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At least 343 records · Page 19

Differential regulation of protease activated receptor-1 and tissue plasminogen activator expression by shear stress in vascular smooth muscle cells

Recent studies have demonstrated that vascular smooth muscle cells are responsive to changes in their local hemodynamic environment. The effects of shear stress on the expression of human protease activated receptor-1 (PAR-1) and tissue plasminogen activator (tPA) mRNA and protein were investigated in human aortic smooth muscle cells (HASMCs). Under conditions of low shear stress (5 dyn/cm2), PAR-1 mRNA expression was increased transiently at 2 hours compared with stationary control values, whereas at high shear stress (25 dyn/cm2), mRNA expression was decreased (to 29% of stationary control; P<0.05) at all examined time points (2 to 24 hours). mRNA half-life studies showed that this response was not due to increased mRNA instability. tPA mRNA expression was decreased (to 10% of stationary control; P<0.05) by low shear stress after 12 hours of exposure and was increased (to 250% of stationary control; P<0.05) after 24 hours at high shear stress. The same trends in PAR-1 mRNA levels were observed in rat smooth muscle cells, indicating that the effects of shear stress on human PAR-1 were not species-specific. Flow cytometry and ELISA techniques using rat smooth muscle cells and HASMCs, respectively, provided evidence that shear stress exerted similar effects on cell surface-associated PAR-1 and tPA protein released into the conditioned media. The decrease in PAR-1 mRNA and protein had functional consequences for HASMCs, such as inhibition of [Ca2+] mobilization in response to thrombin stimulation. These data indicate that human PAR-1 and tPA gene expression are regulated differentially by shear stress, in a pattern consistent with their putative roles in several arterial vascular pathologies.

NASA Discipline Cell Biology↗

cAMP levels in fast- and slow-twitch skeletal muscle after an acute bout of aerobic exercise

The present study examined whether exercise duration was associated with elevated and/or sustained elevations of postexercise adenosine 3',5'-cyclic monophosphate (cAMP) by measuring cAMP levels in skeletal muscle for up to 4 h after acute exercise bouts of durations that are known to either produce (60 min) or not produce (10 min) mitochondrial proliferation after chronic training. Treadmill-acclimatized, but untrained, rats were run at 22 m/min for 0 (control), 10, or 60 min and were killed at various postexercise (0, 0.5, 1, 2, and 4 h) time points. Fast-twitch white and red (quadriceps) and slow-twitch (soleus) muscles were quickly excised, frozen in liquid nitrogen, and assayed for cAMP with a commercial kit. Unexpectedly, cAMP contents in all three muscles were similar to control (nonexercise) at most (21 of 30) time points after a single 10- or 60-min run. Values at 9 of 30 time points were significantly different from control (P < 0.05); i.e., 3 time points were significantly higher than control and 6 were significantly less than control. These data suggest that the cAMP concentration of untrained skeletal muscle after a single bout of endurance-type exercise is not, by itself, associated with exercise duration.

NASA Discipline Musculoskeletal↗

Comparison of contraction times of a muscle and its motor units

The twitch contraction time (CT) for each of 13 soleus (SOL) and 13 medial gastrocnemius (MG) muscles was compared with the mean CT from a sample of its motor units (MUs; 356 total) to see if the CT of a whole muscle when tested at its optimal length (Lo) differed systematically from that of its MUs tested at their individual Lo's. The CTs of the whole muscle were significantly longer in the ratio of 1.13. This is consistent with a hypothesis that electrical-field effects result in a more protracted contraction of the individual muscle fiber.

