• Title/Summary/Keyword: Protein therapy

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The Role of Actin Binding Protein -Caldesmon- of the Mechanism of $Ca^{2+}$-dependent/-independent Smooth Muscle Contraction - Approach of Basic Medical for the Study of Senile Cardiovascular Disease-related Senile Physical Therapy - (세포 내 $Ca^{2+}$-의존성/-비의존성 평활근 수축기전에 대한 액틴결합단백질-Caldesmon-의 역할 - 노인성 심혈관질환 관련 노인물리치료 연구를 위한 기초의학적 접근 -)

  • Kim, Jung-Hwan;Min, Kyung-Ok;Choi, Young-Duk;Lee, Joon-Hee;Chon, Ki-Young
    • Journal of Korean Physical Therapy Science
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    • v.11 no.1
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    • pp.20-27
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    • 2004
  • It is widely accepted that smooth muscle contraction is triggered by intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) released from intracellular $Ca^{2+}$ stores such as sarcoplasmic reticulum (SR) and from the extracellular space, The increased $[Ca^{2+}]_i$ can phosphorylate the 20-kDa myosin light chain ($MLC_{20}$) by activating MLC kinase (MLCK), and this initiates smooth muscle contraction. In addition to the $[Ca^{2+}]_i$-MLCK-tension pathway, a number of intracellular signal molecules, including mitogen-activated protein kinase (MAPK), protein kinase C (PKC), phosphatidylinositol 3-kinase (PI3K), and Rho-associated coiled coil-forming protein kinase (ROCK), play important roles in the regulation of smooth muscle contraction. However, the mechanisms regulating contraction of caldesmon (CaD), actin-binding protein, are not entirely elucidated in the presence of $Ca^{2+}$. It is known that CaD tightly interacts with actin and inhibits actomyosin ATPase activity. Therefore, the purpose of the present study was to investigate the roles of $Ca^{2+}$-dependent CaD in smooth muscle contraction. Endothelin-1 (ET-1), G-protein coupled receptor agonist and vasoconstrictor, increased both vascular smooth contraction and phosphorylation of CaD in the presence of $Ca^{2+}$. These results suggest that ET-1 induces contraction and phosphorylation of CaD in rat aortic smooth muscle, which may he mediated by the increase of $[Ca^{2+}]_i$.

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The Activity of Protein Kinases on the Endothelin-1-induced Muscle Contraction and the relationship of Physical Therapy (Endothelin-1-유도 근수축에 관여하는 부활효소의 활성과 물리치료의 상관성)

  • Kim, Mi-Sun;Kim, Il-Hyun;Hwang, Byong-Yong;Kim, Jung-Hwan
    • The Journal of Korean Physical Therapy
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    • v.20 no.3
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    • pp.53-59
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    • 2008
  • Purpose: The non-receptor-type protein tyrosine kinase Syk (636 amino acids, 72 kDa) is ubiquitously expressed in hematopoietic stem cells and has been widely studied as a regulator and effector of B cell receptor signaling that occurs in processes such as differentiation, proliferation and apoptosis. However, the mechanism relating Syk and p38 mitogen-activated protein kinases (p38MAPK) by endothelin-1 (ET-1, 21 amino acids) stimulation in muscle cells, especially in the volume-dependent hypertensive state, remains unclear. Methods: In this study, we investigated the relationship between Syk and p38MAPK for isometric contraction and enzymatic activity by ET-1 from rat aortic smooth muscle cells and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive state rats (ADHR). Results: The systolic blood pressure was significantly increased in ADHR than in a control group of animals. ET-1 induced isometric contraction and phosphorylation of p38MAPK, which was increased in muscle strips from ADHR. Increased vasoconstriction and phosphorylation of p38MAPK induced by treatment with 30 nM ET-1 were inhibited by the use of 10${\mu}M$ SB203580, an inhibitor of p38MAPK from ADHR. Furthermore, ET-1 induced isometric contraction and phosphorylation of Syk and p38MAPK, which were increased in the aortic smooth muscle cells. Increased tension and phosphorylation of Syk and p38MAPK induced by ET-1 were inhibited by SB203580 from rat aortic smooth muscle cells. Conclusion: These results, suggest that the Syk activity affects ET-1-induced contraction through p38MAPK in smooth muscle cells and that the same pathway directly or indirectly is associated with volume dependent hypertension. The findings suggest the need to develop cardiovascular disease-specialized physical therapy.

