Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway

Park, Y-H,Kim, S-U,Kwon, T-H,Kim, J-M,Song, I-S,Shin, H-J,Lee, B-K,Bang, D-H,Lee, S-J,Lee, D-S,Chang, K-T,Kim, B-Y,Yu, D-Y Macmillan Publishers Limited 2016 Oncogene Vol.35 No.27

<P>The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently- expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.</P>

Integrin αvβ3-mediated transcriptional regulation of TIMP-1 in a human ovarian cancer cell line

Kim, D.S.,Jeon, O.H.,Lee, H.D.,Yoo, K.H.,Kim, D.S. Academic Press 2008 Biochemical and biophysical research communication Vol.377 No.2

We have previously reported that a disintegrin inhibits solid tumor growth and metastasis in mouse model [I.C. Kang, Y.D. Lee, D.S. Kim, A novel disintegrin salmosin inhibits tumor angiogenesis, Cancer Res. 59 (1999) 3754-3760; S.I. Kim, K.S. Kim, H.S. Kim, D.S. Kim, Y. Jang, K.H. Chung, Y.S. Park, Inhibitory effect of the salmosin gene transferred by cationic liposomes on the progression of B16BL6 tumors, Cancer Res. 63 (2003) 6458-462]. In this study, we have investigated the modulatory effect of a disintegrin, saxatilin, on the balance between MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in human ovarian cancer cell line MDAH 2774. Functional mechanism of the disintegrin-mediated transcriptional regulation of MMP-9 and TIMP-1 was examined in the ovarian cancer cell line. Saxatilin strongly induced TIMP-1 expression in dose- and time-dependent manners, while the disintegrin suppressed MMP-9 expression. Further analyses clearly indicated that interaction of the disintegrin and integrin αvβ3 results in the TIMP-1 promoter activation via c-fos to suppress TNF-α-induced cancer cell invasion. These results demonstrate that integrin αvβ3-mediated transcriptional regulation of MMP-9 and TIMP-1 is critical for suppressing the ovarian cancer cell invasion.

Genetic and phylogenetic characterizations of a novel genotype of highly pathogenic avian influenza (HPAI) H5N8 viruses in 2016/2017 in South Korea

Kim, Y.I.,Park, S.J.,Kwon, H.I.,Kim, E.H.,Si, Y.J.,Jeong, J.H.,Lee, I.W.,Nguyen, H.D.,Kwon, J.J.,Choi, W.S.,Song, M.S.,Kim, C.J.,Choi, Y.K. Elsevier Science 2017 INFECTION GENETICS AND EVOLUTION Vol.53 No.-

<P>During the outbreaks of highly pathogenic avian influenza (HPAI) H5N6 viruses in 2016 in South Korea, novel H5N8 viruses were also isolated from migratory birds. Phylogenetic analysis revealed that the HA gene of these H5N8 viruses belonged to clade 2.3.4.4, similarly to recent H5Nx viruses, and originated from A/Brk/Korea/Gochang1/14(H5N8), a minor lineage of H5N8 that appeared in 2014 and then disappeared. At least four reassortment events occurred with different subtypes (H5N8, H7N7, H3N8 and H10N7) and a chicken challenge study revealed that they were classified as HPAI viruses according to OIE criteria. (C) 2017 Elsevier B.V. All rights reserved.</P>

Enhanced H₂ fermentation of organic waste by CO₂ sparging

Kim, D.H.,Shin, H.S.,Kim, S.H. Pergamon Press ; Elsevier Science Ltd 2012 International journal of hydrogen energy Vol.37 No.20

This study aimed to improve the productivity of dark fermentative hydrogen production from organic waste. An anaerobic sequencing batch reactor was used for hydrogen fermentation and it was fed with food waste (VS 4.4 +/- 0.2% containing 27 g carbohydrate-COD/L) at various CO<SUB>2</SUB> sparging rates (40-120 L/L/d), hydraulic retention times (HRTs; 18-42 h), and solid retention times (SRTs; 18-160 h). CO<SUB>2</SUB> sparging increased the H<SUB>2</SUB> productivity by 5-36% at all the examined conditions, confirming the benefit of the replacement of headspace gas by CO<SUB>2</SUB>. The maximum H<SUB>2</SUB> production was obtained by CO<SUB>2</SUB> sparging at 80 L/L/d, resulting in the H<SUB>2</SUB> productivity of 3.18 L H<SUB>2</SUB>/L/d and the H<SUB>2</SUB> yield of 97.3 mL H<SUB>2</SUB>/g VS<SUB>added</SUB>. Increase of n-butyrate and isopropanol yields were concurrent with the enhanced H<SUB>2</SUB> yield by CO<SUB>2</SUB> sparging. Acidogenic efficiency, the sum of H<SUB>2</SUB>, organic acid, and alcohol, in the CO<SUB>2</SUB>-sparged reactor ranged from 47.9 to 56.0%, which was comparable to conventional acidogenesis. Thermodynamic analysis confirmed that both CO<SUB>2</SUB> sparging and CO<SUB>2</SUB> removal were beneficial for H<SUB>2</SUB>-producing reactions, but CO<SUB>2</SUB> sparing has more profound effect than CO<SUB>2</SUB> removal on inhibiting H<SUB>2</SUB>-consuming reactions.

