Myung-Kwan Han

Chonbuk National University Hospital, Sŏul, Seoul, South Korea

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Publications (47)208.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: NAD glycohydrolases (NADases) catalyze the hydrolysis of NAD to ADP-ribose and nicotinamide. Although many members of the NADase family, including ADP-ribosyltransferases (ART), have been cloned and characterized, the structure and function of NADases with pure hydrolytic activity remain to be elucidated. Here, we report the structural and functional characterization of a novel NADase from rabbit reticulocytes. The novel NADase is a glycosylated, GPI-anchored cell surface protein, exclusively expressed in reticulocytes. shRNA-mediated knock-down of the NADase in bone marrow cells resulted in a reduction of erythroid colony formation and an increase in NAD level. Furthermore, treatment of bone marrow cells with NAD, nicotinamide or nicotinamide riboside, which induce an increase in NAD content, resulted in a significant decrease in erythroid progenitors. These results indicate that the novel NADase may play a critical role in regulating erythropoiesis of hematopoietic stem cells through modulating intracellular NAD.
    Journal of Biological Chemistry 04/2014; · 4.65 Impact Factor
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    ABSTRACT: SIRT1 modulates the acetylation of the p65 subunit of nuclear factor-κB (NF-κB) and plays a pivotal role in the inflammatory response. This study sought to assess the role of SIRT1 in rheumatoid arthritis (RA) using a myeloid cell-specific SIRT1 knockout (mSIRT1 KO) mouse. mSIRT1 KO mice were generated using the loxP/Cre recombinase system. K/BxN serum transfer arthritis was induced in mSIRT1 KO mice and age-matched littermate loxP control mice. Arthritis severity was assessed by clinical and pathological scoring. The levels of inflammatory cytokines in the serum and joints were measured by ELISA. Migration, M1 polarization, cytokine production, osteoclastogenesis, and p65 acetylation were assessed in bone marrow-derived monocytes/macrophages (BMMs). mSIRT1 KO mice showed more severe inflammatory arthritis and aggravated pathological findings than control mice. These effects were paralleled by increases in IL-1, TNF-α, TRAP-positive osteoclasts, and F4/80(+) macrophages in the ankles of mSIRT1 KO mice. In addition, BMMs from mSIRT1 KO mice displayed hyperacetylated p65 and increased NF-κB binding activity when compared to control mice, which resulted in increased M1 polarization, migration, pro-inflammatory cytokine production, and osteoclastogenesis. Our study provides in vivo evidence that myeloid cell-specific deletion of SIRT1 exacerbates inflammatory arthritis via the hyperactivation of NF-κB signaling, which suggests that SIRT1 activation may be beneficial in the treatment of inflammatory arthritis.
    PLoS ONE 01/2014; 9(2):e87733. · 3.73 Impact Factor
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    ABSTRACT: Lipopolysaccharide (LPS), an endotoxin derived from gram-negative bacteria, promotes the secretion of proinflammatory cytokines and mediates endotoxemia through activation of mitogen activated protein kinases, NF-κB, and interferon regulatory factor-3. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, mediates NF-κB deacetylation, and inhibits its function. SIRT1 may affect LPS-mediated signaling pathways and endotoxemia. Here we demonstrate that SIRT1 blocks LPS-induced secretion of interleukin 6 and tumor necrosis factor α in murine macrophages, and protects against lethal endotoxic and septic shock in mice. We also demonstrate that interferon β increases SIRT1 expression by activating the Janus kinase - signal transducer and activator of transcription (JAK-STAT) pathway in mouse bone marrow derived macrophages. In vivo treatment of interferon β protects against lethal endotoxic and septic shock, which is abrogated by infection with dominant negative SIRT1-expressing adenovirus. Our work suggests that both SIRT1 and SIRT1-inducing cytokines are useful targets for treating patients with sepsis.