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The Activation of Stress-induced Heat Shock Protein 27 and the Relationship of Physical Therapy (스트레스-유도 열충격단백질 27(Heat Shock Protein 27)의 활성과 물리치료의 상관성)

  • Kim, Mi-Sun;Lee, Sung-Ho;Kim, Il-Hyun;Hwang, Byong-Yong;Kim, Jung-Hwan
    • The Journal of Korean Physical Therapy
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    • v.20 no.1
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    • pp.57-65
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    • 2008
  • Purpose: Heat shock proteins (HSPs) are a group of proteins that are activated when cells are exposed to a variety of environmental stresses, such as infection, inflammation, exposure to toxins, starvation, hypoxia, brain injury, or water deprivation. The activation of HSPs by environmental stress plays a key role in signal transduction, including cytoprotection, molecular chaperone, anti-apoptotic effect, and anti-aging effects. However, the precise mechanism for the action of small HSPs, such as HSP27 and mitogen-activated protein kinases (MAPKs: extracellular-regulated protein kinase 1/2 (ERK1/2), p38MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), is not completely understood, particularly in application of cell stimulators including platelet-derived growth factor (PDGF), angiotensin II (AngII), tumor necrosis factor $\alpha$ (TNF$\alpha$), and $H_2O_2$. This study examined the relationship between stimulators-induced enzymatic activity of HSP27 and MAPKs from rat smooth and skeletal muscles. Methods: 2-dimensional electrophoresis (2DE) and matrix assisted laser desorption ionizationtime-of-flight/time-of-flight (MALDI-TOF/TOF) analysis were used to identify HSP27 from the intact vascular smooth and skeletal muscles. Three isoforms of HSP27 were detected on silver-stained gels of the whole protein extracts from the rat aortic smooth and skeletal muscle strips. Results: The expression of PDGF, AngII, TNF$\alpha$, and $H_2O_2$-induced activation of HSP27, p38MAPK, ERK1/2, and SAPK/JNK was higher in the smooth muscle cells than the control. SB203580 (30${\mu}$M), a p38MAPK inhibitor, increased the level of HSP27 phosphorylation induced by stimulators in smooth muscle cells. Furthermore, the age-related and starvation-induced activation of HSP27 was higher in skeletal muscle cells (L6 myoblast cell lines) and muscle strips than the control. Conclusion: These results suggest, in part, that the activity of HSP27 and MAPKs affect stressors, such as PDGF, AngII, TNF$\alpha$, $H_2O_2$, and starvation in rat smooth and skeletal muscles. However, more systemic research will be needed into physical therapy, including thermotherapy, electrotherapy, radiotherapy and others.

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A Review on Thirst Disease Prescription in "Sikryochanyo" ("식료찬요(食療纂要)"에 나타난 소갈(消渴)의 식치(食治)에 대(對)한 소고(小考))

  • Song, Ji-Chung;Kim, Sang-Un;Chae, Song-A;Eom, Dong-Myung
    • Journal of Korean Medical classics
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    • v.25 no.3
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    • pp.39-49
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    • 2012
  • Objective : "Sikryochanyo"written by Jeon Soonyi is the first Food-Therapy book at Korea. In "Sikryochanyo", there are many kinds of food-Therapy including prescriptions for thirst disease. Conception of hirst disease in traditional mendicine contains diabetes in some aspects. One of the Ingeative methods in diabetes limits taking protein but "Sikryochanyo" shows several prescriptions including protein. Method : We will try to find out cases of Food-therapy for thirst disease in "Sikryochanyo" and classify several prescriptions including protein. Result : In "Sikryochanyo", several prescriptions for thirst disease including protein were treated as materia medica widely such as stomach of cow and pig, intestine of pig, head of dear, rabbit, chicken, goose, pheasant, milk and lung of sheep. Conclusion : On several types of prescriptions for thirst disease including protein there are plenty of usage with its own effectiveness.

Review of the muscle plasticity (근육의 가소성에 대한 고찰)

  • Baek Su-Jeong;Kim Dong-Hyun;Kim Jin-Sang
    • The Journal of Korean Physical Therapy
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    • v.15 no.2
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    • pp.100-110
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    • 2003
  • The purpose of this article is to understand of the muscle adaptation based on myosin heavy chain. Especially, skeletal muscle dadptation in related to aging, unloading, training will discussed. MHC expression is highly plastic in muscles of adult mammals in accordance with the environmental conditions. These changes is called muscle plasticity. The plasticity is the atility of muscle cell to alter either the quantity of protein or the type of protein. MHC is both an important structural and regulatory protein comprising the contractile apparatus.

