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ABSTRACT: OBJECTIVE: Velocity-vector imaging (VVI) represents a valuable new method for noninvasive quantification of vascular properties associated with aging. The purpose of this study was to assess the correlations between VVI parameters and histological changes with aging.Approach and Results-Fourteen mongrel dogs were classified as either young (n=7; age, 1-2 years; female; weighing 22-29 kg) or senescent (n=7; age, 8-12 years; female; weighing 36-45 kg). The short-axis image of the descending thoracic aorta was obtained for VVI analysis with transesophageal echocardiography. The location of the image was identified using fluoroscopic guidance, and the aortic tissue was extracted. After dividing the aortic wall into 6 segments, both regional and segmental tissue collagen and elastin contents were quantified and correlated with the aortic elastic properties. In the regional analysis, the M-mode-derived aortic dimensions and elastic moduli except for intima-media thickness were not significantly different between the groups, whereas the VVI-derived aortic area and fractional area changes showed more dilated and stiffer aorta in senescent dogs. Also, fractional area change was significantly correlated with the tissue collagen content unlike the M-mode-derived elastic moduli. In the segmental analysis, the radial velocity, circumferential strain, and strain rates of VVI were more reduced in senescent dogs than young dogs, and the radial velocity and circumferential strain showed independent associations with the collagen content of the corresponding aortic wall. CONCLUSIONS: VVI was a feasible method for direct quantification of aortic elastic properties with a significant histological correlation.
Arteriosclerosis Thrombosis and Vascular Biology 04/2013; · 6.37 Impact Factor
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ABSTRACT: According to the cytokine hypothesis of depression, cytokines play key roles in the behavioral, neuroendocrinal, and neurochemical
features of depression. In this study, we used a bioplex assay to simultaneously measure the levels of 23 plasma cytokines
in 18 patients with late-life depression and 38 normal controls, and these levels were compared between the two groups. The
plasma interleukin-1alpha (IL-1α) levels were found to be significantly different between the two groups. After adjusting
for age, gender, low-density lipoprotein cholesterol, and triglyceride, the plasma IL-1α levels were significantly higher
in the patients with late-life depression than in the normal control subjects. Thus, this study provides preliminary evidence
that plasma IL-1α may play important roles in the pathogenesis of late-life depression.
Neurological Sciences 04/2012; 30(5):435-438. · 1.32 Impact Factor
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ABSTRACT: Saturated fatty acids are known to activate macrophages and induce vascular inflammation. Although cytokines from activated macrophage influence other vascular cells, the influence of saturated fatty acids on the paracrine effect of macrophages is not fully understood yet. Here we examined the impact of palmitate on the effect of macrophages on vascular smooth muscle cells (SMCs) and their mediators. SMCs proliferation increased significantly after treatment with conditioned media from palmitate-stimulated RAW264.7 cells. SMC migration was found to be greater after treatment with palmitate-conditioned media. SM α-actin and SM22α were decreased in SMCs treated with palmitate-conditioned media. When stimulated with palmitate, RAW264.7 cells secreted more bone morphogenetic protein (BMP)2 and BMP4 into the cell culture media. SMC proliferation, migration, and phenotypic changes were attenuated after treatment of neutralizing antibodies against BMPs or knockdown of BMPs with siRNA. The influences of these proteins were further confirmed by direct treatment of recombinant BMP2 and BMP4 on SMCs. Particularly, the effects of BMPs on SMC migration on phenotypic change were obvious, whereas their effect on SMC proliferation seemed not significant or modest. In conclusion, palmitate promoted macrophages' paracrine effects on SMC proliferation, migration, and phenotypic change. The effect of stimulated macrophages was mediated, at least in part, by BMP2 and BMP4. These results suggest a novel mechanism linking saturated fatty acids and the progression of vascular diseases that is possibly mediated by BMPs from macrophages.
