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Jun-Seop Park,
Tae-Sang Jung,
Yang-Ho Noh,
Woo-Sung Kim,
Won-Ick Park,
Young-Soo Kim,
In-Kyo Chung,
Uy Dong Sohn,
Soo-Kyung Bae, Moon-Kyoung Bae,
Hye-Ock Jang,
Il Yun
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ABSTRACT: The purpose of this study is to investigated the mechanism of pharmacological action of local anesthetic and provide the basic information about the development of new effective local anesthetics. Fluorescent probe techniques were used to evaluate the effect of lidocaine·HCl on the physical properties (transbilayer asymmetric lateral and rotational mobility, annular lipid fluidity and protein distribution) of synaptosomal plasma membrane vesicles (SPMV) isolated from bovine cerebral cortex, and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from the SPMV. An experimental procedure was used based on selective quenching of 1,3-di(1-pyrenyl)propane (Py-3-Py) and 1,6-diphenyl-1,3,5-hexatriene (DPH) by trinitrophenyl groups, and radiationless energy transfer from the tryptophans of membrane proteins to Py-3-Py. Lidocaine·HCl increased the bulk lateral and rotational mobility of neuronal and model membrane lipid bilayes, and had a greater fluidizing effect on the inner monolayer than the outer monolayer. Lidocaine·HCl increased annular lipid fluidity in SPMV lipid bilayers. It also caused membrane proteins to cluster. The most important finding of this study is that there is far greater increase in annular lipid fluidity than that in lateral and rotational mobilities by lidocaine·HCl. Lidocaine·HCl alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that lidocaine, in addition to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membrane lipid.
Korean Journal of Physiology and Pharmacology 12/2012; 16(6):413-22. · 0.96 Impact Factor
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ABSTRACT: OBJECTIVE: Porphyromonas gingivalis is a major periodontopathogen that plays a role in the pathogenesis of periodontal disease. In this study, we investigated the effect of 18alpha-glycyrrhetinic acid (18α-GA), a natural triterpenoid compound derived from licorice root extract, on P. gingivalis lipopolysaccharide (LPS)-induced vascular permeability, which is a hallmark of inflammatory diseases such as periodontitis. METHODS: The inhibitory effects of 18α-GA on endothelial permeability were determined by measuring in vivo and in vitro endothelial permeability. Endothelial cells were pretreated with 18α-GA before exposure to P. gingivalis LPS, and total RNA or proteins were extracted and analyzed by reverse transcription polymerase chain reaction or western blotting. RESULTS: Porphyromonas gingivalis LPS-induced endothelial permeability was significantly inhibited by 18α-GA both in vivo and in vitro. 18α-GA reduces P. gingivalis LPS-induced gap formation of endothelial cells. Importantly, 18α-GA modulated the expression and secretion of interleukin-8 (IL-8), a key inducer of vascular permeability, by downregulating nuclear factor-κB (NF-κB). 18α-GA suppressed P. gingivalis LPS-stimulated inhibitor of kappa B (IκB) kinase activation, IκBα phosphorylation, and nuclear translocation of NF-κB. CONCLUSIONS: Overall, these findings suggest that 18α-GA significantly reduces P. gingivalis LPS-induced vascular permeability by repressing NF-κB-dependent endothelial IL-8 production, suggesting its therapeutic potential in P. gingivalis-related vascular diseases.
