Publications by authors named "Katsumasa Goto"

52 Publications

MBNL1-Associated Mitochondrial Dysfunction and Apoptosis in C2C12 Myotubes and Mouse Skeletal Muscle.

Int J Mol Sci 2020 Sep 2;21(17). Epub 2020 Sep 2.

Laboratory of Physiology, School of Health Science, Toyohashi SOZO University, Toyohashi 440-8511, Japan.

We explored the interrelationship between a tissue-specific alternative splicing factor muscleblind-like 1 (MBNL1) and peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α), B-cell lymphoma 2 (Bcl-2) or Bcl-2-associated X protein (Bax) in C2C12 myotubes and mouse skeletal muscle to investigate a possible physiological role of MBNL1 in mitochondrial-associated apoptosis of skeletal muscle. Expression level of PGC-1α and mitochondrial membrane potential evaluated by the fluorescence ratio of JC-1 aggregate to monomer in C2C12 myotubes were suppressed by knockdown of MBNL1. Conversely, the ratio of Bax to Bcl-2 as well as the apoptotic index in C2C12 myotubes was increased by MBNL1 knockdown. In plantaris muscle, on the other hand, not only the minimum muscle fiber diameter but also the expression level of MBNL1 and PGC-1α in of 100-week-old mice were significantly lower than that of 10-week-old mice. Furthermore, the ratio of Bax to Bcl-2 in mouse plantaris muscle was increased by aging. These results suggest that MBNL1 may play a key role in aging-associated muscle atrophy accompanied with mitochondrial dysfunction and apoptosis via mediating PGC-1α expression in skeletal muscle.
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http://dx.doi.org/10.3390/ijms21176376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503908PMC
September 2020

The Protective Effect of Brazilian Propolis against Glycation Stress in Mouse Skeletal Muscle.

Foods 2019 Sep 25;8(10). Epub 2019 Sep 25.

Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.

We investigated the protective effect of Brazilian propolis, a natural resinous substance produced by honeybees, against glycation stress in mouse skeletal muscles. Mice were divided into four groups: (1) Normal diet + drinking water, (2) Brazilian propolis (0.1%)-containing diet + drinking water, (3) normal diet + methylglyoxal (MGO) (0.1%)-containing drinking water, and (4) Brazilian propolis (0.1%)-containing diet + MGO (0.1%)-containing drinking water. MGO treatment for 20 weeks reduced the weight of the extensor digitorum longus (EDL) muscle and tended to be in the soleus muscle. Ingestion of Brazilian propolis showed no effect on this change in EDL muscles but tended to increase the weight of the soleus muscles regardless of MGO treatment. In EDL muscles, Brazilian propolis ingestion suppressed the accumulation of MGO-derived advanced glycation end products (AGEs) in MGO-treated mice. The activity of glyoxalase 1 was not affected by MGO, but was enhanced by Brazilian propolis in EDL muscles. MGO treatment increased mRNA expression of inflammation-related molecules, interleukin (IL)-1β, IL-6, and toll-like receptor 4 (TLR4). Brazilian propolis ingestion suppressed these increases. MGO and/or propolis exerted no effect on the accumulation of AGEs, glyoxalase 1 activity, and inflammatory responses in soleus muscles. These results suggest that Brazilian propolis exerts a protective effect against glycation stress by inhibiting the accumulation of AGEs, promoting MGO detoxification, and reducing proinflammatory responses in the skeletal muscle. However, these anti-glycation effects does not lead to prevent glycation-induced muscle mass reduction.
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http://dx.doi.org/10.3390/foods8100439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836237PMC
September 2019

Role of 72-kDa Heat Shock Protein in Heat-stimulated Regeneration of Injured Muscle in Rat.

J Histochem Cytochem 2019 11 24;67(11):791-799. Epub 2019 Jun 24.

Graduate School of Medicine, Osaka University, Osaka, Japan.

The regeneration of injured muscles is facilitated by intermittent heat stress. The 72-kDa heat shock protein (HSP72), the level of which is increased by heat stress, is likely involved in this effect, but the precise mechanism remains unclear. This study was conducted to investigate the localization and role(s) of HSP72 in the regenerating muscles in heat-stressed rats using immunohistochemistry. Heat stress was applied by immersion of the rat lower body into hot water (42C, 30 min, every other day) following injection of bupivacaine into the soleus muscles. After 1 week, we found that HSP72 was expressed at high levels not only in the surviving myofibers but also in the blood vessels of the regenerating muscles in heated rats. In addition, leukocytes, possibly granulocytes, expressing cluster of differentiation 43 within the blood capillaries surrounding the regenerating myofibers also highly expressed HSP72. In contrast, marked expression of HSP72 was not observed in the intact or regenerating muscles without heat stress. These results suggest that heat-stress-induced HSP72 within the myofibers, blood vessels, and circulating leukocytes may play important roles in enhancing regeneration of injured muscles by heat stress. Our findings would be useful to investigate cell-specific role(s) of HSP72 during skeletal muscle regeneration.
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http://dx.doi.org/10.1369/0022155419859861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824005PMC
November 2019

Impact of different temperature stimuli on the expression of myosin heavy chain isoforms during recovery from bupivacaine-induced muscle injury in rats.

J Appl Physiol (1985) 2019 07 23;127(1):178-189. Epub 2019 May 23.

Department of Exercise and Health Sciences, Faculty of Education, Yamaguchi University, Yamaguchi City, Yamaguchi , Japan.

