• Journal of Life Science
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• v.14 no.5
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• pp.741-746
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• 2004

This study investigated the response of GLUT-4 and GRP-78 protein expression in soleus muscle of Streptozotocin-induced diabetic rats with caffeine oral administration by imposing different exercise intensities. Rats were randomly divided into 5 groups (n=6 in each group): diabetic group (D), diabetic-caffeine group (DC), diabetic-caffeine group with low intensity exercise (DCL), diabetic-caffeine group with moderate intensity exercise (DCM) and diabetic-caffeine group with high intensity exercise (DCH). The rats in DCL, DCM and DCH groups were exercised acutely by treadmill running for 8 meter/m, 16 meter/m and 25 meter/m, respectively. Little difference in GLUT-4 protein expression was shown in DC and DCL compared to D. GLUT-4 protein expression was decreased in DCM and increased in DCH was observed. GRP-78 protein expressions in DCL, DCM and DCH were little lower than that of D. An increase in GRP-78 protein was observed in DC. Improved insulin sensitivity with acute high intensity exercise gives the rats important therapy that lowers insulin requirement. This improvement of insulin sensitivity for glucose transport in skeletal muscle results from translocation of the GLUT-4 protein from the endoplasmic reticilum to the cell surface and increase in total quantity of GLUT-4 protein. It is not clear what mechanism reduced GRP-78 protein level in exercise group. It is merely conjectured that caffeine-induced lipolysis provided cells with energy in abundance and this relieved stress which cells are subjected to receive when performing exercise.

• Archives of Reconstructive Microsurgery
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• v.6 no.1
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• pp.29-38
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• 1997

A peripheral nerve when approximation of the ends imparts tension at the anastomosis and with a relatively long segment defect after excision of neuroma and neurofibroma cannnot be repaired by early primary suture. The one of the optimistic reconstruction method of severed peripheral nerves is to restore tension-free continuity at the repair site putting an autogenous nerve graft into the neural gap despite of ancipating motor or sensory deficit of the donor nerve area. To overcome the deficit of the autogenous nerve graft, several other conduits supplying a metabolically active environment which is able to support axon regeneration and progression, providing protection against scar invasion, and guiding the regrowing axons to the distal stump of the nerve have been studied. An author have used ipsilateral femoral vein, ipsilateral femoral vein filled with fresh thigh muscle, and autogenous sciatic nerve for the sciatic nerve defect of around 10 mm in length to observe the regeneration pattern in rat by light and electron microscopy. The results were as follows. 1. Light microscopically regeneration pattern of nerve fibers in the autogenous graft group was more abundant than vein graft and vein filled with muscle group. 2. On ultrastructural findings, the proxial end of the graft in various groups showed similar regenerating features of the axons, myelin sheaths, and Schwann cells. The fascicular arrangement of the myelinated and unmyelinated fibers was same regardless of the type of conduits. There were more or less increasing tendency in the number and the diameter of myelinated fibers correlated with the regeneration time. 3. In the middle of the graft, myelinated nerve fibers of vein filled with muscle group were more in number and myelin sheath was thinner than in the venous graft, but the number of regenerating axons in autogenous nerve graft was superior to that in both groups of the graft. The amount of collagen fibrils and amorphous materials in the endoneurial space was increased to elapsed time. 4. There was no difference in regenerating patterns of the nerve fibers of distal end of the graft. The size and shape of the myelinated nerve fbers were more different than that of proximal and middle portion of the graft. From the above results, the degree of myelination and regenerating activity in autogenous nerve is more effective and active in other types of the graft and there were no morphological differences in either ends of the graft regardless of regeneration time.

• Journal of Life Science
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• v.33 no.3
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• pp.277-286
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• 2023

Sarcopenia is the age-related loss of muscle mass and function. It is a natural part of aging and can lead to decreased mobility and increased frailty. The ubiquitin-proteasome pathway, which is involved in muscle protein degradation, is closely linked to sarcopenia. Germinated Rhynchosia nulubilis hydrolysate (GRH) has been reported to have anti-inflammatory and antioxidant properties, but there have been no reports on its inhibitory effect on muscle reduction. However, no study has yet explored the relationship between GRH and muscle loss inhibition. In this study, we evaluated the effects of GRH on muscle atrophy inhibitory activity in dexamethasone (Dexa)-induced muscle atrophy C2C12 myotubes and mouse models. Moreover, we identified a molecular pathway underlying the effects of GRH on skeletal muscle. May Grunwald-Giemsa staining showed that the length and area of myotubes increased in the groups treated with GRH. In addition, the GRH-treated group significantly reduced the expression of muscle ring finger protein 1 and muscular atrophy F-box (MAFbx) in the Dexa-induced muscular atrophy C2C12 model. GRH also improved muscle strength in C57BL/6 mice with Dexa-induced muscle atrophy, resulting in prolonged running exhaustive time and increased grip strength. We found that muscle strengthening by GRH was correlated with a decreased expression of the MAFbx gene in mouse muscle tissue. In conclusion, GRH can attenuate Dexa-induced muscle atrophy by inhibiting the ubiquitin-proteasome pathway via downregulation of the MAFbx gene expression.