PLoS ONE 01/2012; 7(2):e29100. · 4.09 Impact Factor
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ABSTRACT: Transcriptional factor nuclear factor-kappaB (NF-κB) plays a crucial role in human breast cancer cell invasion and metastasis. The carboxyl terminus of Hsc70-interacting protein (CHIP) is a U-box-type ubiquitin ligase that induces ubiquitination and proteasomal degradation of its substrate proteins. In this study, we investigated the role of CHIP in the NF-κB pathway in the invasion of MDA-MB-231 cells, a highly aggressive breast cancer cell line. We showed that overexpression of CHIP significantly inhibits the invasion of the MDA-MB-231 cells. The overexpression of CHIP suppressed expression of urokinase plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in MDA-MB-231 cells. Moreover, CHIP strongly inhibited the nuclear localization and the transcriptional activity of NF-κB. The activation of the IkappaB kinase complex (IKK) was also blocked by CHIP overexpression. Importantly, CHIP overexpression resulted in a significant decrease in the level of TNF receptor-associated factor 2 (TRAF2), an upstream key player in the NF-κB pathway. However, the level of TRAF2 was restored after treatment with a proteasome inhibitor, MG-132. Moreover, CHIP overexpression promoted the ubiquitination of TRAF2. We also found cell invasion significantly decreased in cells transfected with TRAF2 small interfering RNA (siRNA). In contrast, when CHIP expression was suppressed by siRNA in poorly invasive MCF-7 cells, cell invasion significantly increased in conjunction with enhanced NF-κB activation and TRAF2 levels. Taken together, these results suggest that CHIP regulates NF-κB-mediated cell invasion via the down-regulation of TRAF2.
Journal of Cellular Biochemistry 07/2011; 112(12):3612-20. · 2.87 Impact Factor
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ABSTRACT: C-reactive protein (CRP) is one of the most important biomarker for cardiovascular diseases. Recent studies have shown that CRP affects cell survival, differentiation and apoptosis. However, the effect of CRP on the cell cycle has not been studied yet. We investigated the cell cycle alterations and cellular mechanisms induced by CRP in H9c2 cardiac myocytes. Flow cytometry analysis showed that CRP-treated H9c2 cells displayed cell cycle arrest in G0/G1 phase. CRP treatment resulted in a significant reduction in the levels of CDK4, CDK6 and cyclin D1 in a concentration-dependent manner. Interestingly, CRP caused an increase in the p53 accumulation and its phosphorylation on Ser15, leading to induce p21 upregulation. Treatment with a specific p53 inhibitor, PFT-α restored the levels of CDK4 and CDK6. A significant increase of ERK1/2 phosphorylation level was detected in CRP-treated cells. Furthermore, pretreatment of a specific ERK inhibitor resulted in decreased p53 phosphorylation and p21 induction. ERK inhibitor pretreatment induced significant restoration of protein levels of CDK4 and CDK6, leading to re-entry into the cell cycle. In addition, increased phosphorylation of p53 and ERK induced by CRP was considerably reversed by Fc gamma receptor IIIa (FcγRIIIa) knock-down using siRNA. FcγRIIIa siRNA transfection also restored the levels of cell cycle proteins. Our study has provided the first proposal on the novel insights into how CRP directly affects cell cycle in cells.