Limited information exists regarding the impact of different temperature stimuli on myosin heavy chain (MyHC) expression in skeletal muscle during recovery from injury. Therefore, this experiment investigated the impact of both cold and heat exposure on the MyHC isoform profile in the rat soleus during recovery from injury. Male Wistar rats were randomly divided into control, bupivacaine-injected (BPVC), BPVC with icing, and BPVC with heat stress groups. Muscle injury was induced by intramuscular injection of bupivacaine into soleus muscles of male Wistar rats. Icing treatment (0°C for 20 min) was performed immediately after the injury. Intermittent heat stress (42°C for 30 min on alternating days) was carried out during 2-14 days after bupivacaine injection. In response to injury, a transient increase in developmental, IId/x, and IIb MyHC isoforms, as well as various types of hybrid fibers, followed by the recovery of the MyHC profile toward the control level, was noted in the regeneration of the soleus. The restoration of the MyHC profile in the regenerating muscle at whole-muscle and individual myofiber levels was partially delayed by icing but facilitated by heat stress. In addition, the application of repeated heat stress promoted the recovery of soleus muscle mass toward the control level following injury. We conclude that compared with acute and immediate cold (icing) treatment, chronic and repeated heat stress may be a more appropriate treatment for the enhancement of both normalization of the MyHC profile and restoration of muscle mass following injury. Cold exposure (icing), but not heat exposure, has been well accepted as a first-aid treatment for accidental and/or sports-related injuries. However, recent evidence suggests the negative impact of icing treatment on skeletal muscle regeneration following injury. Here, we demonstrated that acute/immediate icing treatment delayed the restoration of the myosin heavy chain (MyHC) profile, but intermittent hyperthermia, repeated for several days, facilitated the recovery of both muscle mass and the MyHC profile in the regeneration of skeletal muscle following injury.
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http://dx.doi.org/10.1152/japplphysiol.00930.2018DOI Listing
July 2019

Lactate Stimulates a Potential for Hypertrophy and Regeneration of Mouse Skeletal Muscle.

Nutrients 2019 Apr 17;11(4). Epub 2019 Apr 17.

Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Toyohashi 440-8511, Japan.

The effects of lactate on muscle mass and regeneration were investigated using mouse skeletal muscle tissue and cultured C2C12 cells. Male C57BL/6J mice were randomly divided into (1) control, (2) lactate (1 mol/L in distilled water, 8.9 mL/g body weight)-administered, (3) cardio toxin (CTX)-injected (CX), and (4) lactate-administered after CTX-injection (LX) groups. CTX was injected into right tibialis anterior (TA) muscle before the oral administration of sodium lactate (five days/week for two weeks) to the mice. Oral lactate administration increased the muscle weight and fiber cross-sectional area, and the population of Pax7-positive nuclei in mouse TA skeletal muscle. Oral administration of lactate also facilitated the recovery process of CTX-associated injured mouse TA muscle mass accompanied with a transient increase in the population of Pax7-positive nuclei. Mouse myoblast-derived C2C12 cells were differentiated for five days to form myotubes with or without lactate administration. C2C12 myotube formation with an increase in protein content, fiber diameter, length, and myo-nuclei was stimulated by lactate. These observations suggest that lactate may be a potential molecule to stimulate muscle hypertrophy and regeneration of mouse skeletal muscle via the activation of muscle satellite cells.
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http://dx.doi.org/10.3390/nu11040869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520919PMC
April 2019

Nuclear Accumulation of HSP70 in Mouse Skeletal Muscles in Response to Heat Stress, Aging, and Unloading With or Without Reloading.

Front Genet 2018 20;9:617. Epub 2018 Dec 20.

Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Japan.

The purpose of this study was to investigate the nuclear accumulation of heat shock protein 70 (HSP70), a molecular chaperonin in mouse skeletal muscle in response to aging, heat stress, and hindlimb unloading with or without reloading. Profiles of HSP70-specific nuclear transporter Hikeshi in skeletal muscles were also evaluated. Heat stress-associated nuclear accumulation of HSP70 was observed in slow soleus (SOL) and fast plantaris (PLA) muscles of young (10-week-old) mice. Mean nuclear expression level of HSP70 in slow medial gastrocnemius (MGAS) and PLA muscles of aged (100-week-old) mice increased ~4.8 and ~1.7 times, compared to that of young (10-week-old) mice. Reloading following 2-week hindlimb unloading caused accumulation of HSP70 in myonuclei in MGAS and PLA of young mice (  < 0.05). However, reloading-associated nuclear accumulation of HSP70 was not observed in both types of muscles of aged mice. On the other hand, 2-week hindlimb unloading had no impact on the nuclear accumulation of HSP70 in both muscles of young and aged mice. Nuclear expression level of Hikeshi in both MGAS and PLA in mice was suppressed by aging. No significant changes in the nuclear Hikeshi in both muscles were induced by unloading with or without reloading. Results of this study indicate that the nuclear accumulation of HSP70 might show a protective response against cellular stresses in skeletal muscle and that the protective response may be suppressed by aging. Protective response to aging might depend on muscle fiber types.
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http://dx.doi.org/10.3389/fgene.2018.00617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307543PMC
December 2018

Effect of a combination of astaxanthin supplementation, heat stress, and intermittent reloading on satellite cells during disuse muscle atrophy.

J Zhejiang Univ Sci B 2018 Nov.;19(11):844-852

Hirosaki Gakuin University, Hirosaki, Aomori 036-8577, Japan.

We examined the effect of a combination of astaxanthin (AX) supplementation, repeated heat stress, and intermittent reloading (IR) on satellite cells in unloaded rat soleus muscles. Forty-nine male Wistar rats (8-week-old) were divided into control, hind-limb unweighting (HU), IR during HU, IR with AX supplementation, IR with repeated heat stress (41.0-41.5 °C for 30 min), and IR with AX supplementation and repeated heat stress groups. After the experimental period, the antigravitational soleus muscle was analyzed using an immunohistochemical technique. Our results revealed that the combination of dietary AX supplementation and heat stress resulted in protection against disuse muscle atrophy in the soleus muscle. This protective effect may be partially due to a higher satellite cell number in the atrophied soleus muscle in the IR/AX/heat stress group compared with the numbers found in the other groups. We concluded that the combination treatment with dietary AX supplementation and repeated heat stress attenuates soleus muscle atrophy, in part by increasing the number of satellite cells.
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http://dx.doi.org/10.1631/jzus.B1800076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238114PMC
February 2019

Activation of adiponectin receptors has negative impact on muscle mass in C2C12 myotubes and fast-type mouse skeletal muscle.