Agents and Actions 10/2012; · 1.59 Impact Factor
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Hyung-Jin Joo,
Shin-Ho Ahn,
Hang-Rae Lee,
Sung-Woo Jung,
Chang-Won Choi,
Min-Seok Kim, Moon-Kyoung Bae,
In-Kyo Chung,
Soo-Kyoung Bae,
Hye-Ock Jang,
Il Yun
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ABSTRACT: The structures of the intact synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortexs, and the outer and the inner monolayer separately, were evaluated with 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) as fluorescent reporters and trinitrophenyl groups as quenching agents. The methanol increased bulk rotational and lateral mobilities of SPMVs lipid bilayers. The methanol increased the rotational and lateral mobilities of the outer monolayers more than of the inner monolayers. n-(9-Anthroyloxy)stearic acid (n-AS) were used to evaluate the effect of the methanol on the rotational mobility at the 16, 12, 9, 6, and 2 position of aliphatic chains present in phospholipids of the SPMVs outer monolayers. The methanol decreased the anisotropy of the 16-(9-anthroyloxy)palmitic acid (16-AP), 12-(9-anthroyloxy)stearic acid (12-AS), 9-(9-anthroyloxy)stearic acid (9-AS), and 6-(9-anthroyloxy)stearic acid (6-AS) in the SPMVs outer monolayer but it increased the anisotropy of 2-(9-anthroyloxy)stearic acid (2-AS) in the monolayers. The magnitude of the increased rotational mobility by the methanol was in the order at the position of 16, 12, 9, and 6 of aliphatic chains in phospholipids of the outer monolayers. Furthermore, the methanol increased annular lipid fluidity and also caused membrane proteins to cluster. The important finding is that was far greater increase by methanol in annular lipid fluidity than increase in lateral and rotational mobilities by the methanol. Methanol alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that methanol, in additions to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membranes lipids.
Korean Journal of Physiology and Pharmacology 08/2012; 16(4):255-64. · 0.96 Impact Factor
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Tae-Sang Jung,
Jeong-Kuk Kim,
Ki Yong Nam,
Kyung-Zoo Lee,
Sung-Key Lee,
Wang Bong Park,
Myung-Suk Ko,
Won-Il Kim,
Byung-Kug Kim,
Byung Soo Kim,
Young Chan Jeon,
In Kyo Chung, Moon Kyoung Bae,
Hye-Ock Jang,
Il Yun
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ABSTRACT: The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of dopamine·HCl
(DA) and chlorpromazin·HCl (CPZ). Radiationless energy transfer from the surface fluorescent probe, 1-anilinonaphthalene-8-sulfonic
acid, to the hydrophobic fluorescent probe, bispyrenylpropane (Py-Py), was used to examine the effects of DA and CPZ on the
thickness (D) of the liposomal lipid bilayers prepared with total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from
neuronal membranes. The thickness (D) of intact SPMVTL and SPMVPL (37°C, pH 7.4) were 0.914 ± 0.010 and 0.886 ± 0.009 (arbitrary
units, n = 5), respectively. DA decreased the thickness of both SPMVTL and SPMVPL in a dose-dependent manner with a significant
decrease in thickness observed even at 40 × 10−9 M and 40 × 10−9 M, respectively. On the other hand, CPZ increased the thickness of both SPMVTL and SPMVPL in a dose-dependent manner with
a significant increase in thickness observed even at 35 × 10−5 M and 35 × 10−5 M, respectively. The sensitivities to the decreasing and increasing effect of the membrane lipid bilayers thickness by DA
and CPZ, respectively, differed according to the liposomes in descending order of SPMVPL and SPMVTL. The decreasing and increasing
action of DA and CPZ, respectively, on the membrane thickness had many effects that may be responsible for the dopaminergic
receptor-DA and -CPZ interaction as well as the protein-lipid interaction.
Key wordsDopamine·HCl-Chlorpromazine·HCl-Membrane thickness-Fluorescence quenching technique-Liposomes
Archives of Pharmacal Research 04/2012; 33(5):737-744. · 1.59 Impact Factor
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ABSTRACT: Thromboxane synthase (TXAS) is an enzyme that catalyzes the synthesis of thromboxane A(2) (TXA(2)). Overexpression of TXAS is associated with a variety of vascular diseases. Recently, we reported that visfatin, a novel adipokine, exhibits angiogenic actions. In this study, we showed that visfatin increased mRNA and protein levels of TXAS and stimulated TXA(2) biosynthesis in vascular endothelial cells. In addition, visfatin induced the expression and secretion of interleukin-8 (IL-8), which is blocked by a TXAS inhibitor and by the transfection of siRNA specific for TXAS. Furthermore, the inhibition of TXAS activity and blockade of the IL-8 receptor attenuated visfatin-induced endothelial angiogenesis. Together, these results showed that visfatin promoted IL-8 production by upregulation of TXAS, leading to angiogenic activation in endothelial cells.