Biochemical and Biophysical Research Communications 06/2011; 410(3):525-30. · 2.48 Impact Factor
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ABSTRACT: Cell-penetrating peptides (CPPs), including TAT-CPP, have been used to deliver exogenous proteins into living cells. Although a number of proteins fused to TAT-CPP can be delivered into various cells, little is known about the proteolytic cleavage of TAT-fusion proteins in cells. In this study, we demonstrate that a small heat shock protein (sHSP), alphaB-crystallin (αB-crystallin), delivered by TAT-CPP is susceptible to proteolytic cleavage by matrix metalloproteinase-1 (MMP-1) in cardiac myoblast H9c2 cells. Recombinant TAT-αB-crystallin was efficiently transduced into H9c2 cells. For a few hours following protein transduction, generation of a 14-kDa fragment, a cleavage band of TAT-αB-crystallin, increased in a time-dependent manner. This fragment was observed only in detergent-insoluble fractions. Interestingly, treatment with MMP inhibitors blocked the cleavage of TAT-αB-crystallin. In test tubes, recombinant MMP-1 processed TAT-αB-crystallin to generate the major cleavage fragment 14-kDa, as observed in the cells treated with TAT-αB-crystallin. The N-terminal sequences of the 14-kDa fragment were identified as Leu-Arg-Ala-Pro-Ser-Trp-Phe, indicating that this fragment is generated by cleavage at Phe54-Leu55 of αB-crystallin. The MMP-1-selective inhibitor abolished the production of 14-kDa fragments in cells. In addition, the cleaved fragment of TAT-αB-crystallin was significantly reduced in cells transfected with MMP-1 siRNA. Moreover, the enzymatic activity of MMP-1 was markedly increased in TAT-αB-crystallin-treated cells. TAT-αB-crystallin has a cytoprotective effect on H9c2 cells under hypoxic insult, moreover, MMP-1-selective inhibitor treatment led to even increased cell viability. These results suggest that MMP-1 is responsible for proteolytic cleavage of TAT-αB-crystallin during its intracellular transduction in H9c2 cells.
Journal of Cellular Biochemistry 05/2011; 112(9):2454-62. · 2.87 Impact Factor
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ABSTRACT: Gene transfer of basic fibroblast growth factor (bFGF) has been shown to induce significant endothelial migration and angiogenesis in ischemic disease models. Here, we investigate what factors are secreted from skeletal muscle cells (SkMCs) transfected with bFGF gene and whether they participate in endothelial cell migration. We constructed replication-defective adenovirus vectors containing the human bFGF gene (Ad/bFGF) or a control LacZ gene (Ad/LacZ) and obtained conditioned media, bFGF-CM and LacZ-CM, from SkMCs infected by Ad/bFGF or Ad/LacZ, respectively. Cell migration significantly increased in HUVECs incubated with bFGF-CM compared to cells incubated with LacZ-CM. Interestingly, HUVEC migration in response to bFGF-CM was only partially blocked by the addition of bFGF-neutralizing antibody, suggesting that bFGF-CM contains other factors that stimulate endothelial cell migration. Several proteins, matrix metalloproteinase-1 (MMP-1), plasminogen activator inhibitor-1 (PAI-1), and cathepsin L, increased in bFGF-CM compared to LacZ-CM; based on 1-dimensional gel electrophoresis and mass spectrometry. Their increased mRNA and protein levels were confirmed by RT-PCR and immunoblot analysis. The recombinant human bFGF protein induced MMP-1, PAI-1, and cathepsin L expression in SkMCs. Endothelial cell migration was reduced in groups treated with bFGF-CM containing neutralizing antibodies against MMP-1 or PAI-1. In particular, HUVECs treated with bFGF-CM containing cell-impermeable cathepsin L inhibitor showed the most significant decrease in cell migration. Cathepsin L protein directly promotes endothelial cell migration through the JNK pathway. These results indicate that cathepsin L released from SkMCs transfected with the bFGF gene can promote endothelial cell migration.
Experimental and Molecular Medicine 02/2011; 43(4):179-88. · 2.48 Impact Factor
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ABSTRACT: Heat shock protein 90 (HSP90), one of the most abundant proteins in the cardiac cells is essential for cell survival. Previous studies have shown that angiotensin II induces cardiac cell hypertrophy. However, the role of HSP90 in the angiotensin II-induced cardiac hypertrophy is unclear. In this study, we showed that HSP90 regulated angiotensin II-induced hypertrophy via maintenance of the IκB kinase (IKK) complex stability in cardiac cells. An HSP90 inhibitor, geldanamycin (GA), significantly suppressed angiotensin II-induced [³H]leucine incorporation and atrial natriuretic factor expression in cardiac cells. GA also inhibited the NF-κB activation induced by angiotensin II. Importantly, treatment with GA caused a degradation of IKKα/β; on the other hand, a proteasome-specific inhibitor restored the level of IKKα/β. We also found that GA prevented HSP90-IKKs complex induced by angiotensin II in cardiac cells. The small interfering RNA (siRNA)-mediated knockdown of HSP90 expression significantly inhibited angiotensin II-induced cell hypertrophy and NF-κB activation. These results suggest that angiotensin II-induced cardiac hypertrophy requires HSP90 that regulates the stability and complex of IKK.
