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Arsenic Trioxide Induces Apoptosis in Chronic Myelogenous Leukemia K562 Cells:Possible Involvement of p38 MAP Kinase

  • Shim, Moon-Jeong;Kim, Hyun-Jeong;Yang, Seung-Ju;Lee, In-Soo;Choi, Hyun-Il;Kim, Tae-Ue
    • BMB Reports
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    • v.35 no.4
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    • pp.377-383
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    • 2002
  • Arsenic trioxide ($As_O_3$) was recently demonstrated to be an effective inducer of apoptosis in patients with relapsed acute promyelocytic leukemia (APL) as well as patients with APL in whom all-trans-retinoic acid and conventional chemotherapy failed. Chronic myelogenous leukemia cells are highly resistant to chemotherapeutic drugs. To determine if $As_O_3$ might be useful for the treatment of chronic myelogenous leukemia, we examined the ability of $As_O_3$ to induce apoptosis in K562 cells. In vitro cytotoxicity of $As_O_3$ was evaluated in K562 cells by a MTT assay: the $IC_50$ value for $As_O_3$ was determined to be $10\;{\mu}m$. When analyzed by agarose gel electorphoresis, the DNA fragments became evident after incubation of the cells with $20\;{\mu}m$ $As_O_3$ for 24 h. We also found morphological changes and chromatin condensation of the cells undergoing apoptosis. Activation of caspase-3 was observed 6 h after treatment with $20\;{\mu}m$ $As_O_3$ by a Western blot analysis. Next, we examined the MAP kinase-signaling pathway of $As_O_3$-induced apoptosis in K562 cells. $As_O_3$ at $10\;{\mu}m$ strongly induced the activation of p38, inhibited $As_O_3$ induced apoptotic cell death. These results suggest that $As_O_3$ is able to induce the apoptotic activity in K562 cells, and its apoptotic mechanism may be associated with the activation of p38.

Effect of Particle Size on the Dielectric and Piezoelectric Properties of 0.95(K0.5Na0.5)NbO3-0.05BaTiO3 Lead-free Piezoelectric Ceramics

  • Bae, Seon-Gi;Shin, Hyea-Gyiung;Chung, Kwang-Hyun;Yoo, Ju-Hyun;Im, In-Ho
    • Transactions on Electrical and Electronic Materials
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    • v.16 no.4
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    • pp.179-182
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    • 2015
  • The particle sizes of 0.95(K0.5Na0.5)NbO3-0.05BaTiO3 powder were controlled by secondary milling time after calcination. The average particle sizes, Dmean, of 0.95(K0.5Na0.5)NbO3-0.05BaTiO3 powders were critically changed from 14.31 μm to 0.91 μm by secondary milling time. The dielectric and piezoelectric properties of 0.95(K0.5Na0.5)NbO3-0.05BaTiO3 ceramics depended on the particle sizes of powders after calcination and the secondary milling process. As secondary milling times after calcination were increased to more than 48 hr, the dielectric and piezoelectric properties of 0.95(K0.5Na0.5)NbO3-0.05BaTiO3 ceramics were deteriorated.

Korean Red Ginseng inhibits apoptosis in neuroblastoma cells via estrogen receptor ${\beta}$-mediated phosphatidylinositol-3 kinase/Akt signaling

  • Nguyen, Cuong Thach;Luong, Truc Thanh;Kim, Gyu-Lee;Pyo, Suhkneung;Rhee, Dong-Kwon
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.69-75
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    • 2015
  • Background: Ginseng has been shown to exert antistress effects both in vitro and in vivo. However, the effects of ginseng on stress in brain cells are not well understood. This study investigated how Korean Red Ginseng (KRG) controls hydrogen peroxide-induced apoptosis via regulation of phosphatidylinositol-3 kinase (PI3K)/Akt and estrogen receptor (ER)-${\beta}$ signaling. Methods: Human neuroblastoma SK-N-SH cells were pretreated with KRG and subsequently exposed to $H_2O_2$. The ability of KRG to inhibit oxidative stress-induced apoptosis was assessed in MTT cytotoxicity assays. Apoptotic protein expression was examined byWestern blot analysis. The roles of ER-${\beta}$, PI3K, and p-Akt signaling in KRG regulation of apoptosis were studied using small interfering RNAs and/or target antagonists. Results: Pretreating SK-N-SH cells with KRG decreased expression of the proapoptotic proteins p-p53 and caspase-3, but increased expression of the antiapoptotic protein BCL2. KRG pretreatment was also associated with increased ER-${\beta}$, PI3K, and p-Akt expression. Conversely, ER-${\beta}$ inhibition with small interfering RNA or inhibitor treatment increased p-p53 and caspase-3 levels, but decreased BCL2, PI3K, and p-Akt expression. Moreover, inhibition of PI3K/Akt signaling diminished p-p53 and caspase-3 levels, but increased BCL2 expression. Conclusion: Collectively, the data indicate that KRG represses oxidative stress-induced apoptosis by enhancing PI3K/Akt signaling via upregulation of ER-${\beta}$ expression.