Biochemical and Biophysical Research Communications 02/2012; 418(4):662-8. · 2.48 Impact Factor
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ABSTRACT: Obesity is frequently associated with breast cancer. Such associations are possibly mediated by adipokines. Visfatin, an adipokine, has recently been shown to be related to the development and progression of breast cancer. Therefore, the down-regulation of visfatin may be a novel strategy for breast cancer therapy. Curcumin has anticancer activities by modulating multiple signaling pathways and genes. The purpose of this study was to investigate whether visfatin gene expression is affected by curcumin in human breast cancer cells and to characterize the functional role of visfatin in breast cancer. We found that the mRNA and protein levels of visfatin were down-regulated by curcumin in MDA-MB-231, MDA-MB-468, and MCF-7 breast cancer cells, along with decreased activity of constitutive nuclear factor (NF)-κB. We confirmed the repressive effect of curcumin on visfatin transcription by performing a visfatin promoter-driven reporter assay and identified two putative NF-κB-binding sites on visfatin promoter that are important for this effect. EMSA and chromatin immunoprecipitation analysis indicated the binding of p65 to the visfatin promoter, which was effectively blocked by curcumin. Enforced expression of p65 protein increased visfatin promoter activity, whereas blocking NF-κB signaling suppressed visfatin gene expression. Visfatin could enhance the invasion of MDA-MB-231 cells and also attenuate curcumin-induced inhibition of cell invasion; on the other hand, visfatin knockdown by small interfering RNA led to the reduction of cell invasion. Our data demonstrate, for the first time, that curcumin down-regulates visfatin gene expression in human breast cancer cells by a mechanism that is, at least in part, NF-κB dependent and suggest that visfatin may contribute to breast cancer cell invasion and link obesity to breast cancer development and progression.
Endocrinology 12/2011; 153(2):554-63. · 4.46 Impact Factor
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ABSTRACT: The angiogenic and inflammatory functions of visfatin and its effect on vascular cells, are fairly well known. However, its role within the nervous system remains largely unclear. To gain insight into this area, we studied the neuritogenic effect of visfatin on PC12 rat pheochromocytoma cells. We investigated whether visfatin gene expression, which is upregulated by hypoxia in cancer cells, is associated with neuritogenesis in PC12 cells. Using RT-PCR, Western blot analysis, ELISA, morphological observations, and immunostaining, we initially showed that CoCl(2), a hypoxic mimetic agent, upregulated visfatin gene expression along with neurite outgrowth in PC12 cells. We also showed that visfatin stimulated neurite outgrowth in PC12 cells. Moreover, in PC12 cells, visfatin evoked the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), which is closely linked to neuritogenesis. Visfatin-induced outgrowth of neurites was prevented by inhibition of the ERK1/2 pathway. Taken together, our results demonstrate for the first time that visfatin induces neurite outgrowth in PC12 cells via the activation of an ERK-dependent pathway, and suggest that visfatin may exert various biological, physiological, and pathological functions in not only the vascular system but also the nervous system.
Neuroscience Letters 09/2011; 504(2):121-6. · 2.11 Impact Factor
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ABSTRACT: Neuromedin B (NMB), a member of the mammalian bombesin-like peptide family, and its receptor were aberrantly expressed in vascularized solid tumors. Here, the NMB receptor (NMB-R) antagonist PD168368 specifically inhibited both NMB-induced in vivo and in vitro angiogenesis. In addition, PD168368 showed growth inhibitory effects on MDA-MB-231 breast cancer cells by inducing cell cycle arrest and apoptosis. Furthermore, PD168368 effectively suppressed tumor growth in a xenograft model of breast tumor in vivo. Overall, NMB-R antagonist exhibited a significant antitumor activity by simultaneously inhibiting neovascularization and cancer cell growth, thereby suggesting that NMB-R could be a potential therapeutic target for cancer treatment.
Cancer letters 08/2011; 312(1):117-27. · 4.86 Impact Factor
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Yun-Hee Bae,
Hyun-Joo Park,
Su-Ryun Kim,
Jee-Young Kim,
Youra Kang,
Jung-Ae Kim,
Hee-Jun Wee,
Ryoichiro Kageyama,
Jin Sup Jung, Moon-Kyoung Bae,
Soo-Kyung Bae
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ABSTRACT: Our aims were to determine the role of Notch1 in mediating visfatin-induced angiogenesis and to explore potential target genes involved.
Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro, ex vivo, and in vivo. Visfatin increased γ-secretase activity, Notch1 cleavage and activation, and Hes1 gene induction. Visfatin also stimulated fibroblast growth factor-2 (FGF-2) gene expression in a Notch1-dependent manner. Enforced expression of active Notch1 intracellular domain increased FGF-2 protein levels and stimulated endothelial tube formation, whereas blocking Notch1 signalling or knockdown of Notch1 by small interfering RNA suppressed visfatin-induced FGF-2 up-regulation and angiogenesis. Reporter analysis of FGF-2 promoter revealed the presence of CSL (CBF-1, suppressor of hairless, LAG-1)-binding site, and chromatin immunoprecipitation analysis demonstrated the binding of Notch1-CSL complex to this site in response to visfatin.
Our data provide the first example of Notch1-dependent endothelial FGF-2 induction by visfatin and of Notch1 activation in visfatin-stimulated endothelial angiogenesis, suggesting that the signalling axis of visfatin/Notch1/angiogenic factors like FGF-2 might be a valuable target for pathological angiogenesis.
Cardiovascular research 02/2011; 89(2):436-45. · 5.80 Impact Factor
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ABSTRACT: Orexin-A, a neuropeptide originally discovered in the hypothalamus, is found in peripheral organs, as well as in the central nervous system, and is involved in the regulation of food intake, energy homeostasis, and cardiovascular functions. In this study, we report that orexin-A induces invivo neovascularization in a mouse Matrigel plug and ex vivo sprouting of endothelial cells in rat aortic rings. We also show that orexin-A increases migration and tube formation in human umbilical vein endothelial cells (HUVECs), and this effect is mediated by orexin receptors on endothelial cells. Moreover, orexin-A activates the extracellular signal-regulated kinase 1/2 (ERK1/2) in HUVECs, which is closely linked to angiogenic responses. The inhibition of ERK activation significantly suppresses orexin-A-stimulated endothelial angiogenesis. Taken together, our results indicate that orexin-A functions as a new proangiogenic peptide and requires MEK/ERK-dependent pathway for its angiogenic actions. These results suggest orexin-A and its receptor may act as important modulators of angiogenesis under pathophysiological conditions.
Biochemical and Biophysical Research Communications 10/2010; 403(1):59-65. · 2.48 Impact Factor
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Su-Ryun Kim,
Soo-Kyung Bae,
Hyun-Joo Park,
Mi-Kyoung Kim,
Koanhoi Kim,
Shi-Young Park,
Hye-Ock Jang,
Il Yun,
Yung-Jin Kim,
Mi-Ae Yoo, Moon-Kyoung Bae
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ABSTRACT: Thromboxane A(2) (TXA(2)), a major prostanoid formed from prostaglandin H(2) by thromboxane synthase, is involved in the pathogenesis of a variety of vascular diseases. In this study, we report that TXA(2) mimetic U46619 significantly increases the endothelial permeability both in vitro and in vivo. U46619 enhanced the expression and secretion of interleukin-8 (IL-8), a major inducer of vascular permeability, in endothelial cells. Promoter analysis showed that the U46619-induced expression of IL-8 was mainly regulated by nuclear factor-kappaB (NF-kappaB). U46619 induced the activation of NF-kappaB through IkappaB kinase (IKK) activation, IkappaB phosphorylation and NF-kappaB nuclear translocation. Furthermore, the inhibition of IL-8 or blockade of the IL-8 receptor attenuated the U46619-induced endothelial cell permeability by modulating the cell-cell junctions. Overall, these results suggest that U46619 promotes vascular permeability through the production of IL-8 via NF-kappaB activation in endothelial cells.