Experimental and Molecular Medicine 10/2010; 42(10):703-11. · 2.48 Impact Factor
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ABSTRACT: It has been suggested that the metabolic syndrome (MetS) is associated with increased risk for heart failure (HF) and progression of HF. However, the underlying mechanisms are unclear. We tested whether the presence of the MetS would be associated with the increased degree of inflammatory state in HF.
Ninety-one eligible consecutive stable HF patients participated in this cross-sectional study. Anthropometric measurements were carried out and serum concentrations of lipoproteins, apolipoproteins (apoB, apoAI) and high sensitivity C-reactive protein (hsCRP) were measured. The simultaneous measurement of 17 cytokines using bioplex analysis was used.
Thirty-five subjects (39% of total, 48% of males and 31% of females) were classified as having the MetS in total HF patients. Serum concentrations of apoB (p<0.005) were significantly higher and the ratio of apoAI and apoB was significantly lower (p<0.01) in HF patients with MetS than those without MetS. Plasma levels of IL-8 (p<0.05) were significantly higher in HF patients with MetS than those without MetS. In addition, serum concentrations of hsCRP (p<0.005) were significantly higher in HF patients with MetS compared to those without MetS.
The MetS in HF is associated with increased degree of inflammation, which provides information regarding the relationship between inflammation and HF with MetS.
Clinica chimica acta; international journal of clinical chemistry 06/2009; 405(1-2):139-42. · 2.54 Impact Factor
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ABSTRACT: A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (beta-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and beta-NGF may be useful in differentiating subtypes of MCI.
Cellular & molecular immunology 05/2009; 6(2):143-7. · 2.99 Impact Factor
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ABSTRACT: Inflammatory mechanisms within the central nervous system contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Sixty-nine subjects were consecutively recruited from October 2005 to February 2007. Fifteen individuals were excluded from the study and we ultimately enrolled 19 not cognitively impaired subjects, 25 mild cognitive impairment patients, and 10 Alzheimer's disease patients. To examine the inflammatory markers of mild cognitive impairment and Alzheimer's disease, we measured the plasma concentrations of 23 cytokines using a bioplex assay. The results showed that the macrophage migration inhibitory factor was higher in mild cognitive impairment and in Alzheimer's disease patients compared with the not cognitively impaired group; the results also showed that monokine induced by gamma interferon was higher in Alzheimer's disease patients than in not cognitively impaired subjects, as well as those of the mild cognitive impairment group [corrected].
Immunology letters 11/2008; 121(2):105-9. · 2.91 Impact Factor
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ABSTRACT: Heat shock protein 27 (HSP27) is an intracellular stress protein with the cytoprotective effect for a variety of noxious stresses. In this study, using a protein delivery system, we demonstrated the potential cytoprotective effect of HSP27 as a therapeutic protein in cardiac cells and ischemia/reperfusion animal model. We constructed a recombinant HSP27 fused to the protein transduction domain (PTD) derived from HIV-1 TAT protein. Purified recombinant TAT-HSP27 protein was efficiently delivered to H9c2 cells, and its transduction showed cytoprotective effect against the hypoxic stress. Moreover, transduction of TAT-HSP27 also attenuated hypoxia-induced apoptosis, which was accompanied by reduced caspase-3 activity. In addition, intraperitoneal injection of TAT-HSP27 into rat resulted in efficient protein transduction in heart tissues, decreased infarcted myocardium (control vs TAT-HSP27, 39.1% vs 29.5%, P<0.05) and preserved heart function (fractional shortening, 15.6% vs 33.4%, P<0.05), as determined at 7 d after I/R. These results suggest that the PTD-mediated delivery of HSP27 protein may represent a potential therapeutic strategy as protein drug for ischemic heart diseases.
