Hwan Myung Lee

Hoseo University, Onyang, Chungcheongnam-do, South Korea

Are you Hwan Myung Lee?

Claim your profile

Publications (40)118.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Carvacrol (2-methyl-5-(1-methylethyl) phenol), a cyclic monoterpene, exerts protective activities in a variety of pathological states including tumor growth, inflammation, and oxidative stress. However, it is unknown whether carvacrol affects events in vascular cells during the development of atherosclerotic neointima. We investigated the effects of carvacrol on the migration and proliferation of rat aortic smooth muscle cells (RASMCs) and on vascular neointima formation. Carvacrol significantly inhibited platelet-derived growth factor (PDGF)-BB-stimulated RASMC migration and proliferation in a concentration-dependent manner. Cell viability was not affected by treatment with carvacrol. Carvacrol attenuated the expression of NADPH oxidase (NOX) 1 and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 in response to PDGF-BB. Moreover, carvacrol suppressed the PDGF-BB-stimulated generation of H2O2 and inhibited the activity of NOX in RASMCs. Treatment with carvacrol inhibited PDGF-BB-induced aortic sprout outgrowth, balloon injury-evoked vascular neointima formation, and expression of proliferating cell nuclear antigen in the neointima. These findings indicate that carvacrol inhibits migration and proliferation of RASMCs by suppressing the reactive oxygen species-mediated MAPK signaling pathway in these cells, thereby attenuating vascular neointimal formation. Carvacrol may be a promising agent for preventing vascular restenosis or atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 03/2015; 240(2):367-373. DOI:10.1016/j.atherosclerosis.2015.03.038 · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Azole antifungals such as ketoconazole are generally known to induce a variety of heart function side effects, e.g., long-QT syndrome and ventricular arrhythmias. However, a clear mechanism for the action of ketoconazole in heart cells has not been reported. In the present study, we assessed the correlation between ketoconazole-induced apoptosis and the alteration of genes in response to ketoconazole in rat cardiomyocytes. Cardiomyocyte viability was significantly inhibited by treatment with ketoconazole. Ketoconazole also stimulated H2O2 generation and TUNEL-positive apoptosis in a dose-dependent manner. DNA microarray technology revealed that 10,571 genes were differentially expressed by more than threefold in ketoconazole-exposed cardiomyocytes compared with untreated controls. Among these genes, parkin, which encodes a component of the multiprotein E3 ubiquitin ligase complex, was predominantly overexpressed among those classified as apoptosis- and reactive oxygen species (ROS)-related genes. The expression of parkin was also elevated in cardiomyocytes treated with exogenous H2O2. Moreover, cell viability and apoptosis in response to ketoconazole were inhibited in cardiomyocytes treated with ROS inhibitors and transfected with parkin siRNA. From the present findings, we concluded that ketoconazole may increase the expression of parkin via the ROS-mediated pathway, which consequently results in the apoptosis and decreased viability of cardiomyocytes.
