Jin Tae Hong

Chungbuk National University, Chinsen, Chungcheongbuk-do, South Korea

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Publications (307)856.68 Total impact

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    ABSTRACT: Activation of nuclear factor kappa-B (NF-κB) is implicated in drug resistant of lung cancer cells. Our previous data showed that thiacremonone inhibited activation of NF-κB. In the present study, we investigated whether thiacremonone enhanced susceptibility of lung cancer cells to a common anti-cancer drug paclitaxel by further inhibition of NF-κB. Thus, we used the threefold lower doses of IC50 values (50 μg/ml thiacremonone and 2.5 nM paclitaxel). We found that combination treatment with thiacremonone and paclitaxel was more susceptible (combination index; 0.40 in NCI-H460 cells and 0.46 in A549 cells) in cell growth inhibition of two types of lung cancer cell lines compared to a single agent treatment. Consistent with the combination effect on cancer cell growth inhibition, the combination treatment further induced apoptotic cell death and arrested the cancer cells in G2/M phase accompanied with a much lower expression of cdc2 and cyclin B1, and inhibited colony formation. Much more inactivation of NF-κB and greater expression of NF-κB target apoptosis regulated genes such as caspase-8 and PARPs were found by the combination treatment. Molecular model and pull down assay as well as MALDI-TOF analysis demonstrated that thiacremonone directly binds to p50. These data indicated that thiacremonone leads to increased apoptotic cell death in lung cancer cell lines through greater inhibition of NF-κB by the combination treatment with paclitaxel.
    Archives of Pharmacal Research 03/2015; DOI:10.1007/s12272-015-0589-4 · 1.75 Impact Factor
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    ABSTRACT: Saururus chinensis is a medicinal plant used to treat jaundice, pneumonia, edema, fever, and several inflammatory diseases. Saucerneol D (SD), a lignan constituent of this plant, has antioxidant, anti-asthmatic, and anti-inflammatory activities. SD has been previously reported to inhibit the pro-inflammatory responses of RAW264.7 cells and primary mast cells. In this study, we investigated the effect of SD on the functions of dendritic cells (DCs). SD was isolated from methanol extract of the roots of S. chinensis. Bone marrow-derived DCs were used as target cells. The effects of SD on the following DC functions were examined: surface molecule expression, cytokine expression, migration, allogenic T cell activation, heme oxygenase-1 expression, and Toll-like receptor 4 signaling. In lipopolysaccharide (LPS)-treated DCs, SD inhibited the expression of cell surface molecules (MHC I/II, CD40, CD80, and CD86), the production of inflammatory mediators (nitric oxide, IL-12, IL-1β, and TNF-α), and allogenic T cell activation capacity. SD also inhibited DC migration toward MIP-3β by down-regulating CCR7 expression. SD attenuated LPS-induced activation of NF-κB and MAPK signaling in DCs, but did not directly inhibit kinase activities of IRAK1, IRAK4, TAK1, or IKKβ in enzymatic assays. SD did not inhibit LPS binding to myeloid differentiation protein-2, co-receptor of TLR4. SD increased the production of reactive oxygen species, Nrf-2, and heme oxygenase (HO)-1, which degrades the heme to immunosuppressive carbon monoxide and biliverdin, which may underlie the anti-inflammatory effects in SD-treated DCs. Taken together, these data suggest that SD suppresses LPS-induced activation of DCs through the induction of HO-1, but not by directly affecting Toll-like receptor 4 signaling. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Journal of ethnopharmacology 03/2015; DOI:10.1016/j.jep.2015.03.020 · 2.32 Impact Factor
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    ABSTRACT: Background and purpose cAMP as a second messenger stimulates expression of microphthalmia-associated transcription factor (MITF) or tyrosinase gene under ultraviolet B (UVB)-induced skin pigmentation. Diphenylmethylene hydrazinecarbothioamide (QNT 3-80) inhibits α-melanocyte-stimulating hormone (α-MSH)-induced melanin production in B16 murine melanoma cells but its molecular basis remains to be defined. Here, we investigated an antimelanogenic mechanism of QNT 3-80 in the amelioration of skin hyperpigmentation. Experimental approach cAMP-elevated melanocyte cultures were used for in vitro assays and UVB-irradiated dorsal skins of guinea pigs for in vivo pigmentation. Immunoprecipitation, kemptide phosphorylation, fluorescence analysis and docking simulation were applied to elucidate a molecular mechanism of QNT 3-80. Key results QNT 3-80 inhibited melanin production in vitro under cAMP-elevated melanocyte cultures including those from human foreskins, and also ameliorated hyperpigmentation in vivo under UVB-irradiated dorsal skins of guinea pigs. As a mechanism, QNT 3-80 directly antagonized cAMP binding to the regulatory subunit of protein kinase A (PKA), nullified the dissociation and activation of inactive PKA holoenzyme in melanocytes, and fitted into the cAMP-binding site on the crystal structure of human PKA under the most energetically favorable simulation. QNT 3-80 consequently inhibited cAMP- or UVB-induced phosphorylation (activation) of cAMP-responsive element (CRE)-binding protein (CREB) in vitro and in vivo, thus down-regulating expression of MITF or tyrosinase gene in the melanogenic process. Conclusions and Implications Taken together, this study suggests a significant implication of QNT 3-80 in the treatment of skin disorders with hyperpigmented patches via the cAMP-binding site of PKA as a molecular target. This article is protected by copyright. All rights reserved.
