Biomedical subjects

Fuminori Kawano

Publications and source records attributed to Fuminori Kawano.

At least 19 recordsLinked to original sources

PubMed2006

Leucine-induced activation of translational initiation is partly regulated by the branched-chain alpha-keto acid dehydrogenase complex in C2C12 cells.

Branched-chain amino acid leucine has been shown to activate the translational regulators through the mammalian target of rapamycin. However, the leucine's effects are self-limiting because leucine promotes its own disposal by an oxidative pathway. The irreversible and rate-limiting step in the leucine oxidation pathway is catalyzed by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex. The complex contains E1 (alpha2beta2), E2, and E3 subunits, and its activity is abolished by phosphorylation of the E1alpha subunit by BCKDH kinase. The relationship between the activity of BCKDH complex and leucine-mediated activation of the protein translation was investigated using the technique of RNA interference. The activity of BCKDH complex in C2C12 cell was modulated by transfection of small interfering RNA (siRNA) for BCKDH E2 subunit or BCKDH kinase. Transfection of siRNAs decreased the mRNA expression and protein amount of corresponding gene. Suppression of either E2 subunit or kinase produced opposite effects on the cell proliferation and the activation of translational regulators by leucine. Suppression of BCKDH kinase for 48h resulted in decreasing cell proliferation. In contrast, E2 suppression led to increased amount of total cellular protein. The phosphorylation of p70 S6 kinase by leucine was increased in E2-siRNA transfected C2C12 cells, whereas the leucine's effect was diminished in kinase-siRNA transfected cells. These results suggest that the activation of the translational regulators by leucine was partly regulated by the activity of BCKDH complex.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed2006

The role of neural and mechanical influences in maintaining normal fast and slow muscle properties.

The relative importance of neural and mechanical influences in maintaining normal slow and fast muscle properties remains unclear. To address this issue, we studied the effects of 10 days of hindlimb unloading (HU) with or without tenotomy and/or denervation on the cross-sectional area (CSA), myosin heavy chain (MHC) expression (immunohistochemistry) and composition (gel electrophoresis), and myonuclear number in soleus and plantaris fibers in adult male Wistar rats. In general, the adaptations in fiber type and size were similar using either single fiber gel or immunohistochemical analyses. HU resulted in atrophy of type I and I+IIa/x MHC fibers in the soleus and in type I, I+IIa/x, IIa/x, IIa/x+IIb, and IIb MHC fibers in the plantaris. Addition of tenotomy and/or denervation in HU rats had minimal effects on fiber CSA in the soleus, but fiber CSA in the plantaris further decreased, particularly in fibers expressing only fast MHCs. HU resulted in a de novo appearance of type I+IIa/x+IIb and IIa/x+IIb MHC fibers in the soleus and of type I+IIa/x+IIb MHC fibers in the plantaris. Tenotomy and/or denervation in HU rats had no further effect on the fiber type composition of either muscle. Mean myonuclear number/mm of type I fibers was decreased in the soleus of HU rats, and increased in type I and I+IIa/x fibers in HU plus tenotomy (HU+Ten) rats. In the plantaris, mean myonuclear number/mm of type IIa/x, IIa/x+IIb, and IIb fibers was lower after HU with or without tenotomy and/or denervation. Mean cytoplasmic volume/myonucleus ratio of type I and I+IIa/x fibers in the soleus of the HU group tended to be smaller than in controls. The largest decrease was noted in the HU+Ten group. In the plantaris, this ratio was unaffected by HU alone, but was decreased by addition of tenotomy and/or denervation when all fiber types were combined. These data indicate that the major cause of fiber atrophy and adaptations in myonuclear domain size in the slow soleus of HU rats is the chronic reduction in force generation, whereas the elimination of neuromuscular contact via denervation results in additional fiber atrophy and adaptations in myonuclear domain size in the fast plantaris.

Animals↗

PubMed2005

Hyperbaric exposure with high oxygen concentration enhances oxidative capacity of neuromuscular units.

The effects of hyperbaric exposure with high oxygen concentration on spinal motoneurons and the skeletal muscle fibers that they innervate were investigated. Five-week-old male rats were exposed to a hyperbaric (1.25 atmospheric pressure) environment with a high oxygen concentration (35.0%) for 6h daily. The number, cell body size, and oxidative enzyme activity of motoneurons innervating the soleus and plantaris muscles were examined after 8 weeks of hyperbaric exposure. In addition, the fiber type distribution, cell size, and oxidative enzyme activity of the slow soleus and fast plantaris muscles were examined. The oxidative enzyme activity of alpha motoneurons innervating the soleus and plantaris muscles increased after hyperbaric exposure, irrespective of their cell body sizes. The percentage of high-oxidative fibers in the soleus and plantaris muscles increased after hyperbaric exposure. The oxidative enzyme activity of all types of fibers in the soleus and plantaris muscles increased after hyperbaric exposure. It is concluded that hyperbaric exposure with high oxygen concentration enhances the oxidative capacity of neuromuscular units.