    Scientific Reports 01/2014; 4:4220. · 5.08 Impact Factor
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    ABSTRACT: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger for mobilizing Ca2+ from intracellular stores in various cell types. Extracellular application of NAADP has been shown to elicit intracellular Ca2+ signals, indicating that it is readily transported into cells. However, little is known about the functional role of this NAADP-uptake system. Here, we show that NAADP is effectively transported into selected cell types involved in glucose homeostasis, such as adipocytes and pancreatic β cells, but not the acinar cells, in a high glucose-dependent manner. NAADP uptake was inhibitable by Ned-19, a NAADP mimic, dipyridamole, a nucleoside inhibitor, NaN3, a metabolic inhibitor or under Ca2+-free condition. Furthermore, NAADP was found to be released from pancreatic islets upon stimulation by high glucose. Consistently, administration of NAADP to type 2 diabetic mice improved glucose tolerance. We propose that NAADP is functioning as an autocrine/paracrine hormone important in glucose homeostasis. NAADP is thus a potential anti-diabetic agent with therapeutic relevance.
    Journal of Biological Chemistry 10/2013; · 4.65 Impact Factor
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    ABSTRACT: Cross-talk between intracellular signaling pathways has been extensively studied to understand the pluripotency of human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs); however, the contribution of NAD(+) -dependent pathways remains largely unknown. Here, we show that NAD(+) depletion by FK866 (a potent inhibitor of NAD(+) biosynthesis) was fatal in hPSCs, particularly when deriving pluripotent cells from somatic cells and maintaining pluripotency. NAD and its precursors (nicotinamide (NAM) and nicotinic acid (NA)) fully replenished the NAD(+) depletion by FK866 in hPSCs. However, only NAM effectively enhanced the reprogramming efficiency and kinetics of hiPSC generation and was also significantly advantageous for the maintenance of undifferentiated hPSCs. Our molecular and functional studies reveal that NAM lowers the barriers to reprogramming by accelerating cell proliferation and protecting cells from apoptosis and senescence by alleviating oxidative stress, reactive oxygen species (ROS) accumulation, and subsequent mitochondrial membrane potential collapse. We provide evidence that the positive effects of NAM (occurring at concentrations well above the physiological range) on pluripotency control are molecularly associated with the repression of p53, p21, and p16. Our findings establish that adequate intracellular NAD(+) content is crucial for pluripotency; the distinct effects of NAM on pluripotency may be dependent not only on its metabolic advantage as a NAD(+) precursor but also on the ability of NAM to enhance resistance to cellular stress.
    Stem Cells 03/2013; · 7.70 Impact Factor
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    ABSTRACT: CD38, an ADP ribosyl cyclase, is a 45 kDa type II transmembrane protein having a short N-terminal cytoplasmic domain and a long C-terminal extracellular domain, expressed on the surface of various cells including macrophages, lymphocytes, and pancreatic β cells. It is known to be involved in cell adhesion, signal transduction and calcium signaling. In addition to its transmembrane form, CD38 is detectable in biological fluids in soluble forms. The mechanism by which CD38 is solubilized from the plasma membrane is not yet clarified. In this study, we found that lipopolysaccharide (LPS) induced CD38 upregulation and its extracellular release in J774 macrophage cells. Furthermore, it also increased CD38 expression at the mRNA level by activating the Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway. However, LPS decreased the levels of CD38 in the plasma membrane by releasing CD38 into the culture supernatant. LPS-induced CD38 release was blocked by the metalloproteinase-9 inhibitor indicating that MMP-9 solubilizes CD38. In conclusion, the present findings demonstrate a potential mechanism by which C38 is solubilized from the plasma membrane.
    Molecules and Cells 11/2012; · 2.21 Impact Factor
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    ABSTRACT: Insulin stimulates glucose uptake through the membrane translocation of GLUT4 and GLUT1. Peroxisome proliferator-activated receptor γ (PPARγ) enhances insulin sensitivity. Here, we demonstrate that insulin stimulates GLUT4 and GLUT1 translocation, and glucose uptake, by activating the signaling pathway involving nicotinic acid adenine dinucleotide phosphate (NAADP), a calcium mobilizer, in adipocytes. We also demonstrate that PPARγ mediates insulin sensitization by enhancing NAADP production through upregulation of CD38, the only enzyme identified for NAADP synthesis. Insulin produced NAADP by both CD38-dependent and -independent pathways, whereas PPARγ produced NAADP by CD38-dependent pathway. Blocking the NAADP signaling pathway abrogated both insulin-stimulated and PPARγ-induced GLUT4 and GLUT1 translocation, thereby inhibiting glucose uptake. CD38 knockout partially inhibited insulin-stimulated glucose uptake. However, CD38 knockout completely blocked PPARγ-induced glucose uptake in adipocytes and PPARγ-mediated amelioration of glucose tolerance in diabetic mice. These results demonstrated that the NAADP signaling pathway is a critical molecular target for PPARγ-mediated insulin sensitization.