    British Journal of Pharmacology 03/2015; DOI:10.1111/bph.13134 · 5.07 Impact Factor
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    ABSTRACT: Two new iridoids, 6-O-[(E)-feruloyl]jioglutin D (1) and 6-O-(4-hydroxybenzoyl)jioglutin D (2), and six known compounds, minecoside (3), specioside (4), picroside II (5), picroside III (6), 4-hydroxybenzoic acid (7), and martynoside (8), were isolated from the stem of Catalpa ovata. The structures of the new compounds were established on the basis of spectroscopic techniques, including 1D- and 2D-NMR.
    Helvetica Chimica Acta 03/2015; 98(3). DOI:10.1002/hlca.201400203 · 1.39 Impact Factor
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    ABSTRACT: The aim of this study was to investigate the involvement of dopaminergic receptors (DR) in behavioral sensitization, as measured by locomotor activity, and the over-expression of cocaine- and amphetamine-regulated transcript (CART) peptides after repeated administration of cocaine in mice. Repeated administrations of cocaine induced behavioral sensitization and CART over-expression in mice. The levels of striatal CART mRNA were significantly increased on the 3(rd) day. CART peptides were over-expressed on the 5(th) day in the striata of behaviorally sensitized mice. A higher proportion of CART(+) cells in the cocaine-treated mice were present in the nucleus accumbens (NAc) shell than in the dorsolateral (DL) part of caudate putamen (CP). The concomitant administration of both D1R and D2R antagonists, SCH 23390 (D1R selective) and raclopride (D2R selective), blocked cocaine induced-behavioral sensitization, CART over-expression, and cyclic adenosine 5'-monophosphate (cAMP)/protein kinase A (PKA)/phospho-cAMP response element-binding protein (pCREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, pCREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both D1R and D2R knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/pCREB signal pathways were inhibited in the D1R-KO mice, but not in the D2R-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/pCREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by D1R.
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    ABSTRACT: Objective Chronic excessive food intake leads to energy imbalance, resulting in hepatic steatosis and inflammation. Interleukin-32 (IL-32) is known to be a pro-inflammatory cytokine associated with chronic inflammation and cancer. Therefore, the relationship between IL-32 and chronic excessive food intake-induced liver disease was investigated.Methods Male IL-32β transgenic and wild-type mice were fed a high-fat diet (HFD) for 15 weeks. They were compared with wild-type mice on a standard chow diet. Daily food intake, body and liver weight, serum biochemistry, histopathological analysis of the liver, and hepatic immune response were determined.ResultsIL-32β mice on HFD showed lower lipid accumulation, reduced infiltration of immune cells, and lower production of pro-inflammatory cytokines in the liver. The expression of the peroxisome proliferator-activated receptor γ (PPARγ) was downregulated and the adenosine 50-monophosphate (AMP)-activated protein kinase (AMPK) was activated in the liver of IL-32β mice compared to wild-type mice. Furthermore, IL-32β over-expression activated the AMPK pathway and IL-32β downregulation inactivated the AMPK pathway in HepG2 cells under high-glucose conditions.Conclusions These data suggest that IL-32β modulates lipid accumulation through inhibition of PPARγ expression and AMPK activation.