Adenosine Triphosphatases↗

PubMed2004

Effects of running exercise during recovery from hindlimb unloading on soleus muscle fibers and their spinal motoneurons in rats.

The effects of hindlimb unloading and recovery with or without running exercise on morphological and metabolic properties of soleus muscle fibers and their spinal motoneurons in rats were investigated. Ten-week-old rats were hindlimb suspended for 2 weeks and thereafter were rehabilitated with or without voluntary running exercise for 2 weeks. A decreased percentage of type I fibers and atrophy of all types of fibers were observed after hindlimb unloading. In addition, decreased oxidative enzyme activity of all types of fibers was observed after hindlimb unloading. In contrast, an improvement in the decreased percentage of type I fibers, decreased fiber cross-sectional area, and decreased fiber oxidative enzyme activity was observed after recovery with running exercise, but not without running exercise. There were no changes in the number, cell body size, or oxidative enzyme activity of motoneurons innervating the soleus muscle after hindlimb unloading or recovery with or without running exercise. These results indicate that running exercise is beneficial for the recovery of the decreased percentage of type I fibers and the atrophy and decreased oxidative enzyme activity of all types of fibers in the soleus muscle induced by hindlimb unloading and that there are no changes in morphological or metabolic properties of spinal motoneurons innervating the soleus muscle following decreased or increased neuromuscular activity.

Animals↗

PubMed2004

The mechanisms underlying neuromuscular changes in microgravity environment.

We reported that the levels of electromyogram in soleus muscle and the afferent neurogram recorded at L5 segmental level of the spinal cord were instantly decreased in response to exposure to microgravity (micro-G) environment created during a parabolic flight, although these activities were constantly presented at 1-G. It was also observed that the soleus muscle length was passively shortened in micro-G due to the plantarflexion of ankle joint. Similar phenomena were also induced by acute hindlimb suspension at 1-G. Further, the soleus muscle atrophied, if the dorsal root at L5 was transected. These results suggested that the unloading-related effects on muscle are closely associated with the inhibition of the afferent input. However, effects of gravity on most of the cells in the whole body can not be removed, although hindlimb suspension can inhibit the antigravity activity of rat hindlimb muscles. And parabolic flight can create micro-G only for a short period of time. Further, effects of hypergravity before and after micro-G are unavoidable. Therefore, further experiments utilizing space environment are essential.

Animals↗

PubMed2004

Role of gravity in mammalian development: effects of hypergravity and/or microgravity on the development of skeletal muscles.

Effects of hindlimb suspension or exposure to 2-G between postnatal day 4 and month 3 and of 3-month recovery at 1-G environment on the characteristics of rat hindlimb muscles were studied. Pronounced growth inhibition was induced by unloading, but not by 2-G loading. It is suggested that the development and/or differentiation of soleus muscle fibers are closely associated with gravitational loading. The data indicated that gravitational unloading during postnatal development inhibits the myonuclear accretion in accordance with subnormal numbers of both mitotic active and quiescent satellite cells. Even though the fiber formation and longitudinal fiber growth were not influenced, cross-sectional growth of muscle fibers was also inhibited in association with lesser myonuclear domain and DNA content per unit volume of myonucleus. Unloading-related inhibition was generally normalized following the recovery.

Animals↗

PubMed2004

Responses of neuromuscular systems under gravity or microgravity environment.

Hindlimb suspension of rats induces induces fiber atrophy and type shift of muscle fibers. In contrast, there is no change in the cell size or oxidative enzyme activity of spinal motoneurons innervating muscle fibers. Growth-related increases in the cell size of muscle fibers and their spinal motoneurons are inhibited by hindlimb suspension. Exposure to microgravity induces atrophy of fibers (especially slow-twitch fibers) and shift of fibers from slow- to fast-twitch type in skeletal muscles (especially slow, anti-gravity muscles). In addition, a decrease in the oxidative enzyme activity of spinal motoneurons innervating slow-twitch fibers and of sensory neurons in the dorsal root ganglion is observed following exposure to microgravity. It is concluded that neuromuscular activities are important for maintaining metabolism and function of neuromuscular systems at an early postnatal development and that gravity effects both efferent and afferent neural pathways.