    Archives of Toxicology 03/2015; DOI:10.1007/s00204-015-1502-0 · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The rupture of an atherosclerotic plaque is one of the main causes of coronary artery thrombotic occlusion, leading to myocardial infarction. However, the exact mechanism and causal risk factors for plaque rupture remain unclear. To identify a potential molecule that can influence atherosclerotic plaque rupture, we investigated protein expression in serum from patients with acute myocardial infarction (AMI) and stable angina (SA), using a proteomic analysis. The expressions of six proteins, including fibrinogen, fetuin-B, keratin 9, proapolipoprotein,and fibrinogen, were altered in serum from patients with AMI compared with SA. Of these, fetuin-B, proapolipoprtein,fibrinogen gamma-B chain precursors and fibrinogen expression were greater in serum from AMI than from SA patients. Increased fetuin-B expression in serum from AMI patients was also confirmed by Western blot analysis. Treatment with recombinant human fetuin-B increased the migration in monocytes and macrophages in a concentration-dependent manner. Fetuin-B also affected vascular plaque stabilize factors including the deposition of lipid and production of cytokines in macrophages, the activation of matrix metalloproteinase (MMP)-2 in monocytes, and the activations of apoptosis and MMP-2 in vascular smooth muscle cells. Moreover, in vivo administration of fetuin-B decreased the collagen accumulation and smooth muscle cell content and showed an increased number of macrophages in the vascular plaque. From these results, we suggest that fetuin-B may act as a modulator in the development of AMI. This study may provide a therapeutic advantage for patients at high risk of AMI.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: DJ-1 protein plays multifunctional roles including transcriptional regulation and scavenging oxidative stress; thus, it may be associated with the development of renal disorders. We investigated whether DJ-1 protein regulates the expression of (pro)renin receptor (PRR), a newly identified member of renin-angiotensin system. The levels of mRNA and protein were determined by real-time PCR and western blot, respectively. H2O2 production was tested by using fluorescence probe. Histone modification was determined by chromatin immunoprecipitation. The expression of PRR was significantly higher in the kidney from DJ-1 knockout mice (DJ-1(-/-)) compared with wild-type mice (DJ-1(+/+)). Histone deacetylase 1 recruitment at the PRR promoter was lower, and histone H3 acetylation and RNA polymerase II recruitment were higher in DJ-1(-/-) than in DJ-1(+/+). Knockdown or inhibition of histone deacetylase 1 restored PRR expression in mesangial cells from DJ-1(+/+). H2O2 production was greater in DJ-1(-/-) cells compared with DJ-1(+/+) cells. These changes in PRR expression and epigenetic modification in DJ-1(-/-) cells were induced by H2O2 treatment and reversed completely by addition of an antioxidant reagent. Prorenin-stimulated ERK1/2 phosphorylation was greater in DJ-1(-/-) than in DJ-1(+/+) cells and this was inhibited by a PRR-inhibitory peptide, and by AT1 and AT2 receptor inhibitors. The expression of renal fibrotic genes was higher in DJ-1(-/-) than in DJ-1(+/+) cells and decreased in PRR-knockdown DJ-1(-/-) cells. We conclude that DJ-1 protein regulates the expression of renal PRR through H2O2-mediated epigenetic modification. We suggest that renal DJ-1 protein may be an important molecule in the acceleration of renal pathogenesis through PRR regulation. Copyright © 2013. Published by Elsevier B.V.
    Biochimica et Biophysica Acta (BBA) - General Subjects 11/2014; 1850(2):426-434. DOI:10.1016/j.bbagen.2014.11.017 · 3.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Artemisia montana Pampan (Compositae) (AMP) contains various compounds, including phenolic acids, alkaloids, and essential oil. It has been widely used in oriental medicine due to a variety of biological effects. However, the biological activity of the essential oil from AMP (AMPEO) on skin has not been investigated. In the present study, AMPEO was evaluated for its composition and its effect on cellular events (migration and proliferation) related to skin regeneration using normal human keratinocytes (HaCats). AMPEO, which was extracted by steam distillation, contained 42 components. AMPEO increased proliferation in HaCats in a dose-dependent manner (EC 50, 8.5 ng/mL) and did not affect migration. AMPEO also enhanced the phosphorylation of Akt and ERK 1/2 and induced the synthesis of type IV collagen, but not type I collagen in HaCats. In addition, AMPEO promoted wound closure in the dorsal side skin of rat tail. These results demonstrated that AMPEO extracted by steam distillation induced proliferation and synthesis of type IV collagen in human skin keratinocytes, and may thereby exert positive effects on skin regeneration and wound healing in human skin.
