Min Liu

A quantitative study of bioenergetics in skeletal muscle lacking carbonic anhydrase III using 31P magnetic resonance spectroscopy

Oxidative slow skeletal muscle contains carbonic anhydrase III in high concentration, but its primary function remains unknown. To determine whether its lack handicaps energy metabolism and/or acid elimination, we measured the intracellular pH and energy phosphates by 31P magnetic resonance spectroscopy in hind limb muscles of wild-type and CA III knockout mice during and after ischemia and intense exercise (electrical stimulation). Thirty minutes of ischemia caused phosphocreatine (PCr) to fall and Pi to rise while pH and ATP remained constant in both strains of mice. PCr and Pi kinetics during ischemia and recovery were not significantly different between the two genotypes. From this we conclude that under neutral pH conditions resting muscle anaerobic metabolism, the rate of the creatine kinase reaction, intracellular buffering of protons, and phosphorylation of creatine by mitochondrial oxygen metabolism are not influenced by the lack of CA III. Two minutes of intense stimulation of the mouse gastrocnemius caused PCr, ATP, and pH to fall and ADP and Pi to rise, and these changes, with the exception of ATP, were all significantly larger in the CA III knockouts. The rate of return of pH and ADP to control values was the same in wild-type and mutant mice, but in the mutants PCr and Pi recovery were delayed in the first minute after stimulation. Because the tension decrease during fatigue is known to be the same in the two genotypes, we conclude that a lack of CA III impairs mitochondrial ATP synthesis.

Overexpression of insulin-like growth factor-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse

•  What is the central question of this study? Insulin‐like growth factor‐1 (IGF‐1) promotes muscle hypertrophy, but no studies have investigated the effect of IGF‐1 on the susceptibility of atrophied muscles to reloading‐induced muscle injury. •  What is the main finding and what is its importance? We employed a comprehensive set of methods, including muscle physiological measurements, molecular biology techniques and non‐invasive magnetic resonance imaging. The results concurrently demonstrate that local overexpression of IGF‐1 in a primary antigravity muscle protects the muscle from reloading‐induced muscle damage and accelerates muscle regeneration and functional recovery following cast immobilization. These findings add new physiological significance to the benefits of IGF‐1 on skeletal muscle mass and force generation during varied loading conditions.

Impact of viral mediated IGF-I gene transfer on skeletal muscle following cast immobilization

Insulin-like growth factor I (IGF-I) is a potent myogenic factor that plays a critical role in muscle regeneration and muscle hypertrophy. The purpose of this study was to evaluate the effect of IGF-I overexpression on the recovery of muscle size and function during reloading/reambulation after a period of cast immobilization in predominantly fast twitch muscles. In addition, we investigated concomitant molecular responses in IGF-I receptor and binding proteins (BPs). Recombinant adeno-associated virus vector for IGF-I (rAAV-IGF-IA) was injected into the anterior compartment of one of the hindlimbs of young (3 wk) C57BL6 female mice. At 20 wk of age, both hindlimbs were cast immobilized in a shortened position for 2 wk to unload the tibialis anterior (TA) and extensor longus digitorum (EDL) muscles. The TA and EDL muscles were removed bilaterally after 2 wk of cast immobilization and after 1 and 3 wk of free cage reambulation. Increases in IGF-I mRNA and protein levels with IGF-I overexpression were associated with significant increases in muscle wet weight, fiber size, and tetanic force, although overexpression did not protect against cast immobilization-induced muscle atrophy. After 1 wk of reambulation, evidence of enhanced muscle regeneration was noted in IGF-I-overexpressing muscles with an increased prevalence of central nuclei, embryonic myosin, and Pax7 positive fibers. We also observed larger relative gains in muscle size (wet weight and fiber area), but not force, during the 3-wk reambulation period in hindlimb muscles overexpressing IGF-I compared with contralateral control legs. Changes in IGFBP-5 mRNA expression during cast immobilization and reambulation paralleled those of IGF-I, whereas IGFBP-3 expression changed inversely to IGFBP-5.

A longitudinal study of skeletal muscle following spinal cord injury and locomotor training