Non-NASA Center↗

Assessment of Individualizing lactobacillus plantarum Supplementation with Precision Health to Preserve Muscle Health in Astronauts During Long Duration Spaceflight

Muscle atrophy is an unfortunate reality seen after spending time in microgravity. Decreases in muscle strength, size, and endurance can negatively impact mission productivity and increase the risk of injury in astronauts. In preparing for long-duration spaceflight aboard future orbiting stations and interplanetary vessels, supplementation with lactobacillus plantarum has been suggested as a possible countermeasure for crew members. Early clinical trials have shown the probiotic to improve muscle strength, endurance, and associated biomarkers, even without significant physical exercise by influencing the gut-muscle-axis. While current onboard exercise protocols have significantly helped limit degradation (as seen below), individualized implementation of this supplement could not only add another layer of protection but also protect against inadequate exercise equipment on future missions due to payload constraints

Precision Health↗

Fiber size and myosin phenotypes of selected rhesus lower limb muscles after a 14-day spaceflight

Muscle biopsies were taken from the rhesus (Macaca mulatta) soleus (Sol, a slow ankle extensor), medial gastrocnemius (MG, a fast ankle extensor), tibialis anterior (TA, a fast ankle flexor), and vastus lateralis (VL, a fast knee extensor) muscles in vivarium controls (n=5) before and after either a 14-day spaceflight (Bion 11, n=2) or a 14-day ground-based flight simulation (n=3). Myosin heavy chain (MHC) composition (gel electrophoresis), fiber type distribution (immunohistochemistry), and fiber size were determined. Although there were no significant changes, each muscle showed trends towards adaptation.

NASA Discipline Musculoskeletal↗

Role of insulin-like growth factor-I in the regulation of skeletal muscle adaptation to increased loading

Adaptations in muscle mass stimulated by changes in muscle loading state entail alternations in the synthesis and degradation of myofiber proteins and the modulation of myonuclear number such that the ratio between the number of myonuclei and the size of the myofibers remains relatively constant. As depicted schematically in Figure 2.6, the literature regarding the role of IGF-in mediating muscle adaptation to alterations in loading state suggests the following conclusions: During periods of increased loading, myofibers upregulate the expression and secretion of IGF-I. Acting as an autocrine and/or paracrine growth factor, IGF-I stimulates myofiber anabolic processes. Acting as a paracrine growth factor, IGF-I also stimulates adjacent satellite cells to enter the cell cycle and proliferate. Continued myofiber production of IGF-I stimulates some satellite cells to differentiate and then fuse with myofibers, thus providing additional myonuclei in order to maintain or reestablish the myonucleus to myofiber size ratios of the enlarged myofibers.

Review, Academic↗

Growth hormone, IGF-I, and exercise effects on non-weight-bearing fast muscles of hypophysectomized rats

The effects of growth hormone (GH) or insulin-like growth factor I (IGF-I) with or without exercise (ladder climbing) in countering the effects of unweighting on fast muscles of hypophysectomized rats during 10 days of hindlimb suspension were determined. Compared with untreated suspended rats, muscle weights were 16-29% larger in GH-treated and 5-15% larger in IGF-I-treated suspended rats. Exercise alone had no effect on muscle weights. Compared with ambulatory control, the medial gastrocnemius weight in suspended, exercised rats was larger after GH treatment and maintained with IGF-I treatment. The combination of GH or IGF-I plus exercise in suspended rats resulted in an increase in size of each predominant fiber type, i.e., types I, I + IIa and IIa + IIx, in the medial gastrocnemius compared with untreated suspended rats. Normal ambulation or exercise during suspension increased the proportion of fibers expressing embryonic myosin heavy chain in hypophysectomized rats. The phenotype of the medial gastrocnemius was minimally affected by GH, IGF-I, and/or exercise. These results show that there is an IGF-I, as well as a GH, and exercise interactive effect in maintaining medial gastrocnemius fiber size in suspended hypophysectomized rats.

NASA Center ARC↗

Hypodynamic and hypokinetic condition of skeletal muscles

Data are presented in regard to the effect of unilateral brachial amputation on the physiological characteristics of two functionally different muscles, the brachial muscle (flexor of the brachium) and the medial head of the brachial triceps muscle (extensor of the brachium), which in rats represents a separate muscle. Hypokinesia and hypodynamia were studied.

