Decitabine, a DNA methyltransferases inhibitor, induces cell cycle arrest at G2/M phase through p53-independent pathway in human cancer cells

Shin, D.Y.,Sung Kang, H.,Kim, G.Y.,Kim, W.J.,Yoo, Y.H.,Choi, Y.H. Masson Pub. USA, Inc 2013 Biomedicine & pharmacotherapy Vol.67 No.4

Decitabine (5-aza-2'-deoxycytidine), an inhibitor of DNA methyltransferases, has a wide range of anti-metabolic and anti-cancer activities. Decitabine also induces cell cycle arrest at G2/M phase and apoptosis in human cancer cells. However, the cellular and molecular mechanisms of this cell cycle arrest are poorly understood. In the present study, we investigated the roles of the tumor suppressor p53 and the cyclin-dependent kinase (Cdk) inhibitor p21 following decitabine-induced G2/M arrest in human cancer cells. DNA flow cytometric analyses indicated that decitabine induced a G2/M arrest in AGS gastric and A549 lung carcinoma cell lines, which have wild type p53. Western blot analyses using whole cell lysates from AGS cells demonstrated that decitabine treatment did not change the steady-state level of Cdks and Cdk inhibitor p27, but it partially inhibited expression of cyclin A, cyclin B1, and Cdc25C proteins. However, similar results were found using the A549 cell line, where decitabine induced a dramatic up-regulation of both p53 and p21 expression, and the increased levels of p21 were associated with increased binding of p21 with Cdks, cyclin A, and cyclin B1. Knockdown of p53 by small interfering RNA (siRNA) markedly abolished p53 induction by decitabine in AGS cells, yet p53 siRNA had no attenuating effect on p21 induction. In addition, depletion of p21 expression with siRNA, but not p53, significantly attenuated decitabine-induced G2/M arrest. We also observed that decitabine strongly induced G2/M arrest associated with p21 induction in both p53 allele-null (-/-) HCT116 and wild type p53 (+/+) HCT116 cell lines. Therefore, our data indicated that p21 plays a crucial role in decitabine-induced G2/M arrest and operates in a p53-independent manner.

액상사료 자동급이기를 이용한 포유자돈의 조기이유가 자돈 생산성에 미치는 영향

유용희,박홍석,정일병,박준철,한정대,이덕수,장병귀 한국동물자원과학회 2001 한국축산학회지 Vol.43 No.4

In order to investigate the performance of an automatic liquid feeder for suckling piglets that was developed recently by NLRI(National Livestock Research Institute) in Korea and the effect of its use for weaning piglets at very early age(14days of age), a feeding trial was conducted with 60 suckling piglets. The control piglets were raised by their own sows until 21d, while others were shifted to liquid feeding at 14d, for one week, then all the piglets were fed the same mash diet until 70days of age. An automatic liquid feeder imported from USA that was used by swine farmers was used for a comparative propose. The growth rate and feed utilization, diarrhea of piglets, and the development of digestive tracts were studied. Results obtained are as follows. The 21st day body weights of piglets weaned at 14d, and fed liquid diet were significantly lower(P$lt;.05) than those of the control piglets weaned at 21d,(7.10 vs 5.85 & 5.99 ㎏/head), but they grew fast and their weights exceeded those of the control piglets at 70days of age (26.42 vs. 28.88 & 27.76 ㎏/head). Consequently, their weight gain during the period of feeding mash diet were significantly higher(P$lt;.05) than those of the control piglets(19.31 vs 23.38 & 22.37 ㎏/head). There were no remarkable differences, in feed conversion ratio(1.98 vs 2.00 & 2.03). Liquid feeding showed no difference in the incidence of piglet diarrhea from each automatic liquid feeder. However, liquid feeding showed much low jejunal villi height at the 3rd day of feeding mash diet, though they were recovered at the 7th day. There was no difference in all the performance between the automatic liquid feeder developed by NLRI in Korea and the Commercial. Based on results of this study, it can be concluded that the automatic liquid feeder developed at NLRI in Korea performed successfully and can be used for weaning of piglets at very early age (14days old). It also can be said that weaning piglets at very early age would be stimulated piglet growth afterwards.