Effect of substrate concentration on continuous Photo-fermentative hydrogen production from lactate using Rhodobacter sphaeroides

Kim, D.H.,Son, H.,Kim, M.S. Pergamon Press ; Elsevier Science Ltd 2012 INTERNATIONAL JOURNAL OF HYDROGEN ENERGY - Vol.37 No.20

The information on continuous operation and the use of actual waste as a feedstock are essential for the practical application of photo-fermentative H<SUB>2</SUB> production. For the first 200 days, continuous H<SUB>2</SUB> production from lactate was attempted using purple non-sulfur (PNS) bacteria, Rhodobacter sphaeroides KD131, under an illumination of 110 W/m<SUP>2</SUP>. During the continuous operation, 30% of the fermenter volume was replaced by fresh feedstock once a day, and substrate concentration was gradually increased from 5 mM to 30 mM. H<SUB>2</SUB> production was negligible at 5 mM, which was ascribed to the fact that the electrons contained in lactate were mostly consumed for cell growth and soluble microbial products (SMPs) production. As lactate concentration increased, H<SUB>2</SUB> production gradually increased and reached a maximum at 20 mM, showing a substrate conversion efficiency (SCE) of 38%, a H<SUB>2</SUB> yield of 2.3 mol H<SUB>2</SUB>/mol lactate<SUB>added</SUB>, and a H<SUB>2</SUB> production rate of 309 mL H<SUB>2</SUB>/L-fermenter/d. Further increases of lactate concentration resulted in a drop of H<SUB>2</SUB> production (<1.0 mol H<SUB>2</SUB>/mol lactate<SUB>added</SUB>). When the feedstock was changed to actual waste obtained from a 1-day lactate fermentation of food waste, stable H<SUB>2</SUB> production was maintained, but showed a decreased SCE of 24%. It was speculated that the low performance was due to the fact that actual waste contained not only pure lactate but also other organic compounds that could not be utilized by PNS bacteria. In addition, compared to feeding with pure lactate, the electron consumption to the cell growth was higher in feeding with actual waste, which led to the lower performance.

Exendin-4 induction of cyclin D1 expression in INS-1 beta-cells: involvement of cAMP-responsive element.

Kim, M-J,Kang, J-H,Park, Y G,Ryu, G R,Ko, S H,Jeong, I-K,Koh, K-H,Rhie, D-J,Yoon, S H,Hahn, S J,Kim, M-S,Jo, Y-H Journal of Endocrinology, Ltd. [etc.] 2006 The Journal of endocrinology Vol.188 No.3

<P>Glucagon-like peptide-1 (GLP-1) and its analog exendin-4 (EX) have been considered as a growth factor implicated in pancreatic islet mass increase and beta-cell proliferation. This study aimed to investigate the effect of EX on cyclin D1 expression, a key regulator of the cell cycle, in the pancreatic beta-cell line INS-1. We demonstrated that EX significantly increased cyclin D1 mRNA and subsequently its protein levels. Although EX induced phosphorylation of Raf-1 and extracellular-signal-regulated kinase (ERK), both PD98059 and exogenous ERK1 had no effect on the cyclin D1 induction by EX. Instead, the cAMP-elevating agent forskolin induced cyclin D1 expression remarkably and this response was inhibited by pretreatment with H-89, a protein kinase A (PKA) inhibitor. Promoter analyses revealed that the cAMP-responsive element (CRE) site (at position -48; 5'-TAACGTCA-3') of cyclin D1 gene was required for both basal and EX-induced activation of the cyclin D1 promoter, which was confirmed by site-directed mutagenesis study. For EX to activate the cyclin D1 promoter effectively, CRE-binding protein (CREB) should be phosphorylated and bound to the putative CRE site, according to the results of electrophoretic mobility shift and chromatin immunoprecipitation assays. Lastly, a transfection assay employing constitutively active or dominant-negative CREB expression plasmids clearly demonstrated that CREB was largely involved in both basal and EX-induced cyclin D1 promoter activities. Taken together, EX-induced cyclin D1 expression is largely dependent on the cAMP/PKA signaling pathway, and EX increases the level of phosphorylated CREB and more potently trans-activates cyclin D1 gene through binding of the CREB to the putative CRE site, implicating a potential mechanism underlying beta-cell proliferation by EX.</P>

Effect of the Length of Feed Withdrawal on Weight Loss, Yield and Meat Color of Broiler