PLoS One 2018 11;13(10):e0205645. Epub 2018 Oct 11.

Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan.

This study investigated the effects of AdipoRon, which is an agonist for adiponectin receptor 1 (AdipoR1) and AdipoR2, on the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells and skeletal muscle mass in C57BL/6J mice. AdipoRon suppressed the protein content, myotube diameter, and number of nuclei per myotube of C2C12 cells of C2C12 myotubes in a dose-dependent manner. Adiponectin-associated decline of protein content, diameter, and number of nuclei per myotube in C2C12 myotubes was partially rescued by knockdown of AdipoR1 and/or AdipoR2. Phosphorylation level of AMPK showed a trend to be increased by AdipoRon. A significant increase in phosphorylation level of AMPK was observed at 20 μM AdipoRon. Knockdown of AdipoR1 and/or AdipoR2 rescued AdipoRon-associated decrease in protein content of C2C12 myotubes. AdipoRon-associated increase in phosphorylation level of AMPK in C2C12 myotubes was suppressed by knockdown of AdipoR1 and/or AdipoR2. Successive intravenous injections of AdipoRon into mice caused a decrease in the wet weight of plantaris muscle (PLA), but not in soleus muscle (SOL). Mean fiber cross-sectional area of PLA, but not of SOL, was significantly decreased by AdipoRon administration. On the one hand, the expression level of phosphorylated AMPK and ubiquitinated protein in SOL and PLA muscles was upregulated by AdipoRon administration. On the other hand, AdipoRon administration induced no changes in the expression level of puromycin-labeled proteins in both SOL and PLA muscles. Expression level of adiponectin in extensor digitorum longus (EDL) muscle was increased by aging, but not in SOL muscle. Aging had no effect on the expression level of AdipoR1 and AdipoR2 in both muscles. Phosphorylation level of AMPK in EDL was increased by aging, but not SOL muscle. Results from this study suggest that high level of circulating adiponectin may induce skeletal muscle atrophy, especially fast-type muscle.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205645PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181411PMC
March 2019

AMPK Mediates Muscle Mass Change But Not the Transition of Myosin Heavy Chain Isoforms during Unloading and Reloading of Skeletal Muscles in Mice.

Int J Mol Sci 2018 Sep 27;19(10). Epub 2018 Sep 27.

Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi 440-8511, Japan.

5'AMP-activated protein kinase (AMPK) plays an important role in the regulation of skeletal muscle mass and fiber-type distribution. However, it is unclear whether AMPK is involved in muscle mass change or transition of myosin heavy chain (MyHC) isoforms in response to unloading or increased loading. Here, we checked whether AMPK controls muscle mass change and transition of MyHC isoforms during unloading and reloading using mice expressing a skeletal-muscle-specific dominant-negative AMPKα1 (AMPK-DN). Fourteen days of hindlimb unloading reduced the soleus muscle weight in wild-type and AMPK-DN mice, but reduction in the muscle mass was partly attenuated in AMPK-DN mice. There was no difference in the regrown muscle weight between the mice after 7 days of reloading, and there was concomitantly reduced AMPKα2 activity, however it was higher in AMPK-DN mice after 14 days reloading. No difference was observed between the mice in relation to the levels of slow-type MyHC I, fast-type MyHC IIa/x, and MyHC IIb isoforms following unloading and reloading. The levels of 72-kDa heat-shock protein, which preserves muscle mass, increased in AMPK-DN-mice. Our results indicate that AMPK mediates the progress of atrophy during unloading and regrowth of atrophied muscles following reloading, but it does not influence the transition of MyHC isoforms.
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http://dx.doi.org/10.3390/ijms19102954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212939PMC
September 2018

[A case of mitochondrial disease with multiple mitochondrial DNA deletions suspected amyotrophic lateral sclerosis-frontotemporal dementia].

Rinsho Shinkeigaku 2018 Jan 22;58(1):15-20. Epub 2017 Dec 22.

Department of Neurology, Nanpu Hospital.

A 76-year-old woman showed a dramatic lowering of her tone of voice in October 2014, followed by muscle weakness of the left arm. The previous attending physician noticed remarkable left dominant frontotemporal lobe atrophy on cranial MRI. Her dysarthria, dysphagia and the muscle weakness of her extremities worsened, and a muscle biopsy revealed mitochondrial abnormality. The mitochondrial DNA from her muscle showed multiple deletions; the previous physician therefore diagnosed the patient with mitochondrial disease. The patient resembled amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD). No other cases of ALS-FTD with mitochondrial disease have been reported in Japan. We therefore consider the present case to be valuable.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001071DOI Listing
January 2018

Long Term Changes in Muscles around the Knee Joint after ACL Resection in Rats: Comparisons of ACL-Resected, Contralateral and Normal Limb.

J Sports Sci Med 2017 Sep 8;16(3):429-437. Epub 2017 Aug 8.

Department of Sports Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.

The purpose of this study was to investigate the long-term effects of anterior cruciate ligament (ACL) resection on the morphological and contractile characteristics of rectus femoris (RF) and semimembranosus (SM) muscles in both injured and contralateral hindlimbs in rats. Wistar male rats (8-week old) were used. No ACL-resection-associated changes in the mass of both muscles were observed 1 week after ACL resection. On the other hand, ACL-resection-associated reduction on mean fiber cross-sectional area (fiber CSA) in RF muscle lasted 48 weeks after ACL resection. Furthermore, ACL-resection associated increase in fiber composition of type I fiber in RF muscle in contralateral limbs. In addition, long-term effects of ACL resection were observed in both ACL-resected and contralateral limbs. Evidences from this study suggested that ACL resection may cause to change in the morphological (fiber CSA) and contractile (distribution of fiber types) properties of skeletal muscles around the knee joint in not only injured but also contralateral limb. Rehabilitation for quantitative and qualitative muscle changes by ACL resection may be required a special care for a long-term period.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592296PMC
September 2017

Potential involvement of dietary advanced glycation end products in impairment of skeletal muscle growth and muscle contractile function in mice.