• Animal cells and systems
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• v.1 no.2
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• pp.323-328
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• 1997

We have previously shown that chick muscle extracts contained at least 10 different ubiquitin C-terminal hydrolases (UCHs). In the present studies, one of the enzymes, called UCH-9, was purified by conventional chromatographic procedures using $^{125}l$-labeled ubiquitin-${\alpha}$NH-MHISPPEPESEEEEE HYC (Ub-PESTc) as a substrate. The purified enzyme behaved as a 27-kDa protein under both denaturing and nondenaturing conditions, suggesting that it consists of a single polypeptide chain. It was maximally active at pHs between 7 and 8.5, but showed little or no activity at pH below 6 and above 10. Lice other UCHs, its activity was strongly inhibited by sulfhydryl blocking reagents, such as iodoacetamide, and by Ub-aldehyde. In addition to Ub-PESTc, UCH-9 hydrolyzed Ub-aNH-protein extensions, including Ub-${\alpha}NH$-carboxyl extension protein of 80 amino acids and Ubo-${\alpha}NH$-dihydrofolate reductase. However, this enzyme was not capable of generating free Ub from mono-Ub-${\varepsilon}NH$-protein conjugates and from branched poly-Ub chains that are ligated to proteins through ${\varepsilon}NH$-isopeptide bonds. This enzyme neither could hydrolyze poly-His-tagged di-Ub. These results suggest that UCH-9 may play an important role in production of free Ub and ribosomal proteins from their conjugates.

• Archives of Plastic Surgery
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• v.34 no.6
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• pp.671-678
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• 2007

Purpose: Venous malformation(VM) which often causes pain and discomfort is the most common type of vascular malformations. Although it is presented with disfigured appearance and associated soft tissue or skeletal hypertrophy, the molecular bases of VMs are poorly understood. Differentially expressed genes(DEGs) of VMs were investigated to illuminate the molecular mechanism of the disease entity. Methods: Gene expressions of VM patients' subcutaneous tissue were studied in comparison with normal persons' by $GeneFishing^{TM}$ technique using the annealing control primers (ACPs) to identify DEGs. Candidate genes were sequenced and screened by basic local alignment search tool (BLAST) afterwards. Results: Among seventy DEGs identified, forty DEGs which had shown significantly different expression pattern were sequenced. Twenty eight out of 40 were up-regulated while 12 were down-regulated. BLAST searches revealed that 37 were known genes and 3 were unknown genes. Many genes were involved in the differentiation and remodeling of smooth muscle cells, opposed to the previous hypothesis that a lot of angiogenetic genes would be involved. Furthermore, several transcription factors and related genes, as well as cell signaling and metabolism regulators, were up regulated. Conclusion: It suggests that analysis of DEGs in VMs provide basic knowledge about its pathophysiology. and new therapeutic approaches.

• BMB Reports
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• v.40 no.6
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• pp.921-927
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• 2007

UCP2 and UCP3 are members of the uncoupling protein family, which may play roles in energy homeostasis. In order to determine the regulation of the predominant expression of UCP3 in skeletal muscle, the effects of differentiation and myogenic regulatory factors on the promoter activities of the mouse UCP2 and UCP3 genes were studied. Reporter plasmids, containing approximately 3 kb of the 5'-upstream region of the mouse UCP2 and UCP3 genes, were transfected into C2C12 myoblasts, which were then induced to differentiate. Differentiation positively induced the reporter expression about 20-fold via the UCP3 promoter, but by only 2-fold via the UCP2 promoter. C2C12 myoblasts were cotransfected with expression vectors for myogenin and/or MyoD as well as reporter constructs. The simultaneous expression of myogenin and MyoD caused an additional 20-fold increase in the reporter expression via the UCP3 promoter, but only a weak effect via the UCP2 promoter. In L6 myoblasts, only MyoD activated the UCP3 promoter, but in 3T3-L1 cells neither factor activated the UCP3 promoter, indicating that additional cofactors are required, which are present only in C2C12 myoblasts. The expression of UCP2 and UCP3 is differentially regulated during muscle differentiation due to the different responsiveness of their promoter regions to myogenin and MyoD.

