in myosin heavy chain (MHC) isoform composition occurs. However, recent findings have shown that Vo of a... more
It is generally believed that the maximum shortening velocity ( Vo) of a skeletal muscle fiber type does not vary unless a change in myosin heavy chain (MHC) isoform composition occurs. However, recent findings have shown that Vo of a given fiber type can change after training, suggesting the hypothesis that the function of myosin can vary without a change in isoform. The present study addressed the latter hypothesis by studying the function of isolated myosin isoforms by the use of the in vitro motility assay (IVMA) technique. Four young (age 23–29 yr, YO) and four elderly men (age 68–82 yr, EL) underwent a 12-wk progressive resistance training program of the knee extensor muscles and to one pre- and one posttraining biopsy of the vastus lateralis muscle. The significant increase in one-repetition maximum posttraining in both YO and EL indicated that training was effective. After training, MHC isoform composition showed a shift from MHC2X toward MHC2A in YO and no shift in EL. The ...
Research Interests: Skeletal muscle biology, Aging, Biological Sciences, Cellular mechanotransduction, Humans, and 13 moreApplied, Male, Resistance Training, Exercise, Applied Physiology, Aged, Adult, Age Factors, Muscle contraction, Protein isoforms, Medical and Health Sciences, physical exertion, and Muscle fibers skeletal
Needle biopsy samples were taken from vastus lateralis muscle (VL) of five male body builders (BB, age 27.4+/-0.93 years; mean+/-s.e.m.), who had being performing hypertrophic heavy resistance exercise (HHRE) for at least 2 years, and... more
Needle biopsy samples were taken from vastus lateralis muscle (VL) of five male body builders (BB, age 27.4+/-0.93 years; mean+/-s.e.m.), who had being performing hypertrophic heavy resistance exercise (HHRE) for at least 2 years, and from five male active, but untrained control subjects (CTRL, age 29.9+/-2.01 years). The following determinations were performed: anatomical cross-sectional area and volume of the quadriceps and VL muscles in vivo by magnetic resonance imaging (MRI); myosin heavy chain isoform (MHC) distribution of the whole biopsy samples by SDS-PAGE; cross-sectional area (CSA), force (Po), specific force (Po/CSA) and maximum shortening velocity (Vo) of a large population (n=524) of single skinned muscle fibres classified on the basis of MHC isoform composition by SDS-PAGE; actin sliding velocity (Vf) on pure myosin isoforms by in vitro motility assays. In BB a preferential hypertrophy of fast and especially type 2X fibres was observed. The very large hypertrophy of V...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Physiology, Chemistry, Skeletal muscle biology, Aging, Medicine, and 15 moreCell separation, Biological Sciences, Humans, Exercise, The, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, Aged, Skeletal Muscle, Atrophy, Adult, Muscle contraction, Cell Size, Isomerism, Medical and Health Sciences, and Muscle fibers skeletal
The kinetic properties of the myofibrillar system of atrial and ventricular myocardia of hyperthyroid rats were analyzed by determining ATPase activity and maximum shortening velocity. Hyperthyroidism was induced by daily subcutaneous... more
The kinetic properties of the myofibrillar system of atrial and ventricular myocardia of hyperthyroid rats were analyzed by determining ATPase activity and maximum shortening velocity. Hyperthyroidism was induced by daily subcutaneous injections of triiodothyronine (0.2 mg/kg body wt) for 2 wk. The treatment induced a marked atrial and ventricular hypertrophy and, in ventricular myocardium, an isomyosin shift toward a homogeneous V1 composition. Skinned trabeculae and purified myofibrils were prepared from atrial and ventricular myocardia. Enzymatic assays on the myofibrils showed that both Ca-stimulated ATPase activity and Ca-Mg-dependent ATPase activity had equal values in atrial and ventricular myocardia. In skinned trabeculae during maximal Ca activations, force-velocity curves were determined by load-clamp maneuvers, and unloaded shortening velocity (Vo) was obtained with the slack-test method. Both maximum shortening velocities extrapolated from the force-velocity curves (Vmax...