    Cell Reports 11/2012; · 7.21 Impact Factor
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    ABSTRACT: SIRT1, a histone diacetylase, modify transactivation function of various transcription factor including p53 and NF-κB. p53 and NF-κB is involved in in vitro differentiation of mouse embryonic stem cells (mESC) into mouse embryoid body (mEB). These suggest that SIRT1 might affect in vitro differentiation of mESC into mEB by regulation of p53 and NF-κB. In this study we analyzed the effect of SIRT1 in in vitro differentiation of mESC into mEB using wild and SIRT1 knockout mESC. To examine SIRT1-specific gene in mESC, this study conducted microarray-based differential gene expression analysis between wild and SIRT1 knockout mESC. Comparing their gene expression patterns, this study determined a list of genes regulated by SIRT1. cDNA microarray data-set analysis revealed that genes associated with transcription and signal transduction are significantly modified in SIRT1 knockout mESC. cDNA microarray data-set analysis between mESC and EB in wild and SIRT1 showed that SIRT1 inhibits p53 signaling pathway but not affect NF-κB signaling pathway. This study suggests that SIRT1 modify mESC differentiation by regulation of p53 transcriptional activity.
    International journal of stem cells. 11/2012; 5(2):125-129.
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    ABSTRACT: Phagocytosis is a crucial event in the immune system that allows cells to engulf and eliminate pathogens. This is mediated through the action of immunoglobulin (IgG)-opsonized microbes acting on Fcγ receptors (FcγR) on macrophages, which results in sustained levels of intracellular Ca(2+) through the mobilization of Ca(2+) second messengers. It is known that the ADP-ribosyl cyclase is responsible for the rise in Ca(2+) levels after FcγR activation. However, it is unclear whether and how CD38 is involved in FcγR-mediated phagocytosis. Here we show that CD38 is recruited to the forming phagosomes during phagocytosis of IgG-opsonized particles and produces cyclic-ADP-ribose, which acts on ER Ca(2+) stores, thus allowing an increase in FcγR activation-mediated phagocytosis. Ca(2+) data show that pretreatment of J774A.1 macrophages with 8-bromo-cADPR, ryanodine, blebbistatin, and various store-operated Ca(2+) inhibitors prevented the long-lasting Ca(2+) signal, which significantly reduced the number of ingested opsonized particles. Ex vivo data with macrophages extracted from CD38(-/-) mice also shows a reduced Ca(2+) signaling and phagocytic index. Furthermore, a significantly reduced phagocytic index of Mycobacterium bovis BCG was shown in macrophages from CD38(-/-) mice in vivo. This study suggests a crucial role of CD38 in FcγR-mediated phagocytosis through its recruitment to the phagosome and mobilization of cADPR-induced intracellular Ca(2+) and store-operated extracellular Ca(2+) influx.
    Journal of Biological Chemistry 03/2012; 287(18):14502-14. · 4.65 Impact Factor
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    ABSTRACT: Dendroaspis natriuretic peptide (DNP), a new member of the natriuretic peptide family, is structurally similar to atrial, brain, and C-type natriuretic peptides. However, the effects of DNP on the cardiac function are poorly defined. In the present study, we examined the effect of DNP on the cardiac L-type Ca(2+) channels in rabbit ventricular myocytes. DNP inhibited the L-type Ca(2+) current (I(Ca,L)) in a concentration dependent manner with a IC(50) of 25.5 nM, which was blocked by an inhibitor of protein kinase G (PKG), KT5823 (1 μM). DNP did not affect the voltage dependence of activation and inactivation of I(Ca,L). The α(1c) subunit of cardiac L-type Ca(2+) channel proteins was phosphorylated by the treatment of DNP (1 μM), which was completely blocked by KT5823 (1 μM). Finally, DNP also caused the shortening of action potential duration in rabbit ventricular tissue by 22.3 ± 4.2% of the control (n = 6), which was completely blocked by KT5823 (1 μM). These results clearly indicate that DNP inhibits the L-type Ca(2+) channel activity by phosphorylating the Ca(2+) channel protein via PKG activation.