    Natural product communications 11/2014; 9(11):1619-22. · 0.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Context: Chrysanthemum boreale Makino (Compositae) (CBM) is a traditional medicine that has been used for the prevention or treatment of various disorders; it has various properties including antioxidation, anti-inflammation, and antitumor. Objective: The present study was designed to explore the in vitro effect of CBM flower floral water (CBMFF) on atherosclerosis-related responses in rat aortic smooth muscle cells (RASMCs). Materials and methods: CBMFF was extracted from CBM flower by steam distillation and analyzed using gas chromatography–mass spectrometry. The anti-atherosclerosis activity of CBMFF was tested by estimating platelet-derived growth factor (PDGF)-BB (10 ng/mL)-induced proliferation and migration levels and intracellular kinase pathways in RASMCs at CBMFF concentrations of 0.01–100 μM and analyzing ex vivo aortic ring assay. Results: Gas chromatography–mass spectrometry showed that the CBMFF contained a total of seven components. The CBMFF inhibits PDGF-BB-stimulated RASMC migration and proliferation (IC50: 0.010 μg/mL). Treatment of RASMCs with PDGF-BB induced PDGFR-β phosphorylation and increased the phosphorylations of MAPK p38 and ERK1/2. CBMFF addition prevented PDGF-BB-induced phosphorylation of these kinases (IC50: 008 and 0.018 μg/mL, for p38 MAPK and ERK1/2, respectively), as well as PDGFR-β (IC50: 0.046 μg/mL). Treatment with inhibitors of PDGFR, P38 MAPK, and ERK1/2 decreased PDGF-BB-increased migration and proliferation in RASMCs. Moreover, the CBMFF suppressed PDGF-BB-increased sprout outgrowth of aortic rings (IC50: 0.047 μg/mL). Discussion and conclusion: These results demonstrate that CBMFF may inhibit PDGF-BB-induced vascular migration and proliferation, most likely through inhibition of the PDGFR-β-mediated MAPK pathway; therefore, the CBMFF may be promising candidate for the development of herbal remedies for vascular disorders.
    Pharmaceutical Biology 10/2014; DOI:10.3109/13880209.2014.941882 · 1.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the effect of essential oil from the flower of Chrysanthemum boreale Makino (CBMEO) on growth of human keratinocytes (HaCaTs) and explored a possible mechanism for this response. CBMEO was extracted using the steam distillation method. CBMEO contained a total of 33 compounds. CBMEO stimulated HaCaT proliferation (EC50, 0.028 μg/mL) and also induced phosphorylation of Akt and ERK1/2 in HaCaTs (EC50, 0.007 and 0.005 μg/mL, for phosphorylated Akt and ERK1/2, respectively). Moreover, CBMEO promoted wound closure in the dorsal side skin of rat tail. This study demonstrated that CBMEO can stimulate growth of human skin keratinocytes, probably through the Akt and ERK1/2 pathways. Therefore, CBMEO may be helpful in skin regeneration and wound healing in human skin, and may also be a possible cosmetic material for skin beauty.
    Natural Product Research 08/2014; 29(6):1-3. DOI:10.1080/14786419.2014.952231 · 1.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: DJ-1/park7, a multifunctional protein, may play essential roles in the vascular system. However, the function of DJ-1/park7 in vascular contractility has remained unclear. The present study was designed to investigate whether the DJ-1/park7 is involved in the regulation of vascular contractility and systolic blood pressure (SBP). Norepinephrine (NE) elevated contraction in endothelium-intact vessels in a dose-dependent manner, to a greater extent in DJ-1/park7 knockout (DJ-1/park7(-/-)) mice than in wild-type (DJ-1/park7(+/+)) mice. Acetylcholine inhibited NE-evoked contraction in endothelium-intact vessels, and this was markedly impaired in DJ-1/park7(-/-) mice compared with DJ-1/park7(+/+) mice. Nitric oxide (NO) production (82.1±2.8% of control) and endothelial NO synthase (eNOS) expression (61.7±8.9%) were lower, but H2O2 production (126.4±8.6%) was higher, in endothelial cells from DJ-1/park7(-/-) mice than in those from DJ-1/park7(+/+) controls; these effects were reversed by DJ-1/park7-overexpressing endothelial cells from DJ-1/park7(-/-) mice. Histone deacetylase (HDAC)-1 recruitment and H3 histone acetylation at the eNOS promoter were elevated and diminished, respectively, in DJ-1/park7(-/-) mice compared with DJ-1/park7(+/+) controls. Moreover, SBP was significantly elevated in DJ-1/park7(-/-) mice compared with DJ-1/park7(+/+) controls, but this elevation was inhibited in mice treated with valproic acid, an inhibitor of class I HDACs including HDAC-1. These results demonstrate that DJ-1/park7 protein may be implicated in the regulation of vascular contractility and blood pressure, probably by the impairment of NO production through H2O2-mediated epigenetic inhibition of eNOS expression.