• Korean Journal of Veterinary Research
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• v.20 no.1
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• pp.65-78
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• 1980

From November 1978 to April 1979, there occurred among cows many cases of abortion, premature birth, stillbirth and congenital arthrogryposis or hydranencephaly in Kyongki-do province in Korea. Epizootics recurred between February and May, 1980 in the same area. Six calves born at 8 or 10 months of gestation were examined by means of pathology and one of the calves was examined by serological test. And a survey on local occurrence of the disease in other than Kyongki-do province, was conducted. 1. At necropsy, some calves showed distinct lesions such deformities of the limbs and the vertebrae as arthrogryposis or scoliosis. Other calves revealed arthrogryposis and partial or total deficience of the cerebral hemispheres with hydranencephaly. 2. In the calves with deformities the skeletal muscle showed histologically severe hypoplasia of the muscle fibers with cellular infiltration. In the central nervous system of the calves with hydranencephaly there were minute cystic cavitation and the decrease of ventral horn cells of the spinal cord in the number. 3. Similar epizootics were also observed in the same season in the other several provinces such as Chungoheongnam-do, Kangwon-do and Jeonrabuk-do. 4. Anti-Akabane virus antibody was detected in precolostral blood from the calf with arthroglposis and hydranencephaly syndrome. 5. On these findings of the disease it was diagnosed as Akabane disease presenting the first report on the epizootics in Korea.

• CELLMED
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• v.4 no.4
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• pp.27.1-27.5
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• 2014

Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae) is a traditional Ayurvedic herb known as Kutki. It is used as a remedy for diabetes by tribes of North Eastern Himalayan region of India. Present study was conducted to explore the mechanism of antidiabetic activity of standardized aqueous extract of Picrorhiza kurroa (PkE). PkE (100 and 200 mg/kg/day) was orally administered to streptozotocin induced diabetic rats, for 14 consecutive days. Plasma insulin levels were measured and pancreas of rat was subjected to histopathological investigations. Glucose transporter type 4 (GLUT-4) protein content in the total membrane fractions of soleus muscle was estimated by Western blot analysis. Plasma insulin level was significantly increased along with concomitant increase in GLUT-4 content of total membrane fractions of soleus muscle of diabetic rats treated with extract. There was evidence of regeneration of ${\beta}$-cells of pancreatic islets of PkE treated group in histopathological examinations. PkE increased the insulin-mediated translocation of GLUT-4 from cytosol to plasma membrane or increased GLUT-4 expression, which in turn facilitated glucose uptake by skeletal muscles in diabetic rats.

• Molecules and Cells
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• v.38 no.12
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• pp.1037-1043
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• 2015

The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.375-379
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• 2003

$Ca^{2+}$ influx appears to be important for triggering myoblast fusion. It remains, however, unclear how $Ca^{2+}$ influx rises prior to myoblast fusion. Recently, several studies suggested that NMDA receptors may be involved in $Ca^{2+}$ mobilization of muscle, and that $Ca^{2+}$ influx is mediated by NMDA receptors in C2C12 myoblasts. Here, we report that other types of ionotropic glutamate receptors, non-NMDA receptors (AMPA and KA receptors), are also involved in $Ca^{2+}$ influx in myoblasts. To explore which subtypes of non-NMDA receptors are expressed in C2C12 myogenic cells, RT-PCR was performed, and the results revealed that KA receptor subunits were expressed in both myoblasts and myotubes. However, AMPA receptor was not detected in myoblasts but expressed in myotubes. Using a $Ca^{2+}$ imaging system, $Ca^{2+}$ influx mediated by these receptors was directly measured in a single myoblast cell. Intracellular $Ca^{2+}$ level was increased by KA, but not by AMPA. These results were consistent with RT-PCR data. In addition, KA-induced intracellular $Ca^{2+}$ increase was completely suppressed by treatment of nifedifine, a L-type $Ca^{2+}$ channel blocker. Furthermore, KA stimulated myoblast fusion in a dose-dependent manner. CNQX inhibited not only KA-induced myoblast fusion but also spontaneous myoblast fusion. Therefore, these results suggest that KA receptors are involved in intracellular $Ca^{2+}$ increase in myoblasts and then may play an important role in myoblast fusion.