Br J Nutr 2017 01 17;117(1):21-29. Epub 2017 Jan 17.

1Laboratory of Sports and Exercise Medicine,Graduate School of Human and Environmental Studies,Kyoto University,Kyoto,606-8501,Japan.

Diets enriched with advanced glycation end products (AGE) have recently been related to muscle dysfunction processes. However, it remains unclear whether long-term exposure to an AGE-enriched diet impacts physiological characteristics of skeletal muscles. Therefore, we explored the differences in skeletal muscle mass, contractile function and molecular responses between mice receiving a diet high in AGE (H-AGE) and low in AGE (L-AGE) for 16 weeks. There were no significant differences between L-AGE and H-AGE mice with regard to body weight, food intake or epididymal fat pad weight. However, extensor digitorum longus (EDL) and plantaris (PLA) muscle weights in H-AGE mice were lower compared with L-AGE mice. Higher levels of N ε -(carboxymethyl)-l-lysine, a marker for AGE, in EDL muscles of H-AGE mice were observed compared with L-AGE mice. H-AGE mice showed lower muscle strength and endurance in vivo and lower muscle force production of PLA muscle in vitro. mRNA expression levels of myogenic factors including myogenic factor 5 and myogenic differentiation in EDL muscle were lower in H-AGE mice compared with L-AGE mice. The phosphorylation status of 70-kDa ribosomal protein S6 kinase Thr389, an indicator of protein synthesis signalling, was lower in EDL muscle of H-AGE mice than that of L-AGE mice. These findings suggest that long-term exposure to an AGE-enriched diet impairs skeletal muscle growth and muscle contractile function, and that these muscle dysfunctions may be attributed to the inhibition of myogenic potential and protein synthesis.
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http://dx.doi.org/10.1017/S0007114516004591DOI Listing
January 2017

Suppression of Myostatin Stimulates Regenerative Potential of Injured Antigravitational Soleus Muscle in Mice under Unloading Condition.

Int J Med Sci 2016 10;13(9):680-5. Epub 2016 Aug 10.

Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan;; Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan.

Effects of myostatin (MSTN)-suppression on the regeneration of injured skeletal muscle under unloading condition were investigated by using transgenic mice expressing a dominant-negative form of MSTN (MSTN-DN). Both MSTN-DN and wild-type (WT) mice were subjected to continuous hindlimb suspension (HS) for 6 weeks. Cardiotoxin (CTX) was injected into left soleus muscle under anesthesia 2 weeks after the initiation of HS. Then, the soleus muscles were excised following 6-week HS (4 weeks after CTX-injection). CTX-injection caused to reduce the soleus fiber cross-sectional area (CSA) in WT mice under both unloading and weight-bearing conditions, but not in MSTN-DN mice. Under unloading condition, CTX-injected muscle weight and fiber CSA in MSTN-DN mice were significantly higher than those in WT mice. CTX-injected muscle had many damaged and regenerating fibers having central nuclei in both WT and MSTN-DN mice. Significant increase in the population of Pax7-positive nuclei in CTX-injected muscle was observed in MSTN-DN mice, but not in WT mice. Evidences indicate that the suppression of MSTN cause to increase the regenerative potential of injured soleus muscle via the increase in the population of muscle satellite cells regardless of unloading conditions.
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http://dx.doi.org/10.7150/ijms.16267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027186PMC
March 2017

Isolation, Cryosection and Immunostaining of Skeletal Muscle.

Methods Mol Biol 2016 ;1460:85-100

Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, UK.

Adult skeletal muscle is maintained and repaired by resident stem cells called satellite cells, located between the plasmalemma of a muscle fiber, and the surrounding basal lamina. When needed, satellite cells are activated to form proliferative myoblasts, that then differentiate and fuse to existing muscle fibers, or fuse together to form replacement myofibers. In parallel, a proportion of satellite cells self-renew, to maintain the stem cell pool. To date, Pax7 is the marker of choice for identifying quiescent satellite cells. Co-immunostaining of skeletal muscle with Pax7 and laminin allows both identification of satellite cells, and the myofiber that they are associated with. Furthermore, satellite cells can be followed through the early stages of the myogenic program by co-immunostaining with myogenic regulatory factors such as MyoD. To test genetically modified mice for satellite cell expression, co-immunostaining can be performed for Pax7 and reporter genes such as eGFP. Here, we describe a method for identification of satellite cells in skeletal muscle sections, including muscle isolation, cryosectioning and co-immunostaining for Pax7 and laminin.
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http://dx.doi.org/10.1007/978-1-4939-3810-0_8DOI Listing
January 2018

Astaxanthin intake attenuates muscle atrophy caused by immobilization in rats.

Physiol Rep 2016 08;4(15)

Department of Exercise and Health Sciences, Faculty of Education, Yamaguchi University, Yamaguchi City, Yamaguchi, Japan

Astaxanthin is a carotenoid pigment and has been shown to be an effective inhibitor of oxidative damage. We tested the hypothesis that astaxanthin intake would attenuate immobilization-induced muscle atrophy in rats. Male Wistar rats (14-week old) were fed for 24 days with either astaxanthin or placebo diet. After 14 days of each experimental diet intake, the hindlimb muscles of one leg were immobilized in plantar flexion position using a plaster cast. Following 10 days of immobilization, both the atrophic and the contralateral plantaris muscles were removed and analyzed to determine the level of muscle atrophy along with measurement of the protein levels of CuZn-superoxide dismutase (CuZn-SOD) and selected proteases. Compared with placebo diet animals, the degree of muscle atrophy in response to immobilization was significantly reduced in astaxanthin diet animals. Further, astaxanthin supplementation significantly prevented the immobilization-induced increase in the expression of CuZn-SOD, cathepsin L, calpain, and ubiquitin in the atrophied muscle. These results support the postulate that dietary astaxanthin intake attenuates the rate of disuse muscle atrophy by inhibiting oxidative stress and proteolysis via three major proteolytic pathways.
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http://dx.doi.org/10.14814/phy2.12885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985550PMC
August 2016

Dietary astaxanthin supplementation attenuates disuse-induced muscle atrophy and myonuclear apoptosis in the rat soleus muscle.