    Cardiovascular Research 12/2013; DOI:10.1093/cvr/cvt274 · 5.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite the altered expression of Tie receptors and angiopoietin ligands during hypoxic conditions, the effect of hypoxia on Tie-mediated endothelial responses has not been elucidated. In this study, we found that hypoxia increased Tie receptor expression but attenuated angiopoietin-1(Ang1)-induced Tie2 activity, including Tie2 phosphorylation, Tie2 downstream signaling activation, and endothelial cell tube formation. However, Ang1 binding to endothelial cells was increased during hypoxic conditions. We demonstrated that Tie1 suppression restored the Tie2 activity and that Tie1-mediated Tie2 suppression was independent of tyrosine phosphatase activity. These results suggest that under hypoxic conditions, Tie1 is critical for reducing Ang1-induced Tie2 activity and angiogenesis.
    Biochemical and Biophysical Research Communications 06/2013; 436(4). DOI:10.1016/j.bbrc.2013.06.018 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: This study was attempted to identify new molecules expressed on the plasma membrane of human umbilical vein endothelial cells (HUVECs) using monoclonal antibody-based proteomics technology and to determine the effect of the identified antibody on vascular reactivity. Methods: Twenty-two antibodies were developed from rats inoculated with HUVECs, and their effects were determined by observing vascular reactivity. Results: Among the 22 antibodies, the C-7 antibody significantly inhibited endothelium-dependent vasorelaxation in response to acetylcholine (ACh) but not to histamine. Moreover, the C-7 antibody did not affect norepinephrine-induced contraction in either the endothelium-intact or -denuded aorta. A proteomics study involving immunoprecipitation of the C-7 antibody with biotinylated HUVECs showed that this antibody binds to plasma membrane proteins corresponding to immunoglobulin heavy chain (VHDJ region), chaperonin-containing T-complex polypeptide 1 and α-actinin 4. The muscarinic M3 ACh receptor and α-actinin 4 were colocalized on the plasma membrane of HUVECs, and the colocalization was found to increase in response to ACh and was inhibited by pretreatment with the C-7 antibody. Conclusions: These results demonstrate that monoclonal C-7 antibody exerts an inhibitory effect on endothelium-dependent vasorelaxation induced by ACh and that this response may at least partially result from the inhibition of α-actinin 4.