Afferent Pathways↗

PubMed2004

Load-dependent regulation of neuromuscular system.

Roles of gravitational loading, sarcomere length, and/or tension development on the electromyogram (EMG) of soleus and afferent neurogram recorded at the L5 segmental level of spinal cord were investigated during parabolic flight of a jet airplane or hindlimb suspension in conscious rats. Both EMG and neurogram levels were increased when the gravity levels were elevated from 1-G to 2-G during the parabolic flight. They were decreased when the hindlimbs were unloaded by exposure to actual microgravity or by suspension. These phenomena were related to passive shortening of muscle fibers and/or sarcomeres. Unloading-related decrease in sarcomere length was greater at the central rather than the proximal and distal regions of fibers. These activities and tension development were not detected when the mean sarcomere length was less than 2.03 micrometers. It is suggested that load-dependent regulation of neuromuscular system is related to the tension development which is influenced by sarcomere length.

Animals↗

PubMed2003

Growth-related changes in cell body size and succinate dehydrogenase activity of spinal motoneurons innervating the rat soleus muscle.

Cell body sizes and oxidative enzyme (succinate dehydrogenase) activities of spinal motoneurons innervating the soleus muscle were determined in rats ranging in postnatal age from 3 to 13 weeks. The soleus motoneurons were labeled by a retrograde neuronal tracer, nuclear yellow. The mean cell body sizes of motoneurons increased from 3 to 7 weeks of age, while the mean succinate dehydrogenase activities of motoneurons decreased from 3 to 7 weeks of age. There were no changes in mean cell body size or mean succinate dehydrogenase activity of motoneurons from 7 to 13 weeks of age. An inverse relationship between cell body size and succinate dehydrogenase activity of motoneurons was observed, irrespective of age. These results indicate that motoneurons innervating the rat soleus muscle show the adult pattern of cell body size and succinate dehydrogenase activity at an earlier stage of postnatal growth, 7 weeks of age.

Aging↗

PubMed2003

Upregulation of HSP72 in reloading rat soleus muscle after prolonged hindlimb unloading.

To clarify the changes of heat shock protein (HSP) 72 in the rat soleus muscle after hind-limb unloading (HU) and during reloading, 7-week-old male Wistar rats were hind-limb-suspended for 9 weeks, thereafter ambulatory recovery was permitted for 8 weeks. The body and absolute soleus weights were significantly lower in the HU than in the age-matched control group after HU and during reloading. The soleus weight relative to body weight was also significantly lower in the HU than in the age-matched control group at the end of 9 weeks of suspension, but returned to the control level after 2 weeks of reloading. The HSP72 content decreased to 38% of the control level after HU and conversely increased to 165 and 175% of the control level after 2 and 4 weeks of reloading, respectively. The HSP72 content returned to the control level after 8 weeks of reloading. Thus our results showed that the expression of HSP72 was downregulated by HU and upregulated temporally over the level of the control during the reloading period, and they suggested that these down- and up-regulations of HSP72 may be related to many factors including mechanical stress or load applied to the muscle.

Animals↗

PubMed2003

Metabolic modulation of muscle fiber properties unrelated to mechanical stimuli.

The effects of chronically increasing (creatine-fed) or decreasing (beta-guanidinopropionic acid [beta-GPA]-fed) high-energy phosphates for up to 8 weeks on daily voluntary activity levels, swimming endurance capacity, electromyogram (EMG) activity, and the morphological and metabolic properties of single fibers in the soleus and extensor digitorum longus (EDL) muscles in young rats were determined. High-energy phosphate, voluntary activity, and soleus-integrated EMG levels were lower in beta-GPA-fed rats than in control rats. Endurance capacity was higher at a relatively low intensity of swimming and lower at a relatively high intensity in beta-GPA-fed rats than in control rats. Muscle mass and fiber size were smaller, and the percentage of slow fibers was higher in the soleus and EDL of beta-GPA-fed rats than in control rats. Succinate dehydrogenase activity was higher in both the fast and slow fibers of the EDL of beta-GPA-fed rats than in control rats. Thus, a reduction in high-energy phosphates transformed some fast fibers toward a slow phenotype. Creatine supplementation had minimal effects: The only significant change was an increase in alpha-glycerophosphate dehydrogenase activity in the fast fibers of the EDL. These results indicate that the metabolic environment of a muscle fiber can influence the prominence of a given muscle fiber independent of the activity level of muscle.