    Experimental and Molecular Medicine 02/2012; 44(6):363-8. · 2.57 Impact Factor
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    ABSTRACT: The downstream of kinase (DOK)-1 is involved in the protein tyrosine kinase (PTK) pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.
    PLoS ONE 01/2012; 7(4):e34554. · 3.73 Impact Factor
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    ABSTRACT: The ADP-ribosyl cyclase CD38 whose catalytic domain resides in outside of the cell surface produces the second messenger cyclic ADP-ribose (cADPR) from NAD(+). cADPR increases intracellular Ca(2+) through the intracellular ryanodine receptor/Ca(2+) release channel (RyR). It has been known that intracellular NAD(+) approaches ecto-CD38 via its export by connexin (Cx43) hemichannels, a component of gap junctions. However, it is unclear how cADPR extracellularly generated by ecto-CD38 approaches intracellular RyR although CD38 itself or nucleoside transporter has been proposed to import cADPR. Moreover, it has been unknown what physiological stimulation can trigger Cx43-mediated export of NAD(+). Here we demonstrate that Cx43 hemichannels, but not CD38, import cADPR to increase intracellular calcium through RyR. We also demonstrate that physiological stimulation such as Fcγ receptor (FcγR) ligation induces calcium mobilization through three sequential steps, Cx43-mediated NAD(+) export, CD38-mediated generation of cADPR and Cx43-mediated cADPR import in J774 cells. Protein kinase A (PKA) activation also induced calcium mobilization in the same way as FcγR stimulation. FcγR stimulation-induced calcium mobilization was blocked by PKA inhibition, indicating that PKA is a linker between FcγR stimulation and NAD(+)/cADPR transport. Cx43 knockdown blocked extracellular cADPR import and extracellular cADPR-induced calcium mobilization in J774 cells. Cx43 overexpression in Cx43-negative cells conferred extracellular cADPR-induced calcium mobilization by the mediation of cADPR import. Our data suggest that Cx43 has a dual function exporting NAD(+) and importing cADPR into the cell to activate intracellular calcium mobilization.
    Journal of Biological Chemistry 12/2011; 286(52):44480-90. · 4.65 Impact Factor
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    ABSTRACT: Platelet-activating factor (PAF) is a major mediator in the induction of fatal hypovolemic shock in murine anaphylaxis. This PAF-mediated effect has been reported to be associated with PI3K/Akt-dependent eNOS-derived NO. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is phosphatidylinositol phosphate phosphatase, which negatively controls PI3K by dephosphorylating the signaling lipid, phosphatidylinositol 3,4,5-triphosphate. In this study, we examined the possible involvement of PTEN in PAF-mediated anaphylactic shock. Induction of anaphylaxis or PAF injection resulted in a rapid decrease in PTEN activity, followed by increases in PI3K activity and phosphorylation of Akt and eNOS. Systemic administration of adenoviruses carrying PTEN cDNA (adenoviral PTEN), but not the control AdLacZ, not only attenuated anaphylactic symptoms, but also reversed anaphylaxis- or PAF-induced changes in PTEN and PI3K activities, as well as phosphorylation of Akt and eNOS. We found that the decreased PTEN activity was associated with PTEN phosphorylation, the latter effect being prevented by the protein kinase CK2 inhibitor, DMAT. DMAT also inhibited anaphylactic symptoms as well as the anaphylaxis- or PAF-mediated PTEN/PI3K/Akt/eNOS signaling cascade. CK2 activity was increased by PAF. The present data provide, as the key mechanism underlying anaphylactic shock, PAF triggers the upstream pathway CK2/PTEN, which ultimately leads to the activation of PI3K/Akt/eNOS. Therefore, CK2/PTEN may be a potent target in the control of anaphylaxis and other many PAF-mediated pathologic conditions.