    Journal of Vascular Research 05/2013; 50(3):210-220. DOI:10.1159/000350588 · 2.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress, has been recently rediscovered to inhibit Rac1 in neutrophils and macrophages, thereby inhibiting Rac1-linked functions of these cells, including reactive oxygen species production through NADPH oxidase activation, phagocytosis, chemotaxis, and cytokine release. In vascular smooth muscle cells (VSMCs), reactive oxygen species also induce abnormal proliferation and migration leading to progression of atherosclerosis. Based upon the involvement of reactive oxygen species in phagocytic cells and VSMCs during the atherosclerotic process, we hypothesized that 8-OHdG could have antiatherosclerotic action and tested this hypothesis in an experimentally induced atherosclerosis in mice. Partially ligated ApoE knockout mice, a more physiologically relevant model of low and oscillatory flow, developed an advanced lesion in 2 weeks, and orally administered 8-OHdG significantly reduced plaque formation along with reduced superoxide formation, monocyte/macrophage infiltration, and extracellular matrix (ECM) accumulation. The effects of 8-OHdG observed in primary VSMCs were consistent with the in vivo effects of 8-OHdG and were inhibitory to angiotensin II or platelet-derived growth factor-induced production of reactive oxygen species, proliferation, migration, and ECM production. Also, angiotensin II-induced Rac1 activity in VSMCs was significantly inhibited by 8-OHdG, and transfection of constitutively active Rac1 reversed the inhibitory effect of 8-OHdG on VSMC activation. Molecular docking study showed that 8-OHdG stabilizes Rac1-GEF complex, indicating the physical contact of 8-OHdG with Rac1. These findings highly suggest that the antiatherosclerotic effect of 8-OHdG is mediated by inhibition of Rac1 activity. In conclusion, our results show a novel action of orally active 8-OHdG in suppressing atherosclerotic plaque formation in vivo and VSMC activation in vitro through inhibition of Rac1, which emphasizes a new therapeutic avenue to benefit atherosclerosis.
    Free Radical Biology and Medicine 04/2012; 53(1):109-21. DOI:10.1016/j.freeradbiomed.2012.03.023 · 5.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 8-Hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative stress, has been recently rediscovered to inhibit Rac1 in neutrophils and macrophages, thereby inhibiting Rac1-linked functions of these cells including reactive oxygen species production through NADPH oxidase activation, phagocytosis, chemotaxis, and cytokine release. In vascular smooth muscle cells (VSMCs), reactive oxygen species also induce abnormal proliferation and migration leading to progression of atherosclerosis. Based upon the involvement of reactive oxygen species in phagocytic cells and VSMCs during atherosclerotic process, we hypothesized that 8-OHdG could have anti-atherosclerotic action and tested this hypothesis in an experimentally induced atherosclerosis in mice. Partially ligated ApoE knockout (KO) mice, a more physiologically relevant model of low and oscillatory flow, developed an advanced lesion in 2 weeks and orally administered 8-OHdG significantly reduced plaque formation along with reduced superoxide formation, monocyte/macrophage infiltration, and extracellular matrix (ECM) accumulation. The effects of 8-OHdG observed in primary VSMCs were consistent with the in vivo effect of 8-OHdG which were inhibitory to angiotensin II or platelet-derived growth factor-induced production of reactive oxygen species, proliferation, migration, and ECM production. Also, angiotensin II-induced Rac1 activity in VSMCs were significantly inhibited by 8-OHdG and transfection of constitutively active Rac1 reversed the inhibitory effect of 8-OHdG on VSMC activation. Molecular docking study showed that 8-OHdG stabilizes Rac1-GEF complex indicating the physical contact of 8-OHdG with Rac1. These findings highly suggest that the anti-atherosclerotic effect of 8-OHdG is mediated by inhibition of Rac1 activity. In conclusion, our results showed a novel action of orally active 8-OHdG in suppressing atherosclerotic plaque formation in vivo and VSMC activation in vitro through inhibition of Rac1, which emphasizes a new therapeutic avenue to benefit atherosclerosis.
    Free Radical Biology and Medicine 04/2012; · 5.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Liquid crystalline behavior of dimesogenic compounds opens a new area of research in liquid crystals science. The term ‘dimesogenic compounds’ describes thermotropic compounds consisting of two mesogenic units linked through a central spacer such as polymethylene and oligosiloxyl groups. The two mesogenic units may or may not be identical. When they are identical, they are occasionally called twin or siamese compounds.