    Obesity 02/2015; DOI:10.1002/oby.21001 · 4.39 Impact Factor
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    ABSTRACT: Leptin, a hormone mainly produced from adipose tissue, has been shown to induce proliferation of cancer cells. However, the molecular mechanisms underlying leptin-induced tumor progression have not been clearly elucidated. In the present study, we investigated the role of autophagy in leptin-induced cancer cell proliferation using human hepatoma (HepG2) and breast cancer cells (MCF-7), and tumor growth in a xenograft model. Herein, we showed that leptin treatment caused autophagy induction as assessed by increase in expression of autophagy-related genes, including beclin-1, Atg5 and LC3 II, further induction of autophagosome formation and autophagic flux. Interestingly, inhibition of autophagic process by treatment with inhibitors and LC3B gene silencing blocked leptin-induced increase in cell number and suppression of apoptosis, indicating a crucial role of autophagy in leptin-induced tumor progression. Moreover, gene silencing of p53 or FoxO3A prevented leptin-induced LC3 II protein expression, suggesting an involvement of p53/FoxO3A axis in leptin-induced autophagy activation. Leptin administration also accelerated tumor growth in BALB/c nude mice, which was found to be autophagy dependent. Taken together, our results demonstrate that leptin-induced tumor growth is mediated by autophagy induction and autophagic process would be a promising target to regulate development of cancer caused by leptin production.
    Oncotarget 01/2015; · 6.63 Impact Factor
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    ABSTRACT: H9, a novel herbal extract, demonstrated cytotoxicity in A549 non-small cell lung cancer (NSCLC) cell lines. In this study, we investigated whether H9, and/or co-treatment with an anticancer drug, pemetrexed (PEM), inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. The mice were separated into groups and administered H9 and PEM for 2 weeks. Protein and mRNA levels were detected using western blotting and reverse transcription polymerase chain reaction (RT-PCR), respectively; immuno histochemistry (IHC) was also performed on the tumor tissues. H9 and co-treatment with PEM induced cleavages of pro-apoptotic factors, such as caspase-3, caspase-8, caspase-9, and poly ADP-ribose polymerase (PARP). Expression levels of cell-death receptors involving Fas/FasL, TNF-related apoptosis-inducing ligands (TRAIL), and TRAIL receptors were increased by H9 and co-treatment with PEM. Furthermore, analysis of levels of cell-cycle modulating proteins indicated that tumor cells were arrested in G1/S phase. In addition, phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)/Akt survival signaling pathways were inhibited by H9 and co-treatment with PEM. In conclusion, H9 and co-treatment with PEM inhibited tumor growth in BALB/c nude mice models bearing A549 NSCLC cells. These results indicate that H9 and co-treatment with PEM can be used as an anticancer therapy in NSCLC.
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    ABSTRACT: We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-κB) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1-5 μg/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-κB activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway.
    Oncotarget 01/2015; · 6.63 Impact Factor
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    ABSTRACT: Alcohol abuse and alcoholism lead to alcoholic liver disease, which is a major type of chronic liver disease worldwide. Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. However, the role of IL-32 in chronic liver disease has not been reported. Here, we tested the effect of IL-32γ on ethanol-induced liver injury in IL-32γ-overexpressing transgenic mice (IL-32γ mice) after chronic ethanol feeding. Male C57BL/6 and IL-32γ mice (10-12 weeks old) were fed a Lieber-DeCarli diet containing 6.6% ethanol for 6 weeks. IL-32γ-transfected HepG2 and Huh7 cells as well as primary hepatocytes from IL-32γ mice were treated with or without ethanol.The hepatic steatosis and damage induced by ethanol administration were attenuated in IL-32γ mice. Ethanol-induced Cytochrome P450 2E1 expression and hydrogen peroxide levels were decreased in the livers of IL-32γ mice, primary hepatocytes from IL-32γ mice and IL-32γ-overexpressing human hepatic cells. The ethanol-induced expression levels of cyclooxyganase-2 and interleukin-6 were reduced in the livers of IL-32γ mice. Because nuclear transcription factor kappa B (NF-κB) is a key redox transcription factor of inflammatory response, we examined NF-κB activity. Ethanol-induced NF-κB activities were significantly lower in the livers of IL-32γ mice than in wild-type mice. Furthermore, reduced infiltration of natural killer cells, cytotoxic T cells, and macrophages in the liver after ethanol administration was observed in the livers of IL-32γ mice. These data suggest that IL-32γ prevents ethanol-induced hepatic injury via the inhibition of oxidative damage and inflammatory responses.