Animals↗

PubMed2003

Effects of gravitational loading on rat soleus muscle fibers following hindlimb suspension.

Effects of 16 days of hindlimb suspension and 16 days of ambulation recovery at 1-G or 2-G environment on the characteristics of soleus muscle fibers were studied in male Wistar Hannover rats. The mean cross-sectional area and myonuclear number in isolated single fibers at the termination of suspension were approximately 30% and 25% of the controls, respectively. Satellite cells were distributed evenly throughout the fiber length in the control. However, the number of satellite cells distributed at the middle of the fiber was less in the unloaded rats immediately after the termination of suspension. Both the numbers of quiescent and mitotic active satellite cell per fiber were approximately 57% less immediately after the termination of suspension than controls. The number of satellite cells at the end of fibers was increased first during the early phase of reloading. Subsequently, the number at the middle was gradually increased. The myonuclear number per fiber was also less (approximately 25%) in the unloaded than the age-matched control at the termination of suspension, but was increased following the recovery. Although the mean in vivo sarcomere length of the soleus muscle was shortened in response to plantarflexion of ankle joint, the length at the certain ankle joint angle was increased after 16 days of suspension due to sarcomere remodeling. The length at the proximal and distal, rather than the middle, portion of the fiber was stretched in both reloaded and control rats in response to dorsiflexion of the ankle joint. But it was noted that the magnitude of stretch was greater in the unloaded rats. It is suggested that the fiber end is more stimulated rapidly than the middle portion by the load applied to the muscle during the ambulation recovery.

Animals↗

PubMed2003

Changes of bone morphology in response to hindlimb suspension of rats.

Effects of chronic hindlimb suspension or exposure to 2-G from postnatal day 4 to month 3 followed by ambulation recovery on the floor on the morphology of hindlimb bones were investigated in rats. The dorsi-flexion of the ankle was inhibited in the suspended group and such phenomena were not recovered at all. The mean weight and length of femur, tibia, and fibula were less than the cage controls at the end of suspension, but gradually increased during recovery. However, they were still less than those of the age-matched controls even after 3-month recovery. External bending of shaft and rotation of distal end of tibia were observed in the suspended group and these phenomena were not recovered at all. These morphological changes caused the inhibition of dorsi-flexion of ankle joints. The electromyogram activities of ankle plantar-flexors, soleus, plantaris, lateral gastrocnemius, were inhibited and those of dorsi-flexor, tibialis anterior, were increased during suspension. Typical changes in bone morphology were not induced by exposure to 2-G. It was suggested that gravitational unloading during developing period causes irreversible inhibition of normal bone growth. It was also indicated that the suspension-related changes in bone morphology may be caused by abnormal mechanical stress due to the altered mobilization of hindlimb muscles.

Animals↗

PubMed2002

Regulation of the properties of rat hind limb muscles following gravitational unloading.

The mechanisms responsible for the morphological and metabolic adaptation of skeletal muscles to the removal of antigravity activity were investigated in rats. Significant atrophy relative to the levels before suspension was induced in ankle plantarflexsors, may be due to a reduced tension production caused by decreased muscle length and electromyogram activity. Growth failure was significant in ankle dorsiflexors, although these muscles did not atrophy. Forced muscle contraction through electrical stimulation at 1 or 100 Hz during hind limb suspension generally had detrimental effects. The percent contribution of water loss to the suspension-related change in weight was 85, 88, and 93% in soleus, plantaris, and extensor digitorum longus, respectively. The total levels of both beta-hydroxyacyl CoA dehydrogenase (HAD) and lactate dehydrogenase (LDH) were less in the suspended muscles than in the controls, having high positive correlations with the total protein content. The specific activity of HAD, but not of LDH, of the suspended muscles was lower than in the controls (25-61%). These data suggest that the cause of muscle atrophy and changes in metabolic properties may be a decreased tension development, not necessarily the reduction of electrical or contractile activity. Further, it is clearly suggested that electrical stimulation of a muscle group with different composition of fiber phenotype at a certain pattern or frequency is not suitable for the countermeasure. It is also suggested that the major cause of the decreased muscle weight was loss of water, even though protein content was also lowered after suspension. Moreover, the data suggest that the HAD level was affected more than the total protein content and LDH.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2002

Effects of long-term cold exposure on contractile muscles of rats.