Biochemical and Biophysical Research Communications 11/2007; 363(2):399-404. · 2.48 Impact Factor
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Kyung Hye Lee
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ABSTRACT: There is a decrease in the number of new midwives, resulting from the shutdown of midwifery education program in hospitals due to a decrease in birthrate in the Republic of Korea. To solve this problem, the current medical laws on midwifery education system in Korea should be revised; nurse-midwifery specialist programs must be established in educational institutes with nursing programs. To support this argument, the midwifery education programs of America, Europe, Australia, and Japan have been discussed, and a nurse-midwifery specialist curriculum at the master's level, based on the nurse-practitioner system of Korea, has been suggested. Since this assertion is very important and urgent for solving the future population problem of Korea and providing health care for women and children, it should be realized into action immediately.
Journal of Educational Evaluation for Health Professions 02/2006; 3:5.
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ABSTRACT: Lysophosphatidylcholine (lysoPC) induces vascular smooth muscle cell (VSMC) proliferation and migration, which has been proposed to initiate the intimal thickening in coronary atherosclerotic lesions. Berberine is an alkaloid in Berberis aquifolium and many other plants. Recently, it has been shown to have beneficial effects on the cardiovascular system, such as anti-hyperglycemic and cholesterol-lowering activity. In this study, we investigated its effects on lysoPC-induced VSMC proliferation and migration. Berberine inhibited lysoPC-induced DNA synthesis and cell proliferation in VSMCs, as well as migration of the lysoPC-stimulated VSMCs. It also inhibited the activation of extracellular signal-regulated kinases (ERKs) and reduced transcription factor AP-1 activity and the lysoPC-induced increases in intracellular reactive oxygen species (ROS). These results indicate that the inhibitory effects of berberine on lysoPC-stimulated VSMC proliferation and migration are attributable to inhibition of ROS generation and hence of activation of the ERK1/2 pathway. This suggests that berberine has potential in the prevention of atherosclerosis and restenosis.
Molecules and Cells 01/2006; 20(3):429-34. · 2.18 Impact Factor
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Kyung-Hye Lee,
SoYeon Lim,
Seok-Min Kang,
Dae Hyeok Kim,
Hong Keun Cho,
Ji Hyung Chung,
Hyuck Moon Kwon,
kwang-Hoe Chung,
Hakbae Lee,
Yangsoo Jang,
Ki-Chul Hwang
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ABSTRACT: Reactive oxygen species-mediated cellular injury is involved in the pathogenesis of many diseases, including those affecting the cardiovascular system, such as myocardial ischemia-reperfusion injury, inflammation, and atheroscleosis. Raxofelast (IRFI-016; (+/-)-5-acetoxy-2, 3-dihydro-4, 6, 7-trimethyl-2-benzofuran-acetic acid) was designed with the aim of maximizing the antioxidant potency of phenols chemically related to vitamin E. The antioxidant activity of raxofelast has been convincingly demonstrated in several in vitro studies and in various models of ischemia-reperfusion injury. In this study, the antiproliferative effects of raxofelast were investigated to determine whether transduction signals and protooncogenes are affected in H(2)O(2)-stimulated rat aortic smooth muscle cells. In a tetrazolium-based colorimetric assay, the proliferation of rat aortic smooth muscle cells was increased by 3-fold in 0.1% fetal bovine serum/Dulbecco's modified Eagle's medium (DMEM) containing 500 microM H(2)O(2), indicating that exogenous 500 microM H(2)O(2) was a growth stimulator of rat aortic smooth muscle cells. Exogenous H(2)O(2) significantly activated extracellular signal-regulated kinases (ERKs) activity within 30 min and raxofelast inhibited the ERKs activation dose dependently in 500 microM H(2)O(2)-stimulated rat aortic smooth muscle cells (IC(50): 200 microM). Raxofelast reduced the intracellular reactive oxygen species generated by exogenous H(2)O(2) in a dose-dependent manner. In 500 microM H(2)O(2)-stimulated rat aortic smooth muscle cells, raxofelast dramatically attenuated the activation of mitogen-activating protein kinase (MAPK)/ERK kinase 1, 2 (MEK1,2) and protein kinase C (PKC) without affecting Ras expression. Induction of c-myc mRNA was significantly reduced dose dependently up to 100 microM by raxofelast in concentrations. These data indicate that the antiproliferative effects of raxofelast in H(2)O(2)-stimulated rat aortic smooth muscle cells may involve the suppression of intracellular reactive oxygen species formation and the inhibition of ERKs by inactivation through PKC and MEK1,2 and down-regulation of c-myc expression, regardless of Ras activation.