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The Activity of Hypertension-related Protein Kinase C and the Relationship of Physical Therapy (고혈압-연관 단백질 부활효소 C의 활성과 물리치료의 상관성)

  • Kim, Jung-Hwan
    • The Journal of Korean Physical Therapy
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    • v.20 no.3
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    • pp.61-68
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    • 2008
  • Purpose: Protein kinase C (PKC) is a member of a family of serine/threonine kinases that are activated by diacylglycerol (DG) and PKC stimulants. PKC play a key role in signal transduction, including muscle contraction, cell migration, apoptosis, cell proliferation and differentiation. However, the mechanism relating mitogen-activated protein kinases (MAPKs) and PKC, especially in the volume-dependent hypertensive state, remains unclear. Methods: In the present study, I investigated the relationship between PKC and MAPKs for isometric contraction, PKC translocation, and enzymatic activity from normotensive sham-operated rats (NSR) and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive rats (ADHR). Results: Systolic blood pressure was significantly increased in ADHR than in NSR. Physiological salt solution (PSS)-induced resting tension and the intracellular $Ca^{2+}$ concentration ([$Ca^{2+}{_i}$]) were different in the ADHR and NSR. The expression of PKC$\alpha$, PKC$\beta$II, PKC$\delta$, PKC$\varepsilon$ and PKC$\xi$ were different between the cytoplasmic and membranous fractions. However, expression of the PKC isoforms did not differ for the ADHR and NSR. The use of 12-deoxyphorbol 13-isobutyrate (DPB, a PKC stimulant) induced isometric contraction in $Ca^{2+}$-free medium, which was diminished in muscle strips from ADHR as compared to NSR. Increased vasoconstriction and phosphorylation induced by the use of 1 ${\mu}$M DPB were inhibited by treatment with 10 ${\mu}$M PD098059 and 10 ${\mu}$M SB203580, inhibitors of extracellular-regulated protein kinase 1/2 (ERK1/2) and p38 MAPK from ADHR, respectively. Conclusion: These results suggest that the development of aldosterone analogue-induced hypertension is associated with an altered blood pressure, resting tension, [$Ca^{2+}{_i}$], and that the $Ca^{2+}$-independent contraction evoked by PKC stimulants is due to the activation of ERK1/2 and p38 MAPK in volume-dependent hypertension. Therefore, it is suggested that PKC activity affects volume-dependent hypertension and the need to develop cardiovascular disease-specialized physical therapy.

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Effects of Hominis Placenta Pharmacopuncture and Electroacupuncture Neuroprotection in Contused Spinal Cord of Rats (척수손상 흰쥐에서 자하거 약침과 침전기 자극이 신경성장인자 발현에 미치는 영향)

  • Kim, Eun-Jung;Kim, Gye-Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.2
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    • pp.257-263
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    • 2011
  • This study was designed to investigate the effects of Hominis placenta pharmacopuncture treatment and electroacupuncture therapy on the functional recovery and histological change, protein expression in spinal cord injury(SCI) rats. Experimental groups were divided into the Group I(normal control rat), Group II(Non-treatment after spinal cord injury induction), Group III(Hominis placenta pharmacopuncture treatment after SCI induction), Group IV (Electroacupuncture therapy after SCI induction), Group V(Hominis placenta pharmacopuncture treatment and electroacupuncture therapy after SCI induction). After operation, rats were tested at modified Tarlov test at 1 to 3 days with divided into 4 groups, and motor behavior test(BBB locomotor rating scale, Grid walk test) was examined at 3, 7, 14, and 21 days. For the observation of damage change and size of the organized surface in muscle and spinal cord, histopathological studies were performed at 21 days by H & E stain, and BDNF & NT-3 protein expression studies were performed at 21 days. Acco rding to the results, Hominis placenta pharmacopuncture treatment and electroacupuncture therapy can play a role in facilitating recovery of locomotion following spinal cord injury. Specially, Hominis placenta pharmacopuncture treatment and electroacupuncture combimed therapy after SCI induction was most improvement in functional recovery, BDNF, and NT-3 protein synthesis.