    Clinical Science 01/2015; DOI:10.1042/CS20140576 · 5.63 Impact Factor
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    ABSTRACT: PRDX6 is a bifunctional protein with both glutathione peroxidase (GPx) and iPLA2 activities. Even though several pathophysiological functions have been studied, the definitive role of PRDX6 on tumor growth has been not clear. Here, we compared carcinogen-induced tumor growth in PRDX6 transgenic (Tg) mice and non Tg mice to evaluate roles of PRDX6 in lung tumor development. Urethane (1g/kg)-induced tumor incidence in PRDX6 Tg mice was significant higher compared to non Tg mice. In the tumors of PRDX6 Tg mice, the activation of JAK2/STAT3 and STAT3 DNA binding were also increased, which is accompanied with increased GPx and iPLA2 activities. PRDX6 was colocalized with JAK2 in tumor tissues and lung cancer cells, and also showed physical interaction with JAK2. We found that the increasing level of Prdx6 increases the activation of the JAK2/STAT3 pathway. Furthermore, PRDX6 Tg mice showed altered cytokine levels in the tumors, especially leading to increased CCL5 level. We validated that the activation of JAK2 was also decreased in lung tumors of CCR5(-/-) mice, and CCL5 increased the JAK2/STAT3 pathway in the lung cancer cells. Thus, our findings suggest that PRDX6 promotes lung tumor development via its mediated and CCL5 associated activation of the JAK2/STAT3 pathways. Copyright © 2015. Published by Elsevier Inc.
    Free Radical Biology and Medicine 01/2015; 80. DOI:10.1016/j.freeradbiomed.2014.12.022 · 5.71 Impact Factor
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    ABSTRACT: This experiment was designed to investigate whether 4-O-methylhonokiol (MH), a principal ingredient of Magnolia (M.) officinalis bark, alleviated acute intraperitoneal (i.p.) kainic acid- (KA-) induced brain blood barrier dysfunction (BBBD) via pathological examination and cytological analyses of the brain tissues of mice. KA (10-30 mg/kg) time- and dose-dependently increased the water content of brain tissues and induced edema and encephalopathy. However, pretreatment with MH (5 and 20 mg/kg, i.p.) significantly reduced the water content of the brain compared to that observed in the KA control group. Furthermore, MH significantly and dose-dependently reversed the remarkable variations in evan's blue dye (EBD) staining and malondialdehyde (MDA) levels that were induced by KA (10 mg/kg, i.p.). MH also decreased the elevated seizure scores that were induced by KA (10 mg/kg, i.p.) in mice in a manner similar to scavengers such as DMTU and trolox. Additionally, MH significantly scavenged intracellular ROS and Ca(2+) within hippocampal cells. The tight junction seals mediated by claudin (Cld-5) were also found to be modulated by MH. MH efficiently reduced 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50, 52.4 mM) and (•)OH with an electron spin resonance (ESR) signal rate constant of 4 × 10(9) M(-1) · S(-1), which is close to the reactivity of the vitamin E analog trolox. Taken together, these results suggest that MH may enhance radical scavenging in lipid and hydrophobic environments, which may be important for the physiological activity of the barrier.
    BioMed Research International 01/2015; 2015:893163. DOI:10.1155/2015/893163 · 2.71 Impact Factor
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    ABSTRACT: Mice lacking the IL-1R-associated kinase 4 (IRAK4) are completely resistant to LPS-induced endotoxic disorder or the TLR9 agonist CpG DNA plus d-galactosamine-induced acute liver injury (ALI), whereas wild-type strains succumb. However, translational drugs against sepsis or ALI remain elusive. Lonicerae flos extract is undergoing the clinical trial phase I in LPS-injected healthy human volunteers for sepsis treatment. In the current study, chlorogenic acid (CGA), a major anti-inflammatory constituent of lonicerae flos extract, rescued endotoxic mortality of LPS-intoxicated C57BL/6 mice, as well as ameliorated ALI of LPS/d-galactosamine-challenged C57BL/6 mice. As a mechanism, CGA inhibited various TLR agonist-, IL-1α-, or high-mobility group box-1-stimulated autophosphorylation (activation) of IRAK4 in peritoneal macrophages from C57BL/6 or C3H/HeJ mice via directly affecting the kinase activity of IRAK4, a proximal signal transducer in the MyD88-mediated innate immunity that enhances transcriptional activity of NF-κB or AP-1. CGA consequently attenuated protein or mRNA levels of NF-κB/AP-1 target genes encoding TNF-α, IL-1α, IL-6, and high-mobility group box-1 in vivo under endotoxemia or ALI. Finally, this study suggests IRAK4 as a molecular target of CGA in the treatment of innate immunity-related shock and organ dysfunction following insult of various TLR pathogens from bacteria and viruses. Copyright © 2014 by The American Association of Immunologists, Inc.