J Physiol Sci 2017 Jan 27;67(1):181-190. Epub 2016 Apr 27.

Faculty of Education, Yamaguchi University, 1677-1 Yoshida, Yamaguchi, Japan.

Extended periods of skeletal muscle disuse results in muscle atrophy and weakness. Currently, no therapeutic treatment is available for the prevention of this problem. Nonetheless, growing evidence suggests that prevention of disuse-induced oxidative stress in inactive muscle fibers can delay inactivity-induced muscle wasting. Therefore, this study tested the hypothesis that dietary supplementation with the antioxidant astaxanthin would protect against disuse muscle atrophy, in part, by prevention of myonuclear apoptosis. Wistar rats (8 weeks old) were divided into control (CT, n = 9), hindlimb unloading (HU, n = 9), and hindlimb unloading with astaxanthin (HU + AX, n = 9) groups. Following 2 weeks of dietary supplementation, rats in the HU and HU + AX groups were exposed to unloading for 7 days. Seven-day unloading resulted in reduced soleus muscle weight and myofiber cross-sectional area (CSA) by ~30 and ~47 %, respectively. Nonetheless, relative muscle weights and CSA of the soleus muscle in the HU + AX group were significantly greater than those of the HU group. Moreover, astaxanthin prevented disuse-induced increase in the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei. We conclude that astaxanthin supplementation prior to and during hindlimb unloading attenuates soleus muscle atrophy, in part, by suppressing myonuclear apoptosis.
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http://dx.doi.org/10.1007/s12576-016-0453-4DOI Listing
January 2017

Heat stress acutely activates insulin-independent glucose transport and 5'-AMP-activated protein kinase prior to an increase in HSP72 protein in rat skeletal muscle.

Physiol Rep 2015 Nov;3(11)

Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan

Heat stress (HS) stimulates heat shock protein (HSP) 72 mRNA expression, and the period after an increase in HSP72 protein is characterized by enhanced glucose metabolism in skeletal muscle. We have hypothesized that, prior to an increase in the level of HSP72 protein, HS activates glucose metabolism by acutely stimulating 5'-AMP-activated protein kinase (AMPK). Rat epitrochlearis muscle was isolated and incubated either with or without HS (42°C) for 10 and 30 min. HS for 30 min led to an increase in the level of Hspa1a and Hspa1b mRNA but did not change the amount of HSP72 protein. However, HS for both 10 and 30 min led to a significant increase in the rate of 3-O-methyl-d-glucose (3MG) transport, and the stimulatory effect of 3MG transport was completely blocked by cytochalasin B. HS-stimulated 3MG transport was also inhibited by dorsomorphin but not by wortmannin. HS led to a decrease in the concentration of ATP, phosphocreatine, and glycogen, to an increase in the level of phosphorylation of AMPKα Thr(172), and to an increase in the activity of both AMPKα1 and AMPKα2. HS did not affect the phosphorylation status of insulin receptor signaling or Ca(2+)/calmodulin-dependent protein kinase II. These results suggest that HS acts as a rapid stimulator of insulin-independent glucose transport, at least in part by stimulating AMPK via decreased energy status. Although further research is warranted, heat treatment of skeletal muscle might be a promising method to promote glucose metabolism acutely.
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http://dx.doi.org/10.14814/phy2.12601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632964PMC
November 2015

Involvement of AMPK in regulating slow-twitch muscle atrophy during hindlimb unloading in mice.

Am J Physiol Endocrinol Metab 2015 Oct 4;309(7):E651-62. Epub 2015 Aug 4.

Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan;

AMPK is considered to have a role in regulating skeletal muscle mass. However, there are no studies investigating the function of AMPK in modulating skeletal muscle mass during atrophic conditions. In the present study, we investigated the difference in unloading-associated muscle atrophy and molecular functions in response to 2-wk hindlimb suspension between transgenic mice overexpressing the dominant-negative mutant of AMPK (AMPK-DN) and their wild-type (WT) littermates. Male WT (n = 24) and AMPK-DN (n = 24) mice were randomly divided into two groups: an untreated preexperimental control group (n = 12 in each group) and an unloading (n = 12 in each group) group. The relative soleus muscle weight and fiber cross-sectional area to body weight were decreased by ∼30% in WT mice by hindlimb unloading and by ∼20% in AMPK-DN mice. There were no changes in puromycin-labeled protein or Akt/70-kDa ribosomal S6 kinase signaling, the indicators of protein synthesis. The expressions of ubiquitinated proteins and muscle RING finger 1 mRNA and protein, markers of the ubiquitin-proteasome system, were increased by hindlimb unloading in WT mice but not in AMPK-DN mice. The expressions of molecules related to the protein degradation system, phosphorylated forkhead box class O3a, inhibitor of κBα, microRNA (miR)-1, and miR-23a, were decreased only in WT mice in response to hindlimb unloading, and 72-kDa heat shock protein expression was higher in AMPK-DN mice than in WT mice. These results imply that AMPK partially regulates unloading-induced atrophy of slow-twitch muscle possibly through modulation of the protein degradation system, especially the ubiquitin-proteasome system.
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http://dx.doi.org/10.1152/ajpendo.00165.2015DOI Listing
October 2015

Microcurrent electrical neuromuscular stimulation facilitates regeneration of injured skeletal muscle in mice.

J Sports Sci Med 2015 Jun 8;14(2):297-303. Epub 2015 May 8.

Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University , Toyohashi, Aichi, Japan ; Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University , Toyohashi, Aichi, Japan.