    Journal of Industrial and Engineering Chemistry 01/2012; 18(1). DOI:10.1016/j.jiec.2011.11.037 · 2.06 Impact Factor
  • 01/2011; 15(1):J6-J6. DOI:10.1540/heikatsukinzashi.15.J6
  • [Show abstract] [Hide abstract]
    ABSTRACT: The roles of Src homology domain 2-containing protein tyrosine phosphatase 2 (SHP-2) and its signaling in atherosclerosis have not been explored. Therefore, we investigated the roles of SHP-2 in the movement of rat aortic smooth muscle cells (RASMCs) and in the neointima formation of the carotid artery. Platelet-derived growth factor (PDGF)-BB (1 - 20 ng/ml) increased the activity and phosphorylation of SHP-2 and migration in RASMCs and these were suppressed by SHP-2 inhibitor NSC-87877 (30 µM) and small interfering RNA of SHP-2. PDGF-BB increased the phosphorylations of spleen tyrosine kinase (Syk) and p38 mitogen-activated protein kinase (MAPK), which were recovered by inhibition of SHP-2. Moreover, PDGF-BB increased the levels of reactive oxygen species (ROS) and ROS inhibitors decreased PDGF-BB-increased migration. Treatment of RASMCs with H(2)O(2) (100 µM) increased cell migration and SHP-2 phosphorylation and also enhanced the phosphorylation levels of Syk and p38 MAPK. Oral administration of NSC-87877 (10 mg/kg) significantly suppressed neointima formation in a rat model of carotid artery injury. These results suggest that the activity of SHP-2 is controlled by ROS and is positively involved in the regulation of PDGF-BB-induced RASMC migration and neointima formation.
    Journal of Pharmacological Sciences 01/2011; 115(2):164-75. DOI:10.1254/jphs.10250FP · 2.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The mechanism including changes of proteome within cavernosal tissue after cavernous nerve injury were not evaluated. We performed proteomics and functional analysis to identify proteins of penile corpus cavernosum whose expression was or was not altered by cavernous nerve resection (CNR).
    01/2011; 29(2):111. DOI:10.5534/kja.2011.29.2.111
  • [Show abstract] [Hide abstract]
    ABSTRACT: 3-Morpholinosydnonimine (SIN-1) affects vascular smooth muscle cell migration and proliferation, processes essential for atherosclerosis. However, the mechanism by which SIN-1 exerts these effects has not been elucidated. We used 2-DE followed by MALDI-TOF/TOF MS to identify responses in protein expression to SIN-1 in rat aortic smooth muscle. Platelet-derived growth factor-BB increased cell migration and proliferation in rat aortic smooth muscle cells, and subsequent SIN-1 treatment inhibited it. Administration of SIN-1 in vivo attenuated neointima formation in balloon-injured rat carotid arteries. Proteomic analysis showed that glutathione peroxidase and 40S ribosomal protein S12 were differentially expressed in aortic strips exposed to SIN-1. Expression of annexin A2 was decreased by SIN-1. Platelet-derived growth factor-BB-induced cell migration was increased and inhibited in rat aortic smooth muscle cells with overexpression and knockdown of annexin A2 gene, respectively. The expression of annexin A2 was increased in vascular neointima compared with the intact control, which was inhibited by SIN-1 treatment. These results demonstrate that SIN-1 may attenuate vascular neointima formation by inhibiting annexin A2-mediated migration. Therefore, annexin A2 may be a potential target for therapeutic strategies for atherosclerosis.
    Proteomics 01/2011; 11(2):193-201. DOI:10.1002/pmic.200900834 · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We characterized a Kunitz-type protease inhibitor (Gm KTPI) obtained from the hemolymph of Galleria mellonella larvae immunized with Escherichia coli. The structural analysis of the cloned cDNA showed that it consists of 56 residues derived from the precursor of 75 amino acids. The peptide was constitutively produced in the fat bodies, but not in the midgut nor the integument of larvae. In our analysis of stage-dependent expression, its transcript was detected within the midgut, the fat bodies and the integument of the prepupae, which undergo tissue remodeling. The inhibition assays showed that Gm KTPI was capable of inhibiting only the trypsin-like activity of the larval midgut extracts. Furthermore, it was determined that Gm KTPI induced the activation of extracellular signal-regulated kinase (ERK) in the fat bodies and integument cells, and this kinase is known to perform a central role in cell proliferation signaling. Its effect on ERK activation was also verified in a control experiment using a human endothelial cell culture. Collectively, it was suggested that Gm KTPI might be responsible for the protection of other tissues against proteolytic attack by trypsin-like protease(s) from larval midgut during metamorphosis, and might play a role in the proliferation of cells in the fat body and integument.