Kim, D.H.,Yoo, Y.M.,Kim, S.H.,Jang, B.G.,Park, B.Y.,Cho, S.H.,Seong, P.N.,Hah, K.H.,Lee, J.M.,Kim, Y.K.,Hwang, I.H. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.1

The current study was conducted to determine the optimum length of feed withdrawal for pre-harvest broilers. A total of three hundred broilers were sampled from an industrial population, and 30 chicks for each weight group (e.g., 1.5 and 2.5 kg) were randomly assigned to feed withdrawal treatments for 0, 3, 6, 9 and 12 h. Weight loss, yield, muscle pH, objective meat color and weights of gastro intestinal contents, crop, gizzard, provenriculus, small intestine, caecum, and rectum were determined. Live weight loss was significantly (p<0.05) increased as length of feed withdrawal extended. A significant (p<0.05) carcass yield for both 1.5 and 2.5 kg groups coincided after 9 and 6 h feed withdrawal, respectively. Net weights of intestinal contents for crop and gizzard were significantly (p<0.05) reduced by 6 h, and the reduction for proventriculus and small intestine occurred from 3 h. A noticeable effect of feed withdrawal on pH for breast muscle at 3 h postmortem occurred only when chicks were fasted for 3 h of which pH (6.05) was significantly (p<0.05) higher than that for other groups including the control (5.74). There was a linear tendency of higher lightness (Hunter L* value) numerically for chicks fasted for longer periods. The highest coefficient of determinations of regression models to estimate weight loss as a function of fasting period and body weights were achieved, when the models included both linear and quadratic terms for fasting period, and linear term for both 1.5 ($R^2=0.76$) and 2.5 kg ($R^2=0.78$) body weight groups. Given the practical aspect, approximately 1.5 kg of body weight is dominant, weight loss could be predicted by the following function; live weight $loss=26.6-0.28{\times}(fasting period)^2+12.34{\times}pasting\;period-0.012{\times}body\;weight$, $R^2=0.76$. Current data implied that the optimum fasting time for pre-slaughter chicks varied depending on slaughter weight; 6 and 9-h fasting were recommendable for 2.5 and 1.5 kg chicks, with little effect on objective meat color.

15-Deoxy-Δ^12,14-prostaglandin J₂ induces p53 expression through Nrf2-mediated upregulation of heme oxygenase-1 in human breast cancer cells

Kim, D. H.,Song, N. Y.,Kim, E. H.,Na, H. K.,Joe, Y.,Chung, H. T.,Surh, Y. J. Informa Healthcare 2014 Free radical research Vol.48 No.9

<P>Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that has antioxidant and cytoprotective functions. However, HO-1 has oncogenic functions in cancerous or transformed cells. In the present work, we investigated the effects of HO-1 on the expression of p53 induced by 15-deoxy-Δ<SUP>12,14</SUP>-prostaglandin J<SUB>2</SUB> (15d-PGJ<SUB>2</SUB>) in human breast cancer (MCF-7) cells. Treatment of MCF-7 cells with 15d-PGJ<SUB>2</SUB> led to time-dependent increases in the expression of p53 as well as HO-1. Upregulation of p53 expression by 15d-PGJ<SUB>2</SUB> was abrogated by si-RNA knock-down of HO-1. In MCF-7 cells transfected with HO-1 si-RNA, 15d-PGJ<SUB>2</SUB> failed to induce expression of p53 as well as HO-1. In addition, HO-1 inducers enhanced the p53 expression. We speculated that iron, a by-product of HO-1-catalyzed reactions, could mediate 15d-PGJ<SUB>2</SUB>-induced p53 expression. Upregulation of p53 expression by 15d-PGJ<SUB>2</SUB> was abrogated by the iron chelator desferrioxamine in MCF-7 cells. Iron released from heme by HO-1 activity is mostly in the Fe<SUP>2+</SUP> form. When MCF-7 cells were treated with the Fe<SUP>2+</SUP>-specific chelator phenanthroline, 15d-PGJ<SUB>2</SUB>-induced p53 expression was attenuated. In addition, levels of the Fe-sequestering protein H-ferritin were elevated in 15d-PGJ<SUB>2</SUB>-treated MCF-7 cells. In conclusion, upregulation of p53 and p21 via HO-1 induction and subsequent release of iron with accumulation of H-ferritin may confer resistance to oxidative damage in cancer cells frequently challenged by redox-cycling anticancer drugs.</P>

Cyclobuxine D의 토끼 적출 장관에 대한 작용

이종화,박영현,조병헌,김종배,김정목,김유재,김천숙,차영덕,김영석 최신의학사 1988 最新醫學 Vol.31 No.1

비타민 D3 의 경구투여 또는 자외선 조사가 브로일러 병아리의 증체 및 비타민 D3 대사에 미치는 영향

장윤환(Y . H . Chiang),황선일(S . I . Hwang),김중달(J . D . Kim),M . F . Holick(M . F . Holick) 한국영양사료학회 1995 韓國營養飼料學會誌 Vol.19 No.6