Conservative therapies, mainly resting care for the damaged muscle, are generally used as a treatment for skeletal muscle injuries (such as muscle fragmentation). Several past studies reported that microcurrent electrical neuromuscular stimulation (MENS) facilitates a repair of injured soft tissues and shortens the recovery period. However, the effects of MENS on the regeneration in injured skeletal muscle are still unclear. The purpose of this study was to investigate the effect of MENS on the regenerative process of injured skeletal muscle and to elucidate whether satellite cells in injured skeletal muscle are activated by MENS by using animal models. Male C57BL/6J mice, aged 7 weeks old, were used (n = 30). Mice were randomly divided into two groups: (1) cardiotoxin (CTX)-injected (CX, n = 15) and (2) CTX-injected with MENS treatment (MX, n=15) groups. CTX was injected into tibialis anterior muscle (TA) of mice in CX and MX groups to initiate the necrosis-regeneration cycle of the muscle. TA was dissected 1, 2, and 3 weeks after the injection. Muscle weight, muscle protein content, the mean cross-sectional areas of muscle fibers, the relative percentage of fibers having central nuclei, and the number of muscle satellite cells were evaluated. MENS facilitated the recovery of the muscle dry weight and protein content relative to body weight, and the mean cross-sectional areas of muscle fibers in CTX-induced injured TA muscle. The number of Pax7-positive muscle satellite cells was increased by MENS during the regenerating period. Decrease in the percentages of fibers with central nuclei after CTX-injection was facilitated by MENS. MENS may facilitate the regeneration of injured skeletal muscles by activating the regenerative potential of skeletal muscles. Key pointsMicrocurrent electrical neuromuscular stimulation (MENS) facilitated the recovery of the relative muscle dry weight, the relative muscle protein content, and the mean cross-sectional areas of muscle fibers of injured TA muscle in mice.The number of satellite cells was increased by MENS during the regenerating phase of injured skeletal muscle.Decrease in the percentages of fibers with central nuclei was facilitated by MENS.MENS may facilitate the regeneration of injured skeletal muscles.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424458PMC
June 2015

Responses of skeletal muscles to gravitational unloading and/or reloading.

J Physiol Sci 2015 Jul 8;65(4):293-310. Epub 2015 Apr 8.

Space Biomedical Research Office, Japan Aerospace Exploration Agency, Tsukuba, Ibaraki, 305-8505, Japan.

Adaptation of morphological, metabolic, and contractile properties of skeletal muscles to inhibition of antigravity activities by exposure to a microgravity environment or by simulation models, such as chronic bedrest in humans or hindlimb suspension in rodents, has been well reported. Such physiological adaptations are generally detrimental in daily life on earth. Since the development of suitable countermeasure(s) is essential to prevent or inhibit these adaptations, effects of neural, mechanical, and metabolic factors on these properties in both humans and animals were reviewed. Special attention was paid to the roles of the motoneurons (both efferent and afferent neurograms) and electromyogram activities as the neural factors, force development, and/or length of sarcomeres as the mechanical factors and mitochondrial bioenergetics as the metabolic factors.
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http://dx.doi.org/10.1007/s12576-015-0375-6DOI Listing
July 2015

Loading-associated expression of TRIM72 and caveolin-3 in antigravitational soleus muscle in mice.

Physiol Rep 2014 Dec 24;2(12). Epub 2014 Dec 24.

Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Toyohashi, 440-8511, Japan Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, 440-8511, Japan.

Effects of mechanical loading on the expression level of tripartite motif-containing 72 (TRIM72) and caveolin-3 (Cav-3) in mouse soleus muscle were investigated. Mice were subjected to (1) continuous hindlimb suspension (HS) for 2 weeks followed by 1-week ambulation recovery or (2) functional overloading (FO) on the soleus by cutting the distal tendons of the plantaris and gastrocnemius muscles. Soleus muscle atrophy was induced by 2-week hindlimb suspension (HS). Reloading-associated regrowth of atrophied soleus muscle was observed by 1-week reloading following HS. HS also depressed the expression level of insulin receptor substrate-1 (IRS-1) mRNA, TRIM72, Cav-3, and phosphorylated Akt (p-Akt)/total Akt (t-Akt), but increased the phosphorylated level of p38 mitogen-activated protein kinase (p-p38MAPK) in soleus muscle. Thereafter, the expression level of MyoD mRNA, TRIM72 (mRNA, and protein), and Cav-3 was significantly increased and recovered to the basal level during 1-week reloading after HS. Although IRS-1 expression was also upregulated by reloading, the expression level was significantly lower than that before HS. Significant increase in p-Akt and phosphorylated p70 S6 kinase (p-p70S6K) was observed by 1-day reloading. On the other hand, 1-week functional overloading (FO) induced soleus muscle hypertrophy. In FO-associated hypertrophied soleus muscle, the expression level of IRS-1 mRNA, MyoD mRNA, TRIM72 mRNA, p-Akt, and p-p70S6K was increased, but the expression of Cav-3 and p-p38MAPK was decreased. FO had no effect on the protein expression level of TRIM72. These observations suggest that the loading-associated upregulation of TRIM72 protein in skeletal muscle may depress the regrowth of atrophied muscle via a partial suppression of IRS-1. In addition, downregulation of Cav-3 in skeletal muscle may depress overloading-induced muscle hypertrophy.
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http://dx.doi.org/10.14814/phy2.12259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4332229PMC
December 2014

Effects of gravitational loading levels on protein expression related to metabolic and/or morphologic properties of mouse neck muscles.

Physiol Rep 2014 Jan 13;2(1):e00183. Epub 2014 Jan 13.

Research Center for Adipocyte and Muscle Science, Doshisha University, Kyotanabe City, 610-0394, Kyoto, Japan.