    The Journal of Immunology 06/2011; 186(11):6625-32. · 5.52 Impact Factor
  • Journal of Tissue Engineering and Regenerative Medicine 01/2011; 8(No.2):224-229. · 4.43 Impact Factor
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    ABSTRACT: Iron deficiency is a common nutritional problem and results in anemia in human population. Heme iron (HI) is known to be a better iron supplement than non-HI because of its fewer gastrointestinal side effects. HI polypeptide (HIP) is prepared by enzymatic digestion of hemoglobin from animal blood and subsequent ultrafiltration or dialysis. Here we find a polymerized form of HIP with high iron content and provide an efficient method to prepare the HIP polymer. The molecular weight of the HIP polymer was around 250 kDa, which was determined by gel filtration. The polymer was soluble in a wide range of pH, and iron content was about 1.8%, that is the highest among any other forms of HIP. Moreover, when administered to healthy human, the polymer increased serum iron level twofold, 5 h after the administration. These data indicate that the HIP polymer containing high level of iron can be used as an ideal iron supplement in anemic patients.PRACTICAL APPLICATIONSHeme iron polypeptide (HIP) is an ideal iron supplement because of its good solubility and absorption while being less toxic to gastrointestinal cells. However, there are few reports on preparations of HIP from animal whole blood as a food supplement. The present study reports preparation and characterization of HIP polymer containing high level of iron from porcine blood. It is beneficial to utilize porcine whole blood, which is abundantly available at a low price. Therefore, it would provide a useful technique for mass production of the ideal iron supplement.
    Journal of Food Biochemistry 05/2010; 34(4):896 - 904. · 0.76 Impact Factor
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    ABSTRACT: Endothelial hyperpermeability, a hallmark of septicemia, is induced by stress fiber formation, which is primarily regulated by the calcium/calmodulin signaling pathway in endothelial cells. We previously reported that trifluoperazine, a calcium/calmodulin antagonist, blocks Vibrio vulnificus cytolysin (VVC) -induced lethality at in vivo animal model. The object of this study was therefore to examine whether VVC induces stress fiber formation through calcium/calmodulin signaling in endothelial cells. Here, we monitored calcium-influx after treatment of VVC using confocal microscopy in CPAE cells, pulmonary endothelial cell line. Interestingly, we found that VVC-induced dose-dependently increases of [Ca(2+)](i) in CPAE cells. Moreover, VVC-induced stress fiber formation as well as phosphorylation of myosin light chain (MLC) in a dose- and time-dependent manner, which was completely blocked by trifluoperazine. These results suggest that the calcium/calmodulin signaling pathway plays a pivotal role in VVC-induced hyperpermeability.
    Microbial Pathogenesis 06/2009; 47(1):47-51. · 1.97 Impact Factor
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    ABSTRACT: SIRT1, a class III histone/protein deacetylase, is known to interfere with the nuclear factor-kappaB (NF-kappaB) signaling pathway and thereby has an anti-inflammatory function. Because of the central role of NF-kappaB in cytokine-mediated pancreatic beta-cell damage, we postulated that SIRT1 might work in pancreatic beta-cell damage models. RINm5F (RIN) cells or isolated rat islets were treated with interleukin-1beta and interferon-gamma. SIRT1 was activated by resveratrol, a pharmacological activator, or ectopic overexpression. The underlying mechanisms of SIRT1 against cytokine toxicity were further explored. Treatment of RIN cells with cytokines induced cell damage, and this damage was well correlated with the expression of the inducible form of nitric oxide (NO) synthase (iNOS) and NO production. However, SIRT1 overexpression completely prevented cytokine-mediated cytotoxicity, NO production, and iNOS expression. The molecular mechanism by which SIRT1 inhibits iNOS expression appeared to involve the inhibition of the NF-kappaB signaling pathway through deacetylation of p65. In addition, SIRT1 activation by either resveratrol or adenoviral-directed overexpression of SIRT1 could prevent cytokine toxicity and maintain normal insulin-secreting responses to glucose in isolated rat islets. This study will provide valuable information not only into the mechanisms underlying beta-cell destruction but also into the regulation of SIRT1 as a possible target to attenuate cytokine-induced beta-cell damage.