    Insect biochemistry and molecular biology 12/2010; 40(12):873-82. DOI:10.1016/j.ibmb.2010.08.007 · 3.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: While intercellular adhesion molecule-1 (ICAM-1) is a transmembrane protein, two types of extracellular ICAM-1 have been detected in cell culture supernatants as well as in the serum: a soluble form of ICAM-1 (sICAM-1) and a membranous form of ICAM-1 (mICAM-1) associated with exosomes. Previous observations have demonstrated that sICAM-1 cannot exert potent immune modulatory activity due to its low affinity for leukocyte function-associated antigen-1 (LFA-1) or membrane attack complex-1. In this report, we initially observed that human cancer cells shed mICAM-1(+)-exosomes but were devoid of vascular cell adhesion molecule-1 and E-selectin. We demonstrate that mICAM-1 on exosomes retained its topology similar to that of cell surface ICAM-1, and could bind to leukocytes. In addition, we show that exosomal mICAM-1 exhibits potent anti-leukocyte adhesion activity to tumor necrosis factor-alpha-activated endothelial cells compared to that of sICAM-1. Taken together with previous findings, our results indicate that mICAM-1 on exosomes exhibits potent immune modulatory activity.
    Biochemical and Biophysical Research Communications 06/2010; 397(2):251-6. DOI:10.1016/j.bbrc.2010.05.094 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS) activity, is known to play important roles in modulating both NO and superoxide production during vascular diseases such as atherosclerosis. However, the role of BH4 in functions of vascular smooth muscle cells is not fully known. In this study, we tested the effects of BH4 and dihydrobiopterin (BH2), a BH4 precursor, on migration and proliferation in response to platelet-derived growth factor-BB (PDGF-BB) in rat aortic smooth muscle cells (RASMCs). Cell migration and proliferation were measured using a Boyden chamber and a 5-bromo-2'-deoxyuridine incorporation assay, respectively, and these results were confirmed with an ex vivo aortic sprout assay. Cell viability was examined by 2,3-bis [2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide assays. BH4 and BH2 decreased PDGF-BB-induced cell migration and proliferation in a dose-dependent manner. The inhibition of cell migration and proliferation by BH4 and BH2 was not affected by pretreatment with N(G)-nitro-L-arginine methyl ester, a NOS inhibitor. Moreover, the sprout outgrowth formation of aortic rings induced by PDGF-BB was inhibited by BH4 and BH2. Cell viability was not inhibited by BH4 and BH2 treatment. The present results suggest that BH4 and BH2 may inhibit PDGF-stimulated RASMC migration and proliferation via the NOS-independent pathway. Therefore, BH4 and its derivative could be useful for the development of a candidate molecule with an NO-independent anti-atherosclerotic function.
    Korean Journal of Physiology and Pharmacology 06/2010; 14(3):177-83. DOI:10.4196/kjpp.2010.14.3.177 · 1.26 Impact Factor

Publication Stats

500 Citations
118.96 Total Impact Points

Institutions

  • 2009–2014
    • Hoseo University
      • College of Natural Sciences
      Onyang, Chungcheongnam-do, South Korea
  • 2006–2013
    • Konkuk University
      • School of Medicine
      Sŏul, Seoul, South Korea
  • 2010
    • Pohang University of Science and Technology
      • Division of Molecular and Life Sciences
      Antō, North Gyeongsang, South Korea
  • 2007
    • Chungnam National University
      Daiden, Daejeon, South Korea
  • 2002–2004
    • Kyung Hee University
      • Graduate School of East-West Medical Science
      Sŏul, Seoul, South Korea