European Journal of Pharmacology 02/2004; 484(2-3):119-25. · 2.52 Impact Factor
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Kyung Hye Lee
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ABSTRACT: A midwife is a medical professional who has a nursing license, and is also licensed as a midwife with one additional year of education. In this globalization era, a midwife's role is increasing in importance for women and children's health care worldwide.
The primary purpose was to analyze midwifery education programs in Korea and other nations. The secondary purpose was to define strategies to improve midwifery education and practice, and to extend the role of a midwife women and children's health care in Korea.
1) The definition of a midwife and midwifery practice recognized internationally by World Health Organization (WHO) and International Council of Nurse Midwives (ICNM) was identified. 2) Midwifery education programs of Korea, U.S.A., Sweden, Australia, and Japan, were investigated and discussed. 3) Core competencies for the basic midwifery practice suggested by ACNM of the U.S.A. were reviewed as standard of midwifery practice. 4) As for the midwifery education system, a Masters degree program in a college of nursing is suggested. 5) The role of a midwife includes not only health care of childbirth women and newborn babies, but also a lifelong health care of women as well as her family and children.
An effort to extend the midwife's role and to improve service is imperative. The Laws/Acts related to midwives should be revised in regard to education, and practices, and the national examination for midwifery licensure needs revision to qualify for international approval. Also, midwifery curriculum and standards of practice need to be evaluated periodically, and an effective system needs to be established to renew midwife licenses.
Taehan Kanho Hakhoe chi 12/2003; 33(8):1111-8.
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ABSTRACT: The purposes of this study is to develop an educational program to prevent sexual abuse of children and to improve the physical and mental health of children by providing a rape-free environment and safety education. This program will provide parents and children with information on how to prevent sexual abuse in children. Children learn specific methods to avoid being victimized both at home and outside the home through a learning game and simulation, which is based on problem solving.
This program was developed based on a literature reviews, surveys and negotiation process. School- aged-children, parents, and teachers were interviewed to reveal their educational needs based on their experiences related to sexual abuse.
This program includes useful subjects such as safety education, early detection of sexual abuse, crisis management, resource persons, and phone numbers of available hospital. Counseling is provided by researcher or by a pediatric psychiatrist if needed.
This program could be adequately utilized for prevention of sexual abuse of children. It also will provide an intervention strategy for abused children. This educational program was distributed to all of the elementary school through the Ministry of Education and Human Resources Development.
Taehan Kanho Hakhoe chi 05/2003; 33(2):189-99.