Research Interests:
The response to caffeine was studied in mouse muscles [diaphragm, soleus, and extensor digitorum longus (EDL)] with different ryanodine receptor isoform (RyR1, RyR3) composition and in single permeabilized muscle fibers dissected from... more
The response to caffeine was studied in mouse muscles [diaphragm, soleus, and extensor digitorum longus (EDL)] with different ryanodine receptor isoform (RyR1, RyR3) composition and in single permeabilized muscle fibers dissected from diaphragm of wild-type (WT) and RyR3-deficient (RyR3−/−) mice at 1, 15, 30, and 60 postnatal days (PND). The caffeine response decreased during development, and, in adult mice, was greater in diaphragm, lower in EDL, and intermediate in soleus. This suggests a direct relation between response to caffeine and RyR3 expression. The lack of RyR3 reduced caffeine response in young, but not in adult mice, and did not abolish the age-dependent variation and the intermuscle differences. In diaphragm single fibers, the response to caffeine increased during development and was reduced in fibers lacking RyR3 both at 15 and 60 PND. A population of fibers highly responsive to caffeine was present in adult WT and disappeared in RyR3−/−. The results confirm the contr...
Research Interests:
Harridge, S. D. R., R. Bottinelli, M. Canepari, M. Pellegrino, C. Reggiani, M. Esbjörnsson, P. D. Balsom, and B. Saltin. Sprint training, in vitro and in vivo muscle function, and myosin heavy chain expression. J. Appl. Physiol. 84(2):... more
Harridge, S. D. R., R. Bottinelli, M. Canepari, M. Pellegrino, C. Reggiani, M. Esbjörnsson, P. D. Balsom, and B. Saltin. Sprint training, in vitro and in vivo muscle function, and myosin heavy chain expression. J. Appl. Physiol. 84(2): 442–449, 1998.—Sprint training represents the condition in which increases in muscle shortening speed, as well as in strength, might play a significant role in improving power generation. This study therefore aimed to determine the effects of sprint training on 1) the coupling between myosin heavy chain (MHC) isoform expression and function in single fibers, 2) the distribution of MHC isoforms across a whole muscle, and 3) in vivo muscle function. Seven young male subjects completed 6 wk of training (3-s sprints) on a cycle ergometer. Training was without effect on maximum shortening velocity in single fibers or in the relative distribution of MHC isoforms in either the soleus or the vastus lateralis muscles. Electrically evoked and voluntary isometri...
Research Interests:
Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with... more
Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observ...
Research Interests: Stem Cells, Skeletal muscle biology, Biology, Adolescent, Medicine, and 15 moreStem Cell Transplantation, Biological Sciences, Humans, Child, Feasibility Studies, Cell, Male, Peptides, Cell Transplantation, Glycoproteins, Duchenne Muscular Dystrophy, Muscle contraction, Immunophenotyping, Medical and Health Sciences, and Immunomagnetic separation
Stretch of active whole muscle causes a sudden yielding of the sarcomeres when the actin and myosin filaments are displaced by 10-12 nm from their isometric position. This behaviour is not normally seen during stretch of singly-dissected... more
Stretch of active whole muscle causes a sudden yielding of the sarcomeres when the actin and myosin filaments are displaced by 10-12 nm from their isometric position. This behaviour is not normally seen during stretch of singly-dissected fibres, but it can be induced by introducing series compliance into the system.
Research Interests:
Research Interests:
Genetically corrected mesoangioblasts from human iPSCs derived from limb-girdle muscular dystrophy patients produce muscle fibers expressing the therapeutic gene in a mouse model of the disease.