Allelic Variation of Glutenin, Granule-Bound Starch Synthase l and Puroindoline in Korean Wheat Cultivar

  • Park, Chul-Soo;Pena, Roberto J.;Baik, Byung-Kee;Kang, Chon-Sik;Heo, Hwa-Young;Cheong, Young-Keun;Woo, Sun-Hee
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.54 no.2
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    • pp.181-191
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    • 2009
  • To investigate the genetic variation of high-and low-molecular-weight glutenin subunits (BMW-GS and LMW-GS), granule-bound starch synthase I (GBSSI) and puroindoline in 24 Korean wheat cultivars. At the BMW-GS compositions, three Glu-A1 alleles, five Glu-B1 alleles and three Glu-D1 alleles were identified. The high frequency of alleles at each locus was Glu-A1c allele (15 cultivars), Glu-B1b allele (16 cultivars) and Glu-D1f allele (16 cultivars). Four alleles were identified at the Glu-A3 and Glu-B3 loci and three at Glu-D3 locus and Glu-A3d, Glu-B3d and Glu-D3a were mainly found at each Glu-3 locus. Glu-A3d, Glu-B3d, Glu-D3b or c (4 cultivars, respectively) and Glu-A3d, Glu-B3d, Glu-D3a and Glu-A3c, Glu-B3d or h, Glu-D3a (3 cultivar, respectively) were predominantly found in Korean wheats. At the GBSS compositions, 2 waxy wheat cultivars, Shinmichal and Shinmichal1, showed null alleles on the Wx loci and other cultivars were wild type in GBSS compositions. At the puroindoline gene compositions, Korean wheat cultivars carried 3 genotypes, which 10 cultivars (41.7%) were Pina-D1a and Pinb-D1a, 11 cultivars (45.8%) had Pina-D1a and Pinb-D1b and 3 cultivars (12.5%) carried Pina-D1b and Pinb-D1a. These genetic variations could present the information to improve flour and end-use quality in Korean wheat breeding programs.

Expression and Prognostic Role of MEKK3 and pERK in Patients with Renal Clear Cell Carcinoma

  • Chen, Qi;Lu, Hong-sheng;Gan, Mei-fu;Chen, Lan-xi;He, Kai;Fan, Guang-min;Cao, Xue-quan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2495-2499
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    • 2015
  • Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) is an important serine/threonine protein kinase and a member of the MAPK family. MEKK3 can effectively activate the MEK/ERK signaling pathway and promote an autocrine growth loop critical for tumor genesis, cell proliferation, terminal differentiation, apoptosis and survival. To explore the relationship between MEKK3 and cell apoptosis, clinicopathology and prognosis, we characterize the expression of MEKK3, pERK and FoxP3 in the renal clear cell carcinoma (RCCC). Protein expression was detected by tissue microarray and immunochemistry in 46 cases of RCCC and 28 control cases. Expression levels of CD3+,CD3+CD4+,CD3+CD8+,CD4+CD25+, CD4+CD25+ FoxP3+ were assessed by flow cytometry and analyzed for their association with pathological factors, correlation and prognosis in RCCC. Expression of MEKK3, pERK and FoxP3 was significantly up-regulated in RCCC as compared to control levels (p<0.01), associated with pathological grade (p<0.05)and clinical stage (p<0.05). CD4+CD25+ Foxp3+ Treg cells were also significantly increased in RCCC patients (p<0.05). Cox multivariate regression analysis showed that MEKK3, pERK expression and patholigical stage were independent prognostic factors in patients with RCCC (p<0.05). MEKK3 can be used as an important marker of early diagnosis and prognostic evaluation in RCCC. It may be associated with imbalance of anti-tumor immunity and overexpression of pERK. Expression of MEKK3 and pERK are significantly increased in RCCC, with protein expression and clinical stage acting as independent prognostic factors.