Future Cancer Therapy with Molecularly Targeted Therapeutics: Challenges and Strategies

  • Kim, Mi-Sook
    • Biomolecules & Therapeutics
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    • v.19 no.4
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    • pp.371-389
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    • 2011
  • A new strategy for cancer therapy has emerged during the past decade based on molecular targets that are less likely to be essential in all cells in the body, therefore confer a wider therapeutic window than traditional cytotoxic drugs which mechanism of action is to inhibit essential cellular functions. Exceptional heterogeneity and adaptability of cancer impose significant challenges in oncology drug discovery, and the concept of complex tumor biology has led the framework of developing many anticancer therapeutics. Protein kinases are the most pursued targets in oncology drug discovery. To date, 12 small molecule kinase inhibitors have been approved by US Food and Drug Administration, and many more are in clinical development. With demonstrated clinical efficacy of bortezomib, ubiquitin proteasome and ubiquitin-like protein conjugation systems are also emerging as new therapeutic targets in cancer therapy. In this review, strategies of targeted cancer therapies with inhibitors of kinases and proteasome systems are discussed. Combinational cancer therapy to overcome drug resistance and to achieve greater treatment benefit through the additive or synergistic effects of each individual agent is also discussed. Finally, the opportunities in the future cancer therapy with molecularly targeted anticancer therapeutics are addressed.

Endogenous Gene Expression of p53 and Regulatory Subunits of Cyclic AMP-dependent Protein Kinase in Ovarian Cancer Cells (난소암 세포주에서 p53과 Cyclic AMP-dependent Protein Kinase의 Regulatory Subunit 유전자들의 발현에 관한 연구)

  • Jin Seo;Park, Woonmee;Hwang, Eun-Seong;Lee, Je-Ho;Hong, Seung-Hwan
    • The Korean Journal of Zoology
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    • v.38 no.2
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    • pp.204-211
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    • 1995
  • In an effort to develop a new therapeutic strategy for human gene therapy of solid ovarian tumor, we studied the expression of the p53 tumor suppressor Sene as well as regulatory subunits of cyclic AMP (cAMP)-dependent protein kinase in human ovarian carcinoma cells. Four cell lines (2774, Caov-3, SK-OV-3 and OVCAR-3) were selected for the analyses. The p53 transcript and protein were detected only in the 2774 cell line by Northern and Western Bnalysis. In the relatively fast growing cell line, SK-OV-3, the %rope 1 a regulstorv subunit (RIA of CAMP-dependent protein kinase was the highest among the four cell lines. The expression level of $RII\beta$ protein was low in the four cell lines examined. These results maw point to a direction to select the target gene(sl to be employed for gene therapy to control the ovarian cancer.

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The Effect of Aquatic-Exercise on Skeletal Muscle Weight and Myofibrillar Protein Content of Rats with Steroids Injection (수중운동이 스테로이드를 투여한 흰쥐의 골격근 무게 및 단백질 함량에 미치는 효과)

  • Yoon Se-Won;Kim Tae-Youl;Choi Suk-Joo
    • The Journal of Korean Physical Therapy
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    • v.15 no.3
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    • pp.189-201
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    • 2003
  • The purpose of this study was to know the effect of aquatic-exercise on muscle atrophy which induced by steroid injection. The forty-eight Sparague-Dawley adult male rats were assigned to the 4 groups; Group I (distilled water injection), Group II (steroid injection), Group III (distilled water injection with aquatic exercise), Group IV (steroid injection with aquatic exercise). We observed their body weight, muscle relative weight, myofibrillar protein content. The results of this study were as follows; 1. Body weight was decreased rapidly on steroid injection groups in comparison with distilled water injection groups after 2 weeks (p<0.01), but that was almost recovered as before test on steroid injection group with aquatic exercise. 2. The relative weight of gastrocnemius muscles was decreased on steroid injection groups in comparison with distilled water injection groups. however, Decrease of it on steroid injection group with aquatic exercise for steroid injection group was fallen. There was very significant difference after 4 weeks (p<0.01). 3. Myofibrillar protein content of gastrocnemius muscles was decreased on steroid injection groups in comparison with distilled water injection groups. however, Decrease of it on steroid injection group with aquatic exercise for steroid injection group was fallen. There was significant difference after 4 weeks (p<0.05).

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