Research Interests:
This study was designed to investigate the changes in cardiac contractile properties induced by triiodothyronine (T3) administration in adult rats. Myofibrils and myosin were isolated from ventricular muscles from euthyroid and... more
This study was designed to investigate the changes in cardiac contractile properties induced by triiodothyronine (T3) administration in adult rats. Myofibrils and myosin were isolated from ventricular muscles from euthyroid and hyperthyroid animals and enzymatically and electrophoretically characterized. The time course of the isometric response, the force velocity curve, the force interval relation were studied in papillary muscles isolated from the right ventricles of euthyroid and hyperthyroid rats. T3 administration induced significant increases in Mg2+ activated myofibrillar ATPase activity (+11.4%) and in Ca2+ activated myosin ATPase activity (+20.1%). Significant increases in shortening velocity at low and zero loads (+20.4%) were found in papillary muscles from treated animals when compared with the control muscles. These variations in enzymatic activity and shortening velocity could be related to the increase in the amount of the fast isomyosin V1, as shown by pyrophosphate gel electrophoresis. The negative force-frequency relation at steady state, typical of rat cardiac preparations, was observed in treated and control animals; its slope was, however, halved in hyperthyroid papillary muscles when compared with control ones. In accordance with this finding, the potentiating effect of a prolonged diastolic interval was significantly reduced in hyperthyroid papillary muscles. In the frame of an interpretation of the force interval relation on the basis of the excitation contraction coupling processes, these latter observations might indicate an enhanced activity of the sarcoplasmic reticulum. We conclude that thyroid hormone administration has a dual effect on cardiac contractility, on one hand regulating the synthesis of the different isomyosin and, on the other hand, stimulating the activity of the sarcoplasmic reticulum.
Research Interests:
Research Interests:
Contractile and energetic properties of human skeletal muscle have been studied for many years in vivo in the body. It has been, however, difficult to identify the specific role of muscle fibres in modulating muscle performance. Recently... more
Contractile and energetic properties of human skeletal muscle have been studied for many years in vivo in the body. It has been, however, difficult to identify the specific role of muscle fibres in modulating muscle performance. Recently it has become possible to dissect short segments of single human muscle fibres from biopsy samples and make them work in nearly physiologic
Research Interests: Electrophysiology, Molecular Biology, Skeletal muscle biology, Biology, Calcium, and 12 moreMedicine, Ion Channels, Protein Structure and Function, Humans, Temperature, Molecular Diversity, Functional diversity, Skeletal Muscle, Protein isoforms, Biochemistry and cell biology, Sarcoplasmic reticulum, and Muscle fibers skeletal
Myosin heavy chain composition of a large number (288) of single fibres from slow (soleus), and fast (superficial part of tibialis anterior, and plantaris) muscles of adult (3-5-month-old) Wistar rats was determined. A combination of... more
Myosin heavy chain composition of a large number (288) of single fibres from slow (soleus), and fast (superficial part of tibialis anterior, and plantaris) muscles of adult (3-5-month-old) Wistar rats was determined. A combination of SDS-PAGE and monoclonal antibodies against myosin heavy chains allowed to identify four myosin heavy chain isoforms (1, 2A, 2X, and 2B) and to detect myosin heavy chain coexistence. Four groups of fibres containing only one myosin heavy chain (1 myosin heavy chain, 2A myosin heavy chain, 2X myosin heavy chain, and 2B myosin heavy chain), and five groups containing more than one myosin heavy chain (1 and 2A myosin heavy chains, 2A and 2X myosin heavy chains, 2X and minor amounts of 2B (2X-2B fibres), 2B and minor amounts of 2X (2B-2X fibres), and 2A, 2X, and 2B myosin heavy chain were identified and their relative percentages were assessed. Coexistence of fast myosin heavy chain isoforms was found to be very frequent (50% of the fibres in plantaris, and 30% in tibialis anterior), whereas coexistence of slow and fast (2A) myosin heavy chain was very rare. Maximum shortening velocity (V0) was determined using the slack-test procedure in a subset of 109 fast fibres from the above population. The values of V0 formed a continuum extending from 2A to 2X to 2X-2B to 2B-2X to 2B fibres. 2A fibres had the lowest value of V0 and 2B fibres the highest. Only the differences between 2A and 2B and 2A and 2B-2X fibres were statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
Research Interests:
A recent study has demonstrated that neuromuscular electrical stimulation (NMES) determines, in vitro, a fast-to-slow shift in the metabolic profile of muscle fibers. The aim of the present study was to evaluate if, in the same subjects,... more
A recent study has demonstrated that neuromuscular electrical stimulation (NMES) determines, in vitro, a fast-to-slow shift in the metabolic profile of muscle fibers. The aim of the present study was to evaluate if, in the same subjects, these changes would translate, in vivo, into an enhanced skeletal muscle oxidative metabolism. Seven young men were tested (cycle ergometer) during incremental exercises up to voluntary exhaustion and moderate and heavy constant-load exercises (CLE). Measurements were carried out before and after an 8-wk training program by isometric bilateral NMES (quadriceps muscles), which induced an ∼25% increase in maximal isometric force. Breath-by-breath pulmonary O2 uptake (V̇o2) and vastus lateralis oxygenation indexes (by near-infrared spectroscopy) were determined. Skeletal muscle fractional O2 extraction was estimated by near-infrared spectroscopy on the basis of changes in concentration of deoxygenated hemoglobin + myoglobin. Values obtained at exhausti...