Epigenetic and Glucocorticoid Receptor-Mediated Regulation of Glutathione Peroxidase 3 in Lung Cancer Cells

  • An, Byung Chull;Jung, Nak-Kyun;Park, Chun Young;Oh, In-Jae;Choi, Yoo-Duk;Park, Jae-Il;Lee, Seung-won
    • Molecules and Cells
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    • v.39 no.8
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    • pp.631-638
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    • 2016
  • Glutathione peroxidase 3 (GPx3), an antioxidant enzyme, acts as a modulator of redox signaling, has immunomodulatory function, and catalyzes the detoxification of reactive oxygen species (ROS). GPx3 has been identified as a tumor suppressor in many cancers. Although hyper-methylation of the GPx3 promoter has been shown to down-regulate its expression, other mechanisms by which GPx3 expression is regulated have not been reported. The aim of this study was to further elucidate the mechanisms of GPx3 regulation. GPx3 gene analysis predicted the presence of ten glucocorticoid response elements (GREs) on the GPx3 gene. This result prompted us to investigate whether GPx3 expression is regulated by the glucocorticoid receptor (GR), which is implicated in tumor response to chemotherapy. The corticosteroid dexamethasone (Dex) was used to examine the possible relationship between GR and GPx3 expression. Dex significantly induced GPx3 expression in H1299, H1650, and H1975 cell lines, which exhibit low levels of GPx3 expression under normal conditions. The results of EMSA and ChIP-PCR suggest that GR binds directly to GRE 6 and 7, both of which are located near the GPx3 promoter. Assessment of GPx3 transcription efficiency using a luciferase reporter system showed that blocking formation of the GR-GRE complexes reduced luciferase activity by 7-8-fold. Suppression of GR expression by siRNA transfection also induced down-regulation of GPx3. These data indicate that GPx3 expression can be regulated independently via epigenetic or GR-mediated mechanisms in lung cancer cells, and suggest that GPx3 could potentiate glucocorticoid (GC)-mediated anti-infla-mmatory signaling in lung cancer cells.

Electrical Properties of $(x)BaTiO_3-(1-x)SrTiO_3$ Ceramic with Variation of $SrTiO_3$ Substitution ($SrTiO_3$ 고용에 따른 $(x)BaTiO_3-(1-x)SrTiO_3$ 세라믹의 전기적 특성)

  • Jang, Dong-Hwan;Ki, Hyun-Chul;Hong, Hyung-Jin;Jung, Woo-Sung;Kim, Tae-Sung
    • Proceedings of the KIEE Conference
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    • 1998.11c
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    • pp.795-797
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    • 1998
  • A $BaTiO_3$, ferroelectric material, was mixed $SrTiO_3$, $(x)BaTiO_3-(1-x)SrTiO_3$($0.7{\leq}x{\leq}1$) ceramic capacitor with stable electrical properties in high voltage was fabricated. And microstructure, electrical property were investigated with $SrTiO_3$ mol ratio. The shrinkage, open porosity, sintering density were predominated at $9BaTiO_3-0.1SrTiO_3$. Increasing $SrTiO_3$ mol ratio, curie temperature was shifted at low temperature and maximum permittivity was increased. Also, $0.9BaTiO_3-0.1SrTiO_3$ was showed stable dielectric properties at $25{\sim}80[^{\circ}C]$. V-I properties of specimen were observed in the temperature range of $21{\sim}143[^{\circ}C]$, were divided into three regions. The region I below 10[kV/cm] was shown Ohmic conduction, the region II from 10 to 30[kV/cm] was explained by the Poole-Frenkel emission theory and the region III above 30[kV/cm] was analysed by the tunneling effect.