The effects of 20-week cold exposure on contractile properties of soleus and extensor digitorum longus (EDL) muscles and plasma hormone levels were studied in rats. Twenty male Wistar rats (5 week old) were randomly divided into 2 groups (n = 10 each): cage-control and cold-exposed. The rats in the cold-exposed group were immersed in shoulder-deep water (approximately 18 degrees C) for 1 h/d, 5 d/week, for 20 weeks. The temperature and humidity of the animal room with 12:12 h light-dark cycle were maintained at approximately 23 degrees C and 55%, respectively. The rats were pair-fed powdered diets. The electromyogram activities in soleus and EDL were elevated by cold exposure. The body weight and absolute soleus wet weight of the cold-exposed group were significantly less than controls at the end of experiment. The one-half relaxation time and contraction time of EDL were significantly longer in the cold-exposed group than in the control group. The rate of twitch tension development, normalized by the maximum twitch tension, in EDL of the cold-exposed group was less than in the control group. Further, the fatigue resistance of EDL, but not of soleus, in response to train stimulation at 10 Hz was improved by cold exposure. The plasma levels of thyroid hormones, 3,5,3'-triiodothyronine and thyroxine, were significantly greater in cold-exposed group. Similar changes were also seen in the plasma catecholamine levels in the cold-exposed group (p > 0.05). It is suggested that long-term cold exposure causes a shift of the contractile properties of fast-twitch EDL muscle toward the slow-twitch type. The results also indicated that the characteristics of muscles responded more strongly to an increased activity level than to the elevation of plasma hormones.

Adrenal Glands↗

PubMed2002

Role of afferent input in muscle atrophy.

It is well known that soleus muscle of rat atrophies following spaceflight or hindlimb suspension (Ohira et al., 1992). It is, further, reported that the electromyogram (EMG) of soleus muscle disappears immediately in response to unloading by exposure to actual micro-g environment (Kawano et al., 2002; Leterme and Falempin, 1998) and by hindlimb suspension of rats (Alford et al., 1987; Ohira et al., 2000). However, the EMG level is increased gradually to the control level following 7-10 days of continuous hindlimb suspension (Alford et al., 1987; Ohira, 2000), while muscle atrophy is progressing (Winiarski et al., 1987). We previously reported that reduction of the EMG level of rat soleus in response to actual micro-g environment, created by a parabolic flight of a jet airplane, was closely associated with a decrease of the afferent input recorded at the L5 segmental level of spinal cord (Kawano et al., 2002). However, it is still unclear how the EMG level of soleus muscle adapts to unloading condition. The current study was performed to investigate the responses of soleus EMG and both afferent and efferent neurogram at the L5 segmental level of spinal cord to acute (20 seconds) and chronic (14 days) unloading.

Animals↗

PubMed2002

Air-righting responses to chronic hindlimb suspension and ambulation recovery in adult rats.

Laouris et al. (1990) reported that the development of air-righting in growing new-born rats was clearly suppressed when their neck and/or back rotations were prevented. Thus, it is suggested that the neck and back muscles play an important role for a quick righting in response to drop from supine position. Further, we reported that an inhibiton of posture adjustment in response to head-down drop from a height of approximately 30 cm following chronic hindlimb suspension of adult rats was accompanied by a decrease of electromyogram (EMG) activity in both neck and back muscles (Kawano et al., 2002). However, it is still unclear how the air-righting performance is influenced by hindlimb suspension in adult rats. Thus, the effects of chronic hindlimb suspension of adult rats on the patterns and time of air-righting and role of neck and back muscles in the air-righting were investigated in the current study.

Animals↗

PubMed2002

Effects of chronic hindlimb suspension on landing performance in response to head-down drop in rats.

Effects of hindlimb unloading and reloading on the patterns of landing and posture adjustment in response to head-down drop from a height of approximately 30 cm were investigated in rats. Seven weeks old male Wistar rats were hindlimb-unloaded by tail suspension for 9 consecutive weeks. Motor tests were performed immediately after the termination of suspension and recovery patterns were checked during 8 weeks of ambulation recovery. Although all of the control rats were able to land smoothly by using the four limbs as the shock absorber, the unloaded rats landed by hitting their abdomen. The hindlimb-unloaded, but not control, rats dorsi-flexed their trunk during fall. The mean angle of abdominal side was approximately 145 degrees in control and approximately 215 degrees in unloaded rats. Even though such phenomena were maintained for approximately 12 hours, the response of the trunk angle recovered significantly 2 days later. However, it was not normalized completely even after 8 weeks. Hyper-extension of ankle joints and eversion of hindlimbs at landing were also noted in the unloaded rats. These phenomena were not recovered at all. It was generally suggested that severe detrimental effects on the landing performance of rats are induced following 9-weeks of suspension. And some of the responses are irreversible.

Abdominal Muscles↗