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    ABSTRACT: Belamcanda chinensis (L.) DC., which belongs to the family of Iridaceae, has been used as a folk medicine for the treatment of inflammation, asthma, tonsillitis, and many other throat disorders. Bioactivity-guided purification of the methylene chloride-soluble fraction of the rhizomes of B. chinensis based on the inhibition of nitric oxide production led to the identification of seventeen known compounds. Their structures were elucidated on the basis of extensive spectroscopic measurement such as NMR and ESI–MS. All of the isolated compounds were evaluated for their inhibitory effects on nitric oxide production in LPS-induced RAW 264.7 macrophage cells.
    Archives of Pharmacal Research 12/2014; DOI:10.1007/s12272-014-0529-8 · 1.75 Impact Factor
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    ABSTRACT: Bioactivity-guided fractionation of the MeOH extract from the roots of Sophora tonkinensis resulted in the isolation of a new pterocarpan glycoside (1) together with nine known compounds, maackiain (2), sophoranone (3), sophoranochromene (4), pinoresinol (5), syringaresinol (6), medioresinol (7), 4′,7-dihydroxyflavone (8), calycosin (9), and genistein (10). The structure of the new compound was determined on the basis of spectroscopic analysis including NMR and CD data in combination with acid hydrolysis. Compounds 1–4 exhibited the inhibitory effects on LPS-induced nitric oxide production with IC50 values ranging from 13.6 to 33.0 μM in RAW 264.7 macrophages.
    Bioorganic & Medicinal Chemistry Letters 12/2014; DOI:10.1016/j.bmcl.2014.12.012 · 2.33 Impact Factor
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    ABSTRACT: We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 μg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 μM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells.
    Archive für Toxikologie 11/2014; DOI:10.1007/s00204-014-1393-5 · 5.08 Impact Factor
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    ABSTRACT: The present study was conducted to investigate whether the high antioxidant activity induced by selenium (Sel) treatment and selenoprotein M (SelM) overexpression affected the protein profile of the brain cortex. To accomplish this, the changes in global protein expression were measured in transgenic (Tg) rats expressing human SelM (CMV/hSelM) and non‑Tg rats using two‑dimensional electrophoresis (2‑DE). The results revealed that: ⅰ) CMV/hSelM Tg rats showed a high level of enzyme activity for antioxidant protein in the brain cortex compared to non‑Tg rats; ⅱ) the high activity of these enzymes induced a decrease in total antioxidant concentration and γ‑secretase activity in CMV/hSelM Tg rats; ⅲ) five proteins were upregulated and three were downregulated by SelM overexpression; ⅳ) among the five upregulated proteins, two associated with creatine kinase B‑type (B‑CK) and E3 ubiquitin‑protein ligase RING1 (RING finger protein 1) were further increased in the two groups following Sel treatment, whereas synaptotagmin-15 (SytXV), eukaryotic translation initiation factor 4H (eIF-4H) and lactate dehydrogenase B (LDH-B) were increased or decreased under the same conditions; ⅴ) the three downregulated proteins did not induce a significant change in expression following Sel treatment; and ⅵ) the protein expression level alterations of the two selected spots (B‑CK and SytXV) identified by 2‑DE were extremely similar to the results from western blot analysis. Overall, the results of the present study provide primary novel biological evidence that new functional protein groups and individual proteins in the brain cortex of CMV/hSelM Tg rats are associated with Sel biology, including the response to Sel treatment and SelM overexpression.
    International Journal of Molecular Medicine 09/2014; 34(6). DOI:10.3892/ijmm.2014.1945 · 1.88 Impact Factor
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    ABSTRACT: Angiogenesis, which is initiated by certain tumor micro-environmental conditions and diverse protein factors, plays a pivotal role during tumor development and metastasis. Therefore, many efforts have been made to develop effective anti-angiogenic agents as anticancer therapeutics. In the current study, we investigated the anti-angiogenic potential of an ethanol extract of Annona atemoya seeds (EEAA) in vitro and in vivo.