Katinas, G. S.↗

Protein synthesis rates in atrophied gastrocnemius muscles after limb immobilization

Noting that protein synthesis declines in the gastrocnemius 6 hr after immobilization, the study sought to detect an increase of protein synthesis when the limb was freed, and to examine the effects of exercise on the rate of increase. Rats were used as subjects, with their hind legs in plaster of Paris in plantar flexion to eliminate strain on the gastrocnemius. Periods of immobilization were varied and samples of blood from the muscle were taken to track protein synthesis rates for different groups in immobilization and exercise regimens (running and weightlifting). Synthesis rates declined 3.6% during time in the cast, then increased 6.3%/day after the casts were removed. Both running and weightlifting were found to increase the fractional rate of protein formation in the gastrocnemius muscle when compared with contralateral muscles that were not exercised and were used as controls, suggesting that the mechanism controlling protein synthesis in skeletal muscles is rapidly responsive to changes in muscular contractile activity.

Tucker, K. R.↗

Enhanced skeletal muscle insulin sensitivity in year-old rats adapted to hypergravity

Rats induced into a hypermetabolic state by exposure to chronic (7 mo) centrifugation at 4.15 g exhibited increased glucose uptake at lower plasma insulin levels than weight-matched control animals following oral glucose administration. In order to determine the insulin sensitivity of specific tissues, the effect of exogenous insulin on glucose uptake by isolated perfused livers and hindlim skeletal muscle from rats adapted to chronic centrifugation for one year was compared with perfused tissue from 2.5 mo-old noncentrifuged control animals of equal body weight. Metabolic glucose clearance by skeletal muscle from hypergravic rats did not prove significantly greater than control muscle when perfused in the absence of insulin (10.6 vs 8.1 microliters/min-g-muscle), but was twice as fast (23.0 vs 9.5) at perfusate insulin levels of 35 micro-U/ml. Conversely, glucose uptake by hypergravic livers was significantly decreased (P is less than 0.001) compared with control livers (10.3 vs 27.8) at perfusate insulin levels of 40 micro-U/ml. Results suggest that skeletal muscle rather than liver is primarily responsible for the enhanced sensitivity to insulin and the increased energy expenditure observed in rats subjected to hypergravity.

Mondon, C. E.↗

Morphometric analysis of rat muscle fibers following space flight and hypogravity

The effect of hypogravity on striate muscles, containing both fast twitch glycolytic and slow twitch oxidative fibers, was studied in rats aboard two Cosmos biosatellites. Results of a computer-assisted image analysis of extensor digitorum muscles from five rats, exposed to 18.5 days of hypogravity and processed for the alkaline ATPase reaction, showed a reduction of the mean fiber diameter (41.32 + or - 0.55 microns), compared to synchronous (46.32 + or - 0.55 microns) and vivarium (49 + or - 0.5 microns) controls. A further experiment studied the ratio of fast to slow twitch fibers in 25 rats exposed to 18.5 days of hypogravity and analyzed at four different periods of recovery following the space flight. Using the previous techniques, the gastrocnemius muscle showed a reduction of the total muscle fiber area in square microns and a reduction in the percentage of slow fibers of flight animals compared to the control animals.

Chui, L. A.↗

Atrophy of rat skeletal muscles in simulated weightlessness

A hypokinetic rat model was used for elucidation of the mechanism of skeletal muscle wasting which occurs in weightlessness. Rats were suspended from a back-harness with the head tilted downward and the hind limbs totally unloaded. A progressive decrease in the size of the soleus muscle from suspended rats was observed as a function of time. The rate of protein degradation of the homogenates from the soleus muscles of suspended and control animals was not significantly different. The rate of cell-free protein synthesis was severely repressed in the atrophied muscle. An initial rise in the levels of plasma glucose and corticosterone was observed on the second day of suspension, but they subsequently returned to normal values.

Feller, D. D.↗

Effect of hindlimb immobilization on the fatigability of skeletal muscle

The effect of 6 weeks of disuse atrophy produced by hindlimb immobilization was studied in situ (33.5 C) in the soleus and extensor digitorum longus muscles of rats. The results indicate that disuse causes preferential alterations in the isometric contractile properties of slow-twitch, as opposed to fast-twitch, skeletal muscles. During continuous contractile activity, atrophied muscles were found to have lower ATP levels and an apparent increase in their dependence on anaerobic metabolism, as reflected by the more extensive depletion of glycogen and enhanced lactate formation. Although the atrophied muscles were determined to have fewer cross bridges and thus generated lower tension, the pattern of decline in active cross-bridge formation and tetanic tension during contractile activity was found to proceed in a manner similar to controls.