Research Interests: Skeletal muscle biology, Medicine, Biological Sciences, Humans, Near Infrared Spectroscopy, and 15 moreMale, Exercise, Applied Physiology, Hypertrophy, Myoglobin, Oxygen, Adult, Muscle hypertrophy, Neuromuscular Junction, Exercise Test, Oxygen Consumption, Hemoglobins, Pulmonary Gas Exchange, Medical and Health Sciences, and Electric stimulation
The contractile characteristics of three human muscle groups (triceps surae, quadriceps femoris and triceps brachii) of seven young male subjects were examined. The contractile properties were determined from electrically evoked isometric... more
The contractile characteristics of three human muscle groups (triceps surae, quadriceps femoris and triceps brachii) of seven young male subjects were examined. The contractile properties were determined from electrically evoked isometric responses and compared with fibre type composition determined from needle biopsy samples. Fibre types were identified using myosin heavy chain (MHC) isoforms as molecular markers with gel electrophoresis (SDS-PAGE)
Research Interests: Physiology, Chemistry, Skeletal muscle biology, Medicine, Humans, and 13 moreMale, Exercise, Medical Physiology, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, European, Adult, Molecular Marker, Muscle contraction, Densitometry, Gel electrophoresis, Triceps Brachii, Frequency Response, and Heavy Chain
Research Interests:
Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm... more
Beta-agonists and glucocorticoids are frequently coprescribed for chronic asthma treatment. In this study the effects of 4 week treatment with beta-agonist clenbuterol (CL) and glucocorticoid dexamethasone (DEX) on respiratory (diaphragm and parasternal) and limb (soleus and tibialis) muscles of the mouse were studied. Myosin heavy chain (MHC) distribution, fibres cross sectional area (CSA), glycolytic (phosphofructokinase, PFK; lactate dehydrogenase, LDH) and oxidative enzyme (citrate synthase, CS; cytochrome oxidase, COX) activities were determined. Muscle samples were obtained from four groups of adult C57/B16 mice: (1) Control (2) Mice receiving CL (CL, 1.5 mg kg(-1) day(-1) in drinking water) (3) Mice receiving DEX (DEX, 5.7 mg kg(-1) day(-1) s.c.) (4) Mice receiving both treatments (DEX + CL). As a general rule, CL and DEX showed opposite effects on CSA, MHC distribution, glycolytic and mitochondrial enzyme activities: CL alone stimulated a slow-to-fast transition of MHCs, an increase of PFK and LDH and an increase of muscle weight and fibre CSA; DEX produced an opposite (fast-to-slow transition) change of MHC distribution, a decrease of muscle weight and fibre CSA and in some case an increase of CS. The response varied from muscle to muscle with mixed muscles, as soleus and diaphragm, being more responsive than fast muscles, as tibialis and parasternal. In combined treatments (DEX + CL), the changes induced by DEX or CL alone were generally minimized: in soleus, however, the effects of CL predominated over those of DEX, whereas in diaphragm DEX prevailed over CL. Taken together the results suggest that CL might counteract the unwanted effects on skeletal muscles of chronic treatment with glucocorticoids.