The effects of 3 months of spaceflight (SF), hindlimb suspension, or exposure to 2G on the characteristics of neck muscle in mice were studied. Three 8-week-old male C57BL/10J wild-type mice were exposed to microgravity on the International Space Station in mouse drawer system (MDS) project, although only one mouse returned to the Earth alive. Housing of mice in a small MDS cage (11.6 × 9.8-cm and 8.4-cm height) and/or in a regular vivarium cage was also performed as the ground controls. Furthermore, ground-based hindlimb suspension and 2G exposure by using animal centrifuge (n = 5 each group) were performed. SF-related shift of fiber phenotype from type I to II and atrophy of type I fibers were noted. Shift of fiber phenotype was related to downregulation of mitochondrial proteins and upregulation of glycolytic proteins, suggesting a shift from oxidative to glycolytic metabolism. The responses of proteins related to calcium handling, myofibrillar structure, and heat stress were also closely related to the shift of muscular properties toward fast-twitch type. Surprisingly, responses of proteins to 2G exposure and hindlimb suspension were similar to SF, although the shift of fiber types and atrophy were not statistically significant. These phenomena may be related to the behavior of mice that the relaxed posture without lifting their head up was maintained after about 2 weeks. It was suggested that inhibition of normal muscular activities associated with gravitational unloading causes significant changes in the protein expression related to metabolic and/or morphological properties in mouse neck muscle.
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http://dx.doi.org/10.1002/phy2.183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967672PMC
January 2014

AICAR-induced activation of AMPK negatively regulates myotube hypertrophy through the HSP72-mediated pathway in C2C12 skeletal muscle cells.

Am J Physiol Endocrinol Metab 2014 Feb 17;306(3):E344-54. Epub 2013 Dec 17.

Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Toyohashi, Japan;

5'-AMP-activated protein kinase (AMPK) plays an important role as a negative regulator of skeletal muscle mass. However, the precise mechanism of AMPK-mediated regulation of muscle mass is not fully clarified. Heat shock proteins (HSPs), stress-induced molecular chaperones, are related with skeletal muscle adaptation, but the association between AMPK and HSPs in skeletal muscle hypertrophy is unknown. Thus, we investigated whether AMPK regulates hypertrophy by mediating HSPs in C2C12 cells. The treatment with AICAR, a potent stimulator of AMPK, decreased 72-kDa HSP (HSP72) expression, whereas there were no changes in the expressions of 25-kDa HSP, 70-kDa heat shock cognate, and heat shock transcription factor 1 in myotubes. Protein content and diameter were less in the AICAR-treated myotubes in those without treatment. AICAR-induced suppression of myotube hypertrophy and HSP72 expression was attenuated in the siRNA-mediated AMPKα knockdown myotubes. AICAR increased microRNA (miR)-1, a modulator of HSP72, and the increase of miR-1 was not induced in AMPKα knockdown condition. Furthermore, siRNA-mediated HSP72 knockdown blocked AICAR-induced inhibition of myotube hypertrophy. AICAR upregulated the gene expression of muscle Ring-finger 1, and this alteration was suppressed in either AMPKα or HSP72 knockdown myotubes. The phosphorylation of p70 S6 kinase Thr(389) was downregulated by AICAR, whereas this was attenuated in AMPKα, but not in HSP72, knockdown myotubes. These results suggest that AMPK inhibits hypertrophy through, in part, an HSP72-associated mechanism via miR-1 and protein degradation pathways in skeletal muscle cells.
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http://dx.doi.org/10.1152/ajpendo.00495.2013DOI Listing
February 2014

Up-regulation of adiponectin expression in antigravitational soleus muscle in response to unloading followed by reloading, and functional overloading in mice.

PLoS One 2013 6;8(12):e81929. Epub 2013 Dec 6.

Department of Physiology, Graduate School of Health Sciences, Toyohashi SOZO University, Aichi, Japan.

The purpose of this study was to investigate the expression level of adiponectin and its related molecules in hypertrophied and atrophied skeletal muscle in mice. The expression was also evaluated in C2C12 myoblasts and myotubes. Both mRNA and protein expression of adiponectin, mRNA expression of adiponectin receptor (AdipoR) 1 and AdipoR2, and protein expression of adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif 1 (APPL1) were observed in C2C12 myoblasts. The expression levels of these molecules in myotubes were higher than those in myoblasts. The expression of adiponectin-related molecules in soleus muscle was observed at mRNA (adiponectin, AdipoR1, AdipoR2) and protein (adiponectin, APPL1) levels. The protein expression levels of adiponectin and APPL1 were up-regulated by 3 weeks of functional overloading. Down-regulation of AdipoR1 mRNA, but not AdipoR2 mRNA, was observed in atrophied soleus muscle. The expression of adiponectin protein, AdipoR1 mRNA, and APPL1 protein was up-regulated during regrowth of unloading-associated atrophied soleus muscle. Mechanical loading, which could increase skeletal muscle mass, might be a useful stimulus for the up-regulations of adiponectin and its related molecules in skeletal muscle.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081929PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855747PMC
September 2014

Regeneration of injured skeletal muscle in heat shock transcription factor 1-null mice.

Physiol Rep 2013 Aug 29;1(3):e00071. Epub 2013 Aug 29.

Department of Orthopaedic Surgery, St. Marianna University School of Medicine Kawasaki, Japan.

The purpose of this study was to investigate a role of heat shock transcription factor 1 (HSF1)-mediated stress response during regeneration of injured soleus muscle by using HSF1-null mice. Cardiotoxin (CTX) was injected into the left muscle of male HSF1-null and wild-type mice under anesthesia with intraperitoneal injection of pentobarbital sodium. Injection of physiological saline was also performed into the right muscle. Soleus muscles were dissected bilaterally 2 and 4 weeks after the injection. The relative weight and fiber cross-sectional area in CTX-injected muscles of HSF1-null, not of wild-type, mice were less than controls with injection of physiological saline 4 weeks after the injury, indicating a slower regeneration. Injury-related increase of Pax7-positive muscle satellite cells in HSF1-null mice was inhibited versus wild-type mice. HSF1-deficiency generally caused decreases in the basal expression levels of heat shock proteins (HSPs). But the mRNA expression levels of HSP25 and HSP90α in HSF1-null mice were enhanced in response to CTX-injection, compared with wild-type mice. Significant up-regulations of proinflammatory cytokines, such as interleukin (IL) -6, IL-1β, and tumor necrosis factor mRNAs, with greater magnitude than in wild-type mice were observed in HSF1-deficient mouse muscle. HSF1 and/or HSF1-mediated stress response may play a key role in the regenerating process of injured skeletal muscle. HSF1 deficiency may depress the regenerating process of injured skeletal muscle via the partial depression of increase in Pax7-positive satellite cells. HSF1-deficiency-associated partial depression of skeletal muscle regeneration might also be attributed to up-regulation of proinflammatory cytokines.
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http://dx.doi.org/10.1002/phy2.71DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835021PMC
August 2013

Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.