The E3 ubiquitin ligase CHIP selectively regulates mutant epidermal growth factor receptor by ubiquitination and degradation

Chung, C.,Yoo, G.,Kim, T.,Lee, D.,Lee, C.S.,Cha, H.R.,Park, Y.H.,Moon, J.Y.,Jung, S.S.,Kim, J.O.,Lee, J.C.,Kim, S.Y.,Park, H.S.,Park, M.,Park, D.I.,Lim, D.S.,Jang, K.W.,Lee, J.E. Academic Press 2016 Biochemical and biophysical research communication Vol.479 No.2

Somatic mutation in the tyrosine kinase domain of epidermal growth factor receptor (EGFR) is a decisive factor for the therapeutic response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma. The stability of mutant EGFR is maintained by various regulators, including heat shock protein 90 (Hsp90). The C terminus of Hsc70-interacting protein (CHIP) is a Hsp70/Hsp90 co-chaperone and exhibits E3 ubiquitin ligase activity. The high-affinity Hsp90-CHIP complex recognizes and selectively regulates their client proteins. CHIP also works with its own E3 ligase activity independently of Hsp70/Hsp90. Here, we investigated the role of CHIP in regulating EGFR in lung adenocarcinoma and also evaluated the specificity of CHIP's effects on mutant EGFR. In HEK 293T cells transfected with either WT EGFR or EGFR mutants, the overexpression of CHIP selectively decreased the expression of certain EGFR mutants (G719S, L747_E749del A750P and L858R) but not WT EGFR. In a pull-down assay, CHIP selectively interacted with EGFR mutants and simultaneously induced their ubiquitination and proteasomal degradation. The expressions of mutant EGFR in PC9 and H1975 were diminished by CHIP, while the expression of WT EGFR in A549 was nearly not affected. In addition, CHIP overexpression inhibited cell proliferation and xenograft's tumor growth of EGFR mutant cell lines, but not WT EGFR cell lines. EGFR mutant specific ubiquitination by CHIP may provide a crucial regulating mechanism for EGFR in lung adenocarcinoma. Our results suggest that CHIP can be novel therapeutic target for overcoming the EGFR TKI resistance.

Production of transgenic cloned mini-pigs expressing Human Leukocyte Antigen-G1(HLA-G1) gene by Nuclear Transfer

Park, K.W.,Hang, G.S.,Hong, S.P.,Choi, K.M.,Lee, S.H.,Yoo, J.Y.,Heo, K.N.,Jin, D.I.,Park, C.S.,Seol, J.G. 충남대학교 형질전환복제돼지연구센터 2007 논문집 Vol. No.10

Production of transgenic cloned mini-pigs expressing Human Leukocyte Antigen-G1(HLA-G1) gene by Nuclear Transfer

Park K.W.,Han G.S.,Hong S.P.,Choi K.M.,Lee S.H.,Yoo J.Y.,Heo K.N.,Jin D.I.,Park C.S.,Seol J.G. 한국발생생물학회 2005 한국발생생물학회 학술발표대회 Vol.2005 No.1

Effect of exercise training on A-FABP, lipocalin-2 and RBP4 levels in obese women

Choi, K. M.,Kim, T. N.,Yoo, H. J.,Lee, K. W.,Cho, G. J.,Hwang, T. G.,Baik, S. H.,Choi, D. S.,Kim, S. M. Blackwell Publishing Ltd 2009 Clinical endocrinology Vol.70 No.4

<P>Summary</P><P>Objective </P><P>Lipocalin family proteins, including adipocyte fatty acid-binding protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently been identified as novel adipokines associated with obesity, type 2 diabetes and the metabolic syndrome. We have evaluated the effect of exercise training on lipocalin family proteins and inflammatory markers.</P><P>Study subjects </P><P>Thirty obese Korean women and 15 age-matched nonobese control subjects were studied.</P><P>Design </P><P>Concentrations of the lipocalin family proteins were compared between obese and nonobese women and were evaluated before and 3 months after an exercise programme consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength training (20 min/session, 100 kcal/day) five times a week.</P><P>Results </P><P>Obese women exhibited higher A-FABP levels compared to nonobese women (21·4 ± 6·4 µg/l <I>vs.</I> 13·6 ± 4·4 µg/l, <I>P</I> < 0·001). However, neither lipocalin-2 nor RBP4 levels were significantly different between the two groups, although the difference in lipocalin-2 was marginally significant (<I>P</I> = 0·054). Circulating A-FABP levels were significantly associated with body mass index (BMI), waist circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high-sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise training programme, serum A-FABP levels decreased significantly from 21·4 ± 6·4 µg/l to 19·3 ± 6·8 µg/l (<I>P</I> = 0·038), along with a reduction in weight, BMI, waist circumference, fasting glucose and total cholesterol levels. There was no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels increased after the exercise programme.</P><P>Conclusion </P><P>Exercise training with weight loss induced a significant reduction in circulating A-FABP levels in obese Korean women.</P>

Combinatorial biosynthesis and antibacterial evaluation of glycosylated derivatives of 12-membered macrolide antibiotic YC-17

Shinde, P.B.,Han, A.R.,Cho, J.,Lee, S.R.,Ban, Y.H.,Yoo, Y.J.,Kim, E.J.,Kim, E.,Song, M.C.,Park, J.W.,Lee, D.G.,Yoon, Y.J. Elsevier Science Publishers 2013 Journal of biotechnology Vol.