Research Interests:
The aims of the present study were as follows: (1) to examine the adaptational changes to chronic endurance voluntary exercise and (2) to investigate the effects of amino acid supplementation on the adaptational changes induced by... more
The aims of the present study were as follows: (1) to examine the adaptational changes to chronic endurance voluntary exercise and (2) to investigate the effects of amino acid supplementation on the adaptational changes induced by endurance training in hindlimb (gastrocnemius, tibialis, soleus) and respiratory (diaphragm) muscles of mice. Male C57Bl6 mice were divided in four groups: control sedentary, sedentary supplemented with amino acid mixture (BigOne, 1.5 mg g day(-1) in drinking water for 8 weeks), running (free access to running wheels for 8 weeks), and running supplemented with amino acid mixture. Myosin heavy chain (MHC) isoform distribution was determined in all muscles considered. Fiber cross-sectional area (CSA) was measured in the soleus muscle. In all muscles except the tibialis, endurance training was associated with an overall shift towards the expression of slower MHC isoforms. Amino acid supplementation produced a shift towards the expression of faster MHC isoforms in the soleus and diaphragm muscles, and partially antagonized the effects of training. Immunohistochemical analysis of CSA of individual muscle fibers from the soleus muscle suggests that voluntary running produced a decrease in the size of type 1 fibers, and amino acid supplementation during training resulted in an increase in size in both type 1 and type 2A fibers. Collectively, these results suggest that the endurance adaptations induced by voluntary running depend on the muscle type, and that amino acid supplementation is able to modulate both fiber size and MHC isoform composition of skeletal muscles in sedentary and exercised mice.
Research Interests: Chemistry, Plasticity, Skeletal muscle biology, Immunohistochemistry, Medicine, and 14 moreMice, Animals, Male, Drinking Water, Myosin, European, Amino Acids, Skeletal Muscle, Amino Acid Profile, Amino Acid Sequence, Endurance Training, Physical Training, Physical Endurance, and cross sectional area
The impact of ageing on force and velocity of human skeletal muscle fibres has been extensively studied. As discrepancies have been reported, it is still unclear whether or not a deterioration of the capacity of muscle fibres to develop... more
The impact of ageing on force and velocity of human skeletal muscle fibres has been extensively studied. As discrepancies have been reported, it is still unclear whether or not a deterioration of the capacity of muscle fibres to develop force and shortening is involved in determining weakness and decrease in shortening velocity of skeletal muscle of elderly people. We compared myosin heavy chain (MHC) isoform distribution of vastus lateralis muscle, and specific force (Po/CSA) and maximum shortening velocity (Vo) of skeletal muscle fibres among one population of young controls (CTRL) and three populations of elderly (EL) subjects with very variable levels of physical activity: sedentary (EL-SED, n = 3); controls (EL-CTRL, n = 4); endurance trained (EL-END, n = 3). Muscle phenotype was progressively faster in the order EL-END --> CTRL --> EL-CTRL --> EL-SED. Po/CSA and Vo also varied among the different populations of elderly subjects generally showing a decreasing deterioration with increasing activity levels. The results suggest that discrepancies observed so far in age-induced deterioration of contractile properties of muscle fibres could depend on the different activity levels of the populations of elderly subjects enrolled in the studies.