Witzmann, F. A.↗

Androgens enhance in vivo 2-deoxyglucose uptake by rat striated muscle

It is shown that testosterone propionate (TP) causes a striking increase in the in vivo uptake of 2-deoxyglucose (2-DG) by the levator ani muscle of immature male rats, which was found to be uniformly distributed over the entire muscle. After a single subcutaneous injection of TP, no enhancement of 2-DG was observed before 3.5 hr, at which time uptake was increased 2-fold; maximum enhancement (4-fold) was attained at 12 hr. At 72 hr, 2-DG uptake remained elevated at twice the control value. It was determined that the effect of TP probably is mediated by specific androgen receptors. In addition, it was found that the effect of TP was blocked by the simultaneous administration of an androgen antagonist, cyproterone acetate. TP also was found to enhance the uptake of 2-DG in the bulbocavernosus (253 percent over control) and extensor digitorum longus muscles (150 percent over control), but not in the biceps brachii or soleus. It is suggested that the increased uptake of glucose may be an important early step in the anabolic response of muscle to androgens.

Max, S. R.↗

Physiological changes in fast and slow muscle with simulated weightlessness

A rat hindlimb suspension model of simulated weightlessness was used to examine the physiological characteristics of skeletal muscle. The physiological sequelae of hindlimb suspension were compared to those of spinal cord section, denervation by sciatic nerve crush, and control. Muscle examined were the predominantly slow (Type 1) soleus (SOL) and the predominantly fast (Type 2) extensor digitorum longus (EDL). Two procedures which alter motor unit activity, hindlimb suspension and spinal cord section, produce changes in characteristics of skeletal muscles that are dependent upon fiber type. The SOL develops characteristics more representative of a fast muscle, including smaller Type 1 fiber proportion and higher AChE activity. The EDL, which is already predominantly fast, loses most of its few Type 1 fibers, thus also becoming faster. These data are in agreement with the studies in which rats experienced actual weightlessness.

Dettbarn, W. D.↗

Research opportunities in muscle atrophy

Muscle atrophy in a weightless environment is studied. Topics of investigation include physiological factors of muscle atrophy in space flight, biochemistry, countermeasures, modelling of atrophied muscle tissue, and various methods of measurement of muscle strength and endurance. A review of the current literature and suggestions for future research are included.

Herbison, G. J.↗

Contractile properties of rat fast-twitch skeletal muscle during reinnervation - Effects of testosterone and castration

The peroneal nerve of subject rats were crushed 1 cm from the muscle in order to examine the isometric contractile properties of skeletal muscle in the recovery sequency during reinnervation of normal, castrated, and testosterone-treated rats. The particular muscle studied was the extensor digitorum longus, with functional reinnervation first observed 8-9 days after nerve crush. No evidence was found that either castration or testosterone injections altered the process of reinnervation after the nerve crush, with the conclusion being valid at the 0.05 p level. The most reliable index of reinnervation was found to be the twitch:tetanus ratio, a factor of use in future studies of the reinnervation of skeletal muscle.

Yeagle, S. P.↗

Glucocorticoid sensitivity, disuse, and the regulation of muscle mass

A new noninvasive immobilization procedure to be used on rats has been developed to study immobilization-induced muscle hypersensitivity to normal glucocorticoid concentration, subsequent muscle atrophy, and atrophy recovery. The immobilization procedure involves encasing the hind limb in a light-weight plasticlike cast (10 percent the usual plaster weight), completely resistant to animal gnawing. The effects of right-angle immobilization of the ankle on the slow fiber soleus, and the fast fiber extensor digitorum longus, resemble the effects of weightlessness. The increased concentration of glucocorticoid receptor sites in immobilized and denervated muscle is discussed, along with the chronic loss of muscle mass that occurs in practically all dystrophies. It is concluded that lack of mechanical work in a zero gravity environment is a major cause of glucocorticoid hypersensitivity in the body's musculature.

Almon, R. R.↗