PLoS One 2013 22;8(10):e77788. Epub 2013 Oct 22.

Department of Orthopaedic Surgery, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.

Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (p<0.05). Significant up-regulations of interleukin (IL)-1β and tumor necrosis factor mRNAs were observed in HSF1-null, but not in wild-type, mice following 2 weeks of overloading. Overloading-related increases of IL-6 and AFT3 mRNA expressions seen after 2 weeks of overloading tended to decrease after 4 weeks in both types of mice. In HSF1-null mice, however, the significant overloading-related increase in the expression of IL-6, not ATF3, mRNA was noted even at 4th week. Inhibition of muscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0077788PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805596PMC
May 2014

Microcurrent electrical nerve stimulation facilitates regrowth of mouse soleus muscle.

Int J Med Sci 2013 7;10(10):1286-94. Epub 2013 Aug 7.

Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Toyohashi, Aichi, Japan.

Microcurrent electrical nerve stimulation (MENS) has been used to facilitate recovery from skeletal muscle injury. However, the effects of MENS on unloading-associated atrophied skeletal muscle remain unclear. Effects of MENS on the regrowing process of unloading-associated atrophied skeletal muscle were investigated. Male C57BL/6J mice (10-week old) were randomly assigned to untreated normal recovery (C) and MENS-treated (M) groups. Mice of both groups are subjected to continuous hindlimb suspension (HS) for 2 weeks followed by 7 days of ambulation recovery. Mice in M group were treated with MENS for 60 min 1, 3, and 5 days following HS, respectively, under anesthesia. The intensity, the frequency, and the pulse width of MENS were set at 10 μA, 0.3 Hz, and 250 msec, respectively. Soleus muscles were dissected before and immediately after, 1, 3 and 7 days after HS. Soleus muscle wet weight and protein content were decreased by HS. The regrowth of atrophied soleus muscle in M group was faster than that in C group. Decrease in the reloading-induced necrosis of atrophied soleus was facilitated by MENS. Significant increases in phosphorylated levels of p70 S6 kinase and protein kinase B (Akt) in M group were observed, compared with C group. These observations are consistent with that MENS facilitated regrowth of atrophied soleus muscle. MENS may be a potential extracellular stimulus to activate the intracellular signals involved in protein synthesis.
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http://dx.doi.org/10.7150/ijms.5985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3752717PMC
March 2014

Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

PLoS One 2012 9;7(7):e40112. Epub 2012 Jul 9.

Behavioural Neuroscience Section, Cellular Biology and Neuroscience Department, Istituto Superiore di Sanità, Rome, Italy.

Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occurred only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040112PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392276PMC
March 2013

Effects of heat stress on muscle mass and the expression levels of heat shock proteins and lysosomal cathepsin L in soleus muscle of young and aged mice.

Mol Cell Biochem 2012 Oct 24;369(1-2):45-53. Epub 2012 Jun 24.

Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Toyohashi, Japan.

Effects of heat stress on skeletal muscle mass in young and aged mice were investigated. Young (7-week) and aged (106-week) male C57BL/6J mice were randomly assigned to control and heat-stressed groups in each age. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anesthesia. Seven days after the exposure, soleus muscles were dissected from both hindlimbs. Protein content and the relative composition of Type II fibers in aged soleus were lower than those in young muscle. In aged soleus, higher baseline expression levels of HSP25, HSP72, and cathepsin L were observed compared with those in young muscle (p < 0.05). However, there were no significant differences in the expression levels of phosphorylated p70 S6 kinase (p-p70S6K), calpain 1, and calpain 2 of soleus between two age groups. A significant increase in muscle mass of both age groups was induced by heat stress (p < 0.05). Heat stress also upregulated the expressions of HSP25, HSP72, and p-p70S6K in both ages (p < 0.05). On the other hand, a significant decrease in cathepsin L expression by heating was observed in aged soleus, but not in young (p < 0.05). Both the percentage of Type I fibers and the expression of calpains in both age groups were unchanged following heat stress. Heat stress-associated downregulation of cathepsin L may be attributed to the upregulation of HSP72, which stabilizes lysosomal membranes (p < 0.05). Upregulations of HSP25, HSP72, and p-p70S6K and/or the downregulation of cathepsin L may play a role in heat stress-associated muscle hypertrophy in aged soleus muscle.
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http://dx.doi.org/10.1007/s11010-012-1367-yDOI Listing
October 2012

[Intravascular large B-cell lymphoma with low signal intensity lesions on T2 weighted spinal magnetic resonance image that were suspected to be hemorrhages].

Rinsho Shinkeigaku 2012 ;52(5):344-50

Department of Neurology, Nishibeppu National Hospital.

A 79-year-old female had a spinal lesion that was definitely diagnosed as intravascular large B-cell lymphoma on the basis of skin biopsy findings, and she was treated by rituximab-containing chemotherapy. The spinal lesion showed high and low signal intensities on T₂ weighted magnetic resonance imaging (MRI) scans, those low signal intensity lesions were suspected to be hemorrhages. The hemorrhages were thought to have been caused by interaction between atypical lymphoma cells and the endothelial cells of spinal blood vessels, by hemorrhagic infarction or by rupture of the capillary endothelium due to interaction between rituximab and lymphoma cells. Intravascular large B-cell lymphoma cases rarely show low signal intensity on spinal T₂ weighted MRI scans.
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http://dx.doi.org/10.5692/clinicalneurol.52.344DOI Listing
March 2013