Research Interests:
Research Interests: Kinetics, Biophysical Chemistry, Biological Sciences, Humans, Male, and 15 morePhysical sciences, CHEMICAL SCIENCES, Middle Aged, Adult, Protein isoforms, Polyacrylamide Gel Electrophoresis, Protein Binding, Peak Power, Adenosine Triphosphate, Rate Limiting, Cell membrane permeability, Kinetic Scheme, Rate Constant, In Vitro Techniques, and Muscle fibers skeletal
Research Interests:
Isolated atrial and ventricular preparations from rat heart have been compared. In atrial specimens relaxation is faster than in papillary muscles both in isometric and isotonic conditions. In papillary muscles the tension decay occurs... more
Isolated atrial and ventricular preparations from rat heart have been compared. In atrial specimens relaxation is faster than in papillary muscles both in isometric and isotonic conditions. In papillary muscles the tension decay occurs earlier in isotonic than isometric contractions and a stretch applied at or after the peak of isometric twitches promotes a faster relaxation: this load dependence of relaxation is less pronounced in atrial specimens. The decay of activation, evaluated from the decline of the muscle shortening ability, is faster in atrium than in ventricle. These findings suggest that the sensitivity of relaxation to the loading conditions might be determined by both the activation decay rate and the cross bridge kinetics.
Research Interests:
Research Interests:
Research Interests:
A novel laser-diffractometer system for making dynamic measurements of sarcomere lengths in isolated muscle cells is described. The device uses a combination of optical smoothing and digital electronic processing to monitor the angular... more
A novel laser-diffractometer system for making dynamic measurements of sarcomere lengths in isolated muscle cells is described. The device uses a combination of optical smoothing and digital electronic processing to monitor the angular displacement of a diffracted order along a charge-coupled photodiode array. The optical system comprises a cylindrical lens and diffuser which together generate a smooth intensity profile across
Research Interests:
NF-κB is a major pleiotropic transcription factor modulating immune, inflammatory, cell survival, and proliferative responses, yet the relevance of NF-κB signaling in muscle physiology and disease is less well documented. Here we show... more
NF-κB is a major pleiotropic transcription factor modulating immune, inflammatory, cell survival, and proliferative responses, yet the relevance of NF-κB signaling in muscle physiology and disease is less well documented. Here we show that muscle-restricted NF-κB ...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Since the middle of the 1980s, it was understood that myosin, the motor of contraction, can be expressed in several isoforms. The isoforms of the myosin heavy-chain (MHC) portion of the molecule were found to be mostly responsible for the... more
Since the middle of the 1980s, it was understood that myosin, the motor of contraction, can be expressed in several isoforms. The isoforms of the myosin heavy-chain (MHC) portion of the molecule were found to be mostly responsible for the diversity in the contractile and energetic properties of muscle fibers. In humans, three MHC isoforms are expressed in limb muscles (MHC-1, MHC-2A and MHC-2X) and they generate three pure fiber types (types 1, 2A and 2X) and two hybrid types (types 1-2A and -2AX). Type 1, 2A and 2X fibers widely differ with respect to most of their contractile and energetic properties, and a change in their relative distribution within muscles is known to modulate their functional properties in vivo through a "qualitative" mechanism. On the basis of the MHC regulation of muscle fibers properties, it is expected that a given fiber type develops the same force and shortens at the same speed regardless of the physiologic and pathologic conditions under which the muscle works. Surprisingly, several evidences have been accumulating to show that in aging and disuse, the properties of a muscle fiber type can change with no change in its myosin isoform content. This short review considers the latter phenomenon and the possible underlying mechanisms.
Research Interests:
Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival.... more
Extensive loss of skeletal muscle tissue results in mutilations and severe loss of function. In vitro-generated artificial muscles undergo necrosis when transplanted in vivo before host angiogenesis may provide oxygen for fibre survival. Here, we report a novel strategy based upon the use of mouse or human mesoangioblasts encapsulated inside PEG-fibrinogen hydrogel. Once engineered to express placental-derived growth factor, mesoangioblasts attract host vessels and nerves, contributing to in vivo survival and maturation of newly formed myofibres. When the graft was implanted underneath the skin on the surface of the tibialis anterior, mature and aligned myofibres formed within several weeks as a complete and functional extra muscle. Moreover, replacing the ablated tibialis anterior with PEG-fibrinogen-embedded mesoangioblasts also resulted in an artificial muscle very similar to a normal tibialis anterior. This strategy opens the possibility for patient-specific muscle creation for ...