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Thermoelectric Properties of the n-type $Bi_2(Te,Se)_3$ Processed by Hot Pressing (n형 $Bi_2(Te,Se)_3$ 가압소결체의 열전특성)

  • Park, D.H.;Roh, M.R.;Kim, M.Y.;Oh, T.S.
    • Journal of the Microelectronics and Packaging Society
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    • v.17 no.2
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    • pp.49-54
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    • 2010
  • The n-type $Bi_2(Te,Se)_3$ powders were fabricated by melting/grinding method and were hot-pressed in order to compare thermoelectric properties of the hot-pressed specimens with those of the $Bi_2(Te,Se)_3$ ingot. Effects of mechanical milling treatment of the $Bi_2(Te,Se)_3$ powders on thermoelectric characteristics of a hot-pressed specimen were also examined. The hot-pressed $Bi_2(Te,Se)_3$ exhibited power factors of $27.3{\sim}32.3{\times}10^{-4}W/m-K^2$ which were superior to $24.2{\times}10^{-4}W/m-K^2$ of the ingot. The $Bi_2(Te,Se)_3$, hot-pressed after mechanical milling treatment of the powders, possessed a non-dimensional figure-of-merit of 1.02 at $100^{\circ}C$ and exhibited extrinsic-intrinsic transition at $130^{\circ}C$.

Inhibition of Adipogenesis in 3T3-L1 Adipocytes with Ethanol Extracts of Saururus chinensis (삼백초 추출물의 3T3-L1 세포에 대한 지방축적 억제효과)

  • Shin, Ok-Su;Shin, Youn-Ho;Lee, Kang-Hyun;Kim, Gun-Yong;Kim, Ki-Ho;Park, Jung-Keug;Ahn, Jae-Il;Song, Kye-Yong
    • KSBB Journal
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    • v.27 no.6
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    • pp.381-386
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    • 2012
  • Obesity increases the risk of many adult diseases, such as atherosclerosis, diabetes, hypertension, ischemic heart disease and breast cancer. Inhibition of adipogenesis is an effective way in the anti-obesity management. Because of main components of Saururus chinensis is flavonoid, it has been showed some improvement by its antioxidant effects on the atherosclerosis, heart disease and diabetic hyperlipidemia. But mechanism of anti-obesity effect of S. chinensis is not clear. We investigated the effects of ethanol extracts of S. chinensis on adipogenesis in the 3T3-L1 pre-adipocyte. The 3T3-L1 cell line is commonly used to study adipogenesis in vitro. In this study, ethanol extracts of S. chinensis significantly decrease the lipid accumulation in the 3T3-L1 cells proved by measuring triglyceride contents and Oil red O staining. The proposed mechanism of inhibition of adipogenesis in the 3T3-L1 cells with ethanol extracts of S. chinensis is down-regulation of transcriptional factors and adipocyte-specific genes such CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$) and Peroxisome proliferator activated receptor ${\gamma}$ ($PPAR{\gamma}$) in concentration dependent pattern. These results suggest that ethanol extracts of S. chinensis inhibits adipognesis in the 3T3-L1 cells and can be used as a safe and efficient natural substance to manage anti-obesity.

Synthesis of Nano Size $BaCeO_3$ as an Effective Flux Pining Center for YBCO Superconductor (YBCO 초전도체의 효과적인 플럭스 피닝 센터로서의 나노 크기 $BaCeO_3$ 합성)

  • Youn, J.S.;No, K.S.;Kim, Y.H.;Jun, B.H.;Lee, J.P.;Jung, S.Y.;Kim, C.J.
    • Progress in Superconductivity
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    • v.10 no.1
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    • pp.12-16
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    • 2008
  • In this work, nano size $BaCeO_3$, which is a possible flux pinning medium of melt processed $YBa_{2}Cu_{3}O_x$ superconductor, was synthesized by the conventional solid state reaction method using powders. $BaCeO_3$ and $CeO_2$ were mixed thoroughly using a ball milling for 24 hours and calcined at $1200^{\circ}C$ for 5 hours for the formation $BaCeO_3$ powder. The obtained $BaCeO_3$ powder was attrition milled at various milling times of 60 min, 120 min and 240 min. The $BaCeO_3$ powders of various milling times were mixed with $YBa_{2}Cu_{3}O_x$ powder. Seed melt processed $YBa_{2}Cu_{3}O_x$-$BaCeO_3$ (15wt.%) superconductors were prepared and the superconducting properties were investigated. It was found that $T_c$ of $Y_{1.5}Ba_{2}Cu_{3}O_x$ samples was not significantly affected by $BaCeO_3$ addition, but $J_c$ of samples was increased by $BaCeO_3$ addition. The $J_c$ improvement by fine $BaCeO_3$ powder (120 min attrition-milled) was effective at low magnetic fields less than 2 T.

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