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ABSTRACT: In cardiac myocytes, stimulation of alpha(1)-adrenoceptor (AR) leads to a hypertrophic phenotype. The G(h) protein (transglutaminase II, TGII) is tissue type transglutaminase and transmits the alpha(1B)-adrenoceptor signal with GTPase activity. Recently, it has been shown that the calreticulin (CRT) down-regulates both GTP binding and transglutaminase activities of TGII. To elucidate whether G(h) mediates norepinephrine-stimulated intracellular signal transductions leading to activation of extracellular signal-regulated kinases (ERKs) and neonatal rat cardiomyocyte hypertrophy, we examined the effects of G(h) on the activation of ERKs and inhibitory effects of CRT on alpha(1)-adrenoceptor/G(h) signaling. In neonatal rat cardiomyocytes, norepinephrine-induced ERKs activation was inhibited by an alpha(1)-adrenoceptor blocker (prazosin), but not by an beta-adrenoceptor blocker (propranolol). Overexpression of the G(h) protein stimulated norepinephrine-induced ERKs activation, which was inhibited by alpha-adrenoceptor blocker (prazosin). Co-overexpression of G(h) and CRT abolished norepinephrine-induced ERKs activation. Taken together, norepinephrine induces hypertrophy in neonatal rat cardiomyocytes through alpha(1)-AR stimulation and G(h) is partly involved in norepinephrine-induced MEK1,2/ERKs activation. Activation of G(h)-mediated MEK1,2/ERKs was completely inhibited by CRT.
The Journal of Steroid Biochemistry and Molecular Biology 02/2003; 84(1):101-7. · 3.05 Impact Factor
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ABSTRACT: Daily green tea drinking showed preventive effects on the progression of atherosclerosis. Although epigallocatechin-3-gallate [EGCG] has anti-proliferative effects on various cells, relatively little is known about the molecular mechanisms of the anti-proliferative effects of EGCG. To determine whether the transduction signals and protooncogene expression were affected by EGCG, this study investigated the molecular mechanism of the anti-proliferative effects in basic fibroblast growth factor (bFGF)-stimulated rat aortic smooth muscle cells (RAoSMCs). EGCG inhibited the proliferative response stimulated by 10% fetal bovine serum dose dependently in RAoSMCs (median inhibitory concentration [IC50]: 28.4 x 10(-6) M ). EGCG also inhibited the migration of bFGF-stimulated RAoSMCs in a dose-dependent manner, showing that 21.8 x 10(-6) M of EGCG significantly inhibited the migration by 75 +/- 5% in comparison with bFGF-stimulated migration. In RAoSMCs, EGCG dramatically inhibited Ras activation and c-jun N-terminal kinase (JNK) activity without affecting protein kinase C expression. Induction of c-jun mRNA stimulated by bFGF was significantly reduced dose dependently up to 87.3 x 10(-6) M of EGCG. These results indicate that the anti-proliferative effect of EGCG on RAoSMCs is partly Ras/JNK mediated, independent of protein kinase C, and is attributable to the downregulation of c-jun expression.
Journal of Cardiovascular Pharmacology 03/2002; 39(2):271-7. · 2.29 Impact Factor
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ABSTRACT: Proliferation and migration of vascular smooth muscle cells (VSMCs) are believed to contribute significantly to intimal thickening in atheroscleosis, restenosis, and venous bypass graft disease. Estrogen inhibits proliferation and migration of VSMCs. However, antiproliferative mechanisms of estrogen were not well elucidated yet. In this study, we investigated the antiproliferative effect of estrogen to determine whether the transduction signals and protooncogenes were affected in rat aortic smooth muscle cells (RASMCs). Estrogen inhibited the proliferative response stimulated by 5% fetal bovine serum (FBS) dose-dependently in RASMCs (IC50: 40 nM). In 0.5% serum-treated RASMCs, estrogen dramatically inhibited the activity of extracellular signal-regulated kinases (ERK) followed by inhibition of MEK1,2 activity in dose-dependent manner without affecting the other mitogen-activating protein kinases (MAPKs), c-jun N-terminal kinases (JNK) and p38. Induction of Elk-1 mRNA was significantly reduced dose-dependently up to 100 nM of estrogen. These results indicate that the antiproliferative effects of estrogen in RASMCs involved ERK inhibition followed by the inactivation of MEK1,2 and downregulation of Elk-1 expression.
The Journal of Steroid Biochemistry and Molecular Biology 02/2002; 80(1):85-90. · 3.05 Impact Factor