Biochemical and Biophysical Research Communications 07/2010; 397(3):413-9. · 2.48 Impact Factor
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Tae-Sang Jung,
Jeong-Kuk Kim,
Ki Yong Nam,
Kyung-Zoo Lee,
Sung-Key Lee,
Wang Bong Park,
Myung-Suk Ko,
Won-Il Kim,
Byung-Kug Kim,
Byung Soo Kim,
Young Chan Jeon,
In Kyo Chung, Moon Kyoung Bae,
Hye-Ock Jang,
Il Yun
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[hide abstract]
ABSTRACT: The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of dopamine.HCl (DA) and chlorpromazin.HCl (CPZ). Radiationless energy transfer from the surface fluorescent probe, 1-anilinonaphthalene-8-sulfonic acid, to the hydrophobic fluorescent probe, bispyrenylpropane (Py-Py), was used to examine the effects of DA and CPZ on the thickness (D) of the liposomal lipid bilayers prepared with total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from neuronal membranes. The thickness (D) of intact SPMVTL and SPMVPL (37 degrees C, pH 7.4) were 0.914 +/- 0.010 and 0.886 +/- 0.009 (arbitrary units, n = 5), respectively. DA decreased the thickness of both SPMVTL and SPMVPL in a dose-dependent manner with a significant decrease in thickness observed even at 40 x 10(-9) M and 40 x 10(-9) M, respectively. On the other hand, CPZ increased the thickness of both SPMVTL and SPMVPL in a dose-dependent manner with a significant increase in thickness observed even at 35 x 10(-5) M and 35 x 10(-5) M, respectively. The sensitivities to the decreasing and increasing effect of the membrane lipid bilayers thickness by DA and CPZ, respectively, differed according to the liposomes in descending order of SPMVPL and SPMVTL. The decreasing and increasing action of DA and CPZ, respectively, on the membrane thickness had many effects that may be responsible for the dopaminergic receptor-DA and -CPZ interaction as well as the protein-lipid interaction.
Archives of Pharmacal Research 05/2010; 33(5):737-44. · 1.59 Impact Factor
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Young-Sik Park,
No-Soo Park,
Jun-Bong Seo,
Soo-Kyoung Bae,
You-Kwang Kim,
Ki-Soo Seong,
Young-Jun Kim,
Ju-Won Park,
Joung-Moung Shin,
Young-Chan Jeon,
In-Kyo Chung, Moon-Kyoung Bae,
Hye-Ock Jang,
Il Yun
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ABSTRACT: The aim of this study was to provide a basis for examining the molecular mechanism for the pharmacological action of ethanol. We studied di-myristoylphosphatidylethanol (DMPEt)'s effects on specific locations of n-(9-anthroyloxy) palmitic acid or stearic acid (n-AS) within phospholipids of synaptosomal plasma membrane vesicles isolated from bovine cerebral cortex (SPMV) and liposomes of total lipids (SPMVTL) and phospholipids (SPMVPL) extracted from SPMV. DMPEt increased rotational mobility (increased disordering) of hydrocarbon interior, but it de-creased mobility (increased ordering) of mem-brane interface, in native and model membranes. The degree of rotational mobility in accordance with the carbon atom numbers of phospholipids comprising neuronal membranes was in the order at the 16, 12, 9, 6 and 2 position of ali-phatic chain present in phospholipids. The sensitivity of increasing or decreasing effect of rotational mobility of hydrocarbon interior or surface region by DMPEt differed depending on the neuronal and model membranes in the de-scending order of SPMV, SPMVPL and SPMVTL.
Journal of Biophysical Chemistry. 01/2010; 1:133-140.
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Hyun-Joo Park,
Su-Ryun Kim,
Soo-Kyung Bae,
Yoon Kyung Choi,
Yun-Hee Bae,
Eok-Cheon Kim,
Woo Jean Kim,
Hye-Ock Jang,
Il Yun,
Young-Myeong Kim, Moon-Kyoung Bae
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ABSTRACT: Neuromedin B (NMB) is one of the bombesin-like peptides in mammals. Recently, bombesin-like peptides have been characterized as growth factors in highly vascularized tumors. In this study, we report that NMB potently stimulates in vivo neovascularization in a mouse Matrigel plug and the sprouting of endothelial cells ex vivo in rat aortic rings. In addition, NMB increases the migration and tube formation in human umbilical vein endothelial cells (HUVECs). Moreover, treatment of HUVECs with NMB activates the extracellular signal-regulated kinase 1/2 (ERK(1/2)), Akt, and endothelial nitric oxide synthase (eNOS) and increases the level of NO production in a dose- and time-dependent manner. Furthermore, ERK activation and angiogenic sprouting in response to NMB are significantly blocked by the MEK inhibitor. Inhibition of phosphatidylinositol 3-kinase (PI3K) suppresses the NMB-stimulated tubular formation of HUVECs, along with reduction in the phosphorylation of Akt and eNOS. Taken together, these results indicate that NMB is a novel angiogenic peptide, and its angiogenic activity is mediated by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent pathways. This study suggests that NMB may play important roles in mediating a variety of pathophysiological angiogenesis.
Experimental Cell Research 09/2009; 315(19):3359-69. · 3.58 Impact Factor
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ABSTRACT: Signal transducer and activator of transcription 3 (STAT3) acts as a mediator and biomarker in endothelial activation. We have recently shown that a novel adipokine visfatin promotes endothelial angiogenesis. The present study was to determine whether visfatin affects STAT3 activity and to explore the potential target gene(s). Here, we found that visfatin induced the activation of STAT3, as characterized by increased tyrosine phosphorylation, nuclear translocation, and DNA-binding activity in human endothelial cells. In addition, visfatin significantly upregulated mRNA and protein levels of endothelial interleukin-6 (IL-6), which was blocked by a specific inhibitor of STAT3 signaling and by the transfection of siRNA specific for STAT3. Furthermore, visfatin-induced angiogenesis was reduced by the inhibition of STAT3 signaling or neutralization of IL-6 function, as measured by tube formation, rat aortic ring assay, and mouse Matrigel plug assay. Taken together, our results provide the first example of STAT3-dependent endothelial IL-6 induction by visfatin and of the role of IL-6 in mediating visfatin-induced angiogenesis.
Biochimica et Biophysica Acta 09/2009; 1793(11):1759-67. · 4.66 Impact Factor
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ABSTRACT: Aspirin has been reported to induce apoptosis in various cancer cell lines. However, the apoptotic effects of aspirin on human brain tumor cells are not well understood. Here, we have assessed the effect of aspirin on human gliobalstoma cell line A172 and found that aspirin induced the apoptosis of A172 cells, as determined by TUNEL assay, FACS analysis, and Hoechst staining. The underlying mechanism of this effect consists of reduction in the level of phosphorylated STAT3 (Tyr705), a transcription factor required for survival of A172 cells. Moreover, the expression of STAT3 target genes such as Cyclin D1, XIAP, and Bcl-2 that are essential for cell growth and survival was apparently attenuated after aspirin treatment. We also showed that the expression and secretion of interleukin-6 (IL-6), leading to STAT3 phosphorylation, was inhibited by aspirin. When administered exogenous IL-6 to aspirin-treated A172 cells, the phosphorylation of STAT3 and cellular apoptosis were restrained compared to aspirin only-treated cells. Taken together, our results indicate that aspirin causes apoptosis via down-regulation of IL-6-dependent STAT3 signaling, suggesting that aspirin could be therapeutically useful for a potential anti-glioblastoma therapeutic approach.
Biochemical and Biophysical Research Communications 08/2009; 387(2):342-7. · 2.48 Impact Factor
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Hyun-Joo Park,
Seong-Kyoon Jeong,
Su-Ryun Kim,
Soo-Kyung Bae,
Woo-Sik Kim,
Seong-Deok Jin,
Tae Hyeon Koo,
Hye-Ock Jang,
Il Yun,
Kyu-Won Kim, Moon-Kyoung Bae
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ABSTRACT: P. gingivalis is a major pathogen that is involved in the onset and progression of periodontal disease. This study investigated the effect of resveratrol, a naturally occurring polyphenol, on P. gingivalis LPS-accelerated vascular inflammation, a key step in the progression of periodontitis. Resveratrol significantly inhibited the P. gingivalis LPS-induced adhesion of leukocytes to endothelial cells and to the aortic endothelium by down-regulating the cell adhesion molecules, ICAM-1 and VCAM-1. Moreover, the inhibition of the P. gingivalis LPS-induced cell adhesion molecules by resveratrol was mainly mediated by nuclear factor-kappaB (NF-kappaB). Resveratrol suppressed P. gingivalis LPS-stimulated IkappaBalpha phosphorylation and nuclear translocation of the p65 subunit of NF-kappaB in HMECs. Overall, these findings suggest that resveratrol significantly attenuates the P. gingivalis LPS-induced monocyte adhesion to the endothelium by suppressing the expression of the NF-kappaB-dependent cell adhesion molecules, suggesting its therapeutic role in periodontal pathogen-induced vascular inflammation.