    BMC Complementary and Alternative Medicine 09/2014; 14(1):353. DOI:10.1186/1472-6882-14-353 · 1.88 Impact Factor
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    ABSTRACT: Peroxiredoxin 6 (PRDX6) is a bifunctional protein with both glutathione peroxidase (GPx) and calcium-independent phospholipase A2 (iPLA2) activities. Expression of PRDX6 has been detected in human Parkinson's disease (PD) and dementia patients. However, no study has described PRDX6 function in the dopaminergic neurodegeneration in PD. Herein, we investigated the effects of PRDX6 on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration using PRDX6 transgenic (Tg) mice. Immunohistochemistry (IHC) and Western blot data for tyrosine hydroxylase (TH) showed that PRDX6 Tg mice had much higher loss of dopaminergic neurons by MPTP administration compared to non-Tg mice, as well as there was much higher behavioral impairment and astrocyte activation in PRDX6 Tg mice. MPTP-induced GPx activity was not different between PRDX6 Tg mice and non-Tg mice, which is accompanied by hyperoxidation of PRDX6. While iPLA2 activity was increased in PRDX6 Tg mice followed by an increase in the level of ROS and 4-hydroxynonenal (4-HNE). Intriguingly, the expression pattern of PRDX6 showed similar distribution and co-localization with astrocytes, but not neuron in the mouse and human brain. Furthermore, we demonstrated that iPLA2 activity of PRDX6 induced astrocytic activation followed by increased proinflammatory cytokines (TNF-α and IL1-β), 4-HNE, and PRDX6 hyperoxidation in primary cultured astrocytes. Our findings provide novel insights for PRDX6 function on nigrostriatal dopaminergic neuronal system, and we suggest that PRDX6 has an important role in dopaminergic neurodegeneration of PD.
    Molecular Neurobiology 09/2014; DOI:10.1007/s12035-014-8885-4 · 5.29 Impact Factor
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    ABSTRACT: Interleukin-32 (IL-32) is a cytokine produced by T lymphocytes, natural killer (NK) cells, monocytes and epithelial cells. There are five splicing variants (α, β, γ, δ, and ε) and IL-32γ is the most active isoform. We generated human IL-32γ transgenic (IL-32γ TG) mice, displaying a high level of IL-32γ expression in the pancreas. We investigated the effect of IL-32γ on streptozotocin (STZ)-induced type 1 diabetes model using IL-32γ TG mice. After a suboptimal diabetogenic dose of STZ administration, IL-32γ TG mice showed significantly increased blood glucose level comparing with that of wild type (WT) mice at day 5. Inflammatory cytokines levels such as, IL-6, TNFα, IFNγ and IL-1β, in pancreas and liver lysates were accessed by a specific cytokine ELISA. The proinflammatory cytokines were significantly enhanced in the pancreas of IL-32γ TG mice comparing to that of WT mice whereas those cytokines levels in liver of IL-32γ TG and WT mice were not changed by STZ. These data indicate that the overexpression of IL-32γ contributes to initial islet β-cells injury and inflammation in pancreas and aggravates STZ-induced type 1 diabetes.
    Cytokine 09/2014; 69(1):1–5. DOI:10.1016/j.cyto.2014.05.002 · 2.87 Impact Factor

Publication Stats

4k Citations
856.68 Total Impact Points

Institutions

  • 2002–2015
    • Chungbuk National University
      • College of Pharmacy
      Chinsen, Chungcheongbuk-do, South Korea
  • 2013
    • Ewha Womans University
      • College of Pharmacy
      Sŏul, Seoul, South Korea
    • Nanchang University
      Nan-ch’ang-shih, Jiangxi Sheng, China
    • Pusan National University
      • Department of Biomaterials Science
      Pusan, Busan, South Korea
  • 2012
    • Yeungnam University
      • College of Pharmacy
      Asan, South Chungcheong, South Korea
  • 2006–2012
    • Konkuk University
      • • Department of Bioscience and Technology
      • • Bio/Molecular Informatics Center
      Sŏul, Seoul, South Korea
  • 2011
    • Chonbuk National University
      • College of Veterinary Medicine
      Seoul, Seoul, South Korea
  • 1998–2011
    • Korea Food and Drug Administration
      Seishō-gun, North Gyeongsang, South Korea
  • 2003–2009
    • Korea Research Institute of Bioscience and Biotechnology KRIBB
      • • Bioevaluation Center
      • • Laboratory of Cellular Biology
      Ansan, Gyeonggi, South Korea
  • 2008
    • Safety Research Institute
      Georgia, United States