    Diabetes 12/2008; 58(2):344-51. · 7.90 Impact Factor
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    ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been identified as a potential source of therapy for human cancers. However, PPARgamma ligands have a limitation for breast cancer therapy, since estrogen receptor alpha (ER(alpha)) negatively interferes with PPARgamma signaling in breast cancer cells. Here we show that ER(alpha) inhihits PPARgamma transactivity and ER(alpha)-mediated inhibition of PPARgamma transactivity is blocked by tamoxifen, an estrogen receptor blocker. The activation of ER(alpha) with 17-beta-estradiol blocked PPRE transactivity induced by troglitazone, a PPARgamma ligand, indicating the resistance of ER(alpha)-positive breast cancer cells to troglitazone. Indeed, troglitazone inhibited the growth of ER(alpha)-negative MDA-MB-231 cells more than that of ER(alpha)-positive MCF-7 cells. Combination of troglitazone with tamoxifen led to a marked increase in growth inhibition of ER(alpha)-positive MCF-7 cells compared to either agent alone. Our data indicates that troglitazone enhances the growth inhibitory activity of tamoxifen in ER(alpha)-positive MCF-7 cells.
    Biochemical and Biophysical Research Communications 11/2008; 377(1):242-7. · 2.41 Impact Factor
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    ABSTRACT: Rheumatoid arthritis (RA) synovial fibroblasts produce matrix metaloproteinases (MMPs), which destroy cartilage and bone in RA joint. Tumor necrosis factor-alpha (TNF-alpha) is one of the most important mediator leading to MMP production in RA synovial fibroblasts. Here we show that epigallocatechin-3-Gallate (EGCG) suppresses TNF-alpha-induced production of MMP-1 and MMP-3 in RA synovial fibroblasts, which was accompanied by inhibition of mitogen activated protein kinase (MAPK) and activator protein-1 (AP-1) pathways. EGCG treatment resulted in dose-dependent inhibition of TNF-alpha-induced production of MMP-1 and MMP-3 at the protein and mRNA levels in RA synovial fibroblast. EGCG treatment also inhibited TNF-alpha-induced phosphorylation of MAPKs, such as ERK1/2, p38, JNK. Electrophoretic mobility shift assay revealed that EGCG inhibits binding of AP-1 proteins to its response elements in synovial fibroblast treated. Thus, EGCG may play a role in regulating inflammation and bone destruction in RA patients.
    Rheumatology International 06/2008; 29(1):23-9. · 2.21 Impact Factor
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    ABSTRACT: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands inhibit cell proliferation and induce apoptosis in cancer cells. Here we wished to determine whether the PPARgamma ligand induces apoptosis and cell cycle arrest of the MDA-MB-231 cell, an estrogen receptor alpha negative breast cancer cell line. The treatment of MDA-MB-231 cell with PPARgamma ligands was shown to induce inhibition of cell growth in a dose-dependent manner as determined by MTT assay. Cell cycle analysis showed a G1 arrest in MDA-MB-231 cells exposed to troglitazone. An apoptotic effect by troglitazone demonstrated that apoptotic cells elevated by 2.5-fold from the control level at 10 microM, to 3.1-fold at 50 microM and to 3.5-fold at 75 microM. Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in pRb, cyclin D1, cyclin D2, cyclin D3, Cdk2, Cdk4 and Cdk6 expression as well as a significant increase in p21 and p27 expression. These results indicate that troglitazone causes growth inhibition, G1 arrest and apoptotic death of MDA-MB-231 cells.
    Cell Biology International 05/2008; 32(8):906-12. · 1.64 Impact Factor

Publication Stats

732 Citations
208.85 Total Impact Points

Institutions

  • 2000–2013
    • Chonbuk National University Hospital
      Sŏul, Seoul, South Korea
  • 2012
    • Wonkwang University School of Medicine and Hospital
      Riri, North Jeolla, South Korea
  • 2007–2008
    • Indiana University-Purdue University Indianapolis
      • Department of Microbiology and Immunology
      Indianapolis, IN, United States
  • 2003–2006
    • Chonbuk National University
      • School of Medicine
      Tsiuentcheou, North Jeolla, South Korea