Archives of Pharmacal Research 05/2009; 32(4):583-91. · 1.59 Impact Factor
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ABSTRACT: Porphyromonas gingivalis, a major periodontal pathogen, has been implicated in the initiation and progression of periodontal disease. Endothelial dysfunction (Editor note: Aberrant and dysfunction are somewhat redundant. The authors may want to choose one or the other.) contributes to chronic periodontal inflammation. Using cDNA-represen-tational difference analysis, we found that P.gingivalis lipopolysaccharide differentially induces a number of genes in human microvascular endothelial cells. Among these upregulated genes, we focused on intercellular adhesion molecule-1 (VCAM-1), which is crucial for leukocyte recruitment during vascular inflammation. P. gingivalis LPS significantly increased the expression of vascular cell adhesion molecule-1 (VCAM-1) as well as ICAM-1. Promoter assays revealed that the transcription of these cell adhesion molecules was mainly regulated by nuclear factor-κB (NF-κB) in endothelial cells. Furthermore, P. gingivalis LPS significantly increased leukocyte adhesiveness to microvascular endothelial cells and to aortic endothelium. Taken together, our results demonstrate that P. gingivalis LPS activates microvascular endothelial cells through NF-κB-dependent expression of cell adhesion molecules.
International Journal of Oral Biology The Korean Academy of Oral Biology International Journal of Oral Biology. 01/2009; 33(149).
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ABSTRACT: Drosophila big brain (bib) encodes for a protein similar to members of the major intrinsic protein family, which includes the water- and ion-conducting aquaporin (AQP) channels. In mammals, AQP dysregulation has been implicated in a variety of diseases, including colorectal cancer and colonic injury. However, the regulatory mechanisms of AQP expression remain to be clearly elucidated. In this study, as we found a DREF binding site (DRE) in the 5'-flanking regions of both the Drosophila bib gene and the human AQP1 gene, we assessed the role of DREF in bib gene expression. DREF in Drosophila and humans has been demonstrated to function as a key transcriptional activator for cell proliferation-related genes. Herein, we demonstrate that the DRE is required for optimal promoter activity of Drosophila bib gene, particularly in the larval imaginal discs, which are actively proliferating tissues, as well as the adult hindgut. Our results may provide insight into the mechanisms inherent to the regulation of mammalian AQP genes.
Biochimica et Biophysica Acta 09/2008; 1779(12):789-96. · 4.66 Impact Factor
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Su-Ryun Kim,
Yun-Hee Bae,
Soo-Kyung Bae,
Kyu-Sil Choi,
Kwon-Ha Yoon,
Tae Hyeon Koo,
Hye-Ock Jang,
Il Yun,
Kyu-Won Kim,
Young-Guen Kwon,
Mi-Ae Yoo, Moon-Kyoung Bae
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ABSTRACT: Visfatin has recently been identified as a novel visceral adipokine which may be involved in obesity-related vascular disorders. However, it is not known whether visfatin directly contributes to endothelial dysfunction. Here, we investigated the effect of visfatin on vascular inflammation, a key step in a variety of vascular diseases. Visfatin induced leukocyte adhesion to endothelial cells and the aortic endothelium by induction of the cell adhesion molecules, ICAM-1 and VCAM-1. Promoter analysis revealed that visfatin-mediated induction of CAMs is mainly regulated by nuclear factor-kappaB (NF-kappaB). Visfatin stimulated IkappaBalpha phosphorylation, nuclear translocation of the p65 subunit of NF-kappaB, and NF-kappaB DNA binding activity in HMECs. Furthermore, visfatin increased ROS generation, and visfatin-induced CAMs expression and NF-kappaB activation were abrogated in the presence of the direct scavenger of ROS. Taken together, our results demonstrate that visfatin is a vascular inflammatory molecule that increases expression of the inflammatory CAMs, ICAM-1 and VCAM-1, through ROS-dependent NF-kappaB activation in endothelial cells.
Biochimica et Biophysica Acta 06/2008; 1783(5):886-95. · 4.66 Impact Factor