Study design:Experimental rat model of spinal cord contusion injury (contusion SCI).Objective:The objectives of this study were (1) to characterize the longitudinal changes in rat lower hindlimb muscle morphology following contusion SCI by using magnetic resonance imaging and (2) to determine the therapeutic potential of two types of locomotor training, treadmill and cycling.Setting:University research setting.Methods:After moderate midthoracic contusion SCI, Sprague–Dawley rats were assigned to either treadmill training, cycle training or an untrained group. Lower hindlimb muscle size was examined prior to SCI and at 1-, 2-, 4-, 8-, and 12-week post injury.Results:Following contusion SCI, we observed significant atrophy in all rat hindlimb muscles with the posterior muscles (triceps surae and flexor digitorum) showing greater atrophy than the anterior muscles (tibialis anterior and extensor digitorum). The greatest amount of atrophy was measured at 2-week post injury (range from 11 to 26%), and spontaneous recovery in muscle size was observed by 4 weeks post-SCI. Both cycling and treadmill training halted the atrophic process and accelerated the rate of recovery. The therapeutic influence of both training interventions was observed within 1 week of training and no significant difference was noted between the two interventions, except in the tibialis anterior muscle. Finally, a positive correlation was found between locomotor functional scores and hindlimb muscle size following SCI.Conclusions:Both treadmill and cycle training diminish the extent of atrophy and facilitate muscle plasticity after contusion SCI.

Overexpression of IGF-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse

•  What is the central question of this study? Insulin‐like growth factor‐1 (IGF‐1) promotes muscle hypertrophy, but no studies have investigated the effect of IGF‐1 on the susceptibility of atrophied muscles to reloading‐induced muscle injury. •  What is the main finding and what is its importance? We employed a comprehensive set of methods, including muscle physiological measurements, molecular biology techniques and non‐invasive magnetic resonance imaging. The results concurrently demonstrate that local overexpression of IGF‐1 in a primary antigravity muscle protects the muscle from reloading‐induced muscle damage and accelerates muscle regeneration and functional recovery following cast immobilization. These findings add new physiological significance to the benefits of IGF‐1 on skeletal muscle mass and force generation during varied loading conditions.

Transcriptional Pathways Associated with Skeletal Muscle Changes after Spinal Cord Injury and Treadmill Locomotor Training

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and corrected with treadmill training. The BMP pathway was differentially activated with early treadmill training as shown by Ingenuity Pathway Analysis. The expression of several muscle mass regulators was modulated by treadmill training, including Fst, Jun, Bmpr2, Actr2b, and Smad3. In addition, key players in fatty acids metabolism (Lpl and Fabp3) responded to both SCI induced inactivity and reloading with training. The decrease in Smad3 and Fst early after the initiation of treadmill training was confirmed by RT-PCR. Our data suggest that TGFβ/Smad3 signaling may be mainly involved in the decrease in muscle mass observed with SCI, while the BMP pathway was activated with treadmill training.

Comparison of Soil P Test Procedures for St. Augustinegrass

St. Augustinegrass [Stenotaphrum secondatum (Walt.) Kuntze] is a home lawn grass widely used in the southern United States. At present, phosphorus (P) fertilization of St. Augustinegrass is based primarily on Mehlich 1 P test. One criticism of Mehlich 1 extractant is that it extracts some fraction of soil P pool that is not available to plants, whereas, iron (Fe) oxide P and water‐extractable P methods are reported to be better related to plant growth in some cases. Literature relative to the soil test procedure comparison for St. Augustinegrass was not found. The objective of this study was to evaluate Mehlich 1 P, Fe oxide P, and water‐extractable P to identify the most suitable soil test method for St. Augustinegrass growth. Established pots of ‘Floratam’ were subjected to P application of 0, 0.14, 0.27, 0.54, and 1.07 g m−2 every 4 wk for 12 wk. Measurements included tissue growth rates, tissue P concentration, soil Mehlich 1 P, Fe oxide P, and water‐extractable P concentrations. Phosphorus application increased soil test P concentrations. Soil Mehlich 1 P, Fe oxide P, and water‐extractable P concentrations were closely correlated to each other. Three soil test P levels and tissue P concentrations were highly correlated with Mehlich 1 P, which best predicted tissue P levels. Three soil test P levels were also closely correlated to the St. Augustinegrass top growth rate. Critical minimum Fe oxide P and water‐extractable P concentration was 3 mg kg−1. Overall, Mehlich 1 P was the best soil P test for St. Augustinegrass among the three extractants tested.

Overexpression of insulin-like growth factor-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse: Insulin-like growth factor-1 and reloading-induced muscle damage after disuse

•  What is the central question of this study? Insulin‐like growth factor‐1 (IGF‐1) promotes muscle hypertrophy, but no studies have investigated the effect of IGF‐1 on the susceptibility of atrophied muscles to reloading‐induced muscle injury. •  What is the main finding and what is its importance? We employed a comprehensive set of methods, including muscle physiological measurements, molecular biology techniques and non‐invasive magnetic resonance imaging. The results concurrently demonstrate that local overexpression of IGF‐1 in a primary antigravity muscle protects the muscle from reloading‐induced muscle damage and accelerates muscle regeneration and functional recovery following cast immobilization. These findings add new physiological significance to the benefits of IGF‐1 on skeletal muscle mass and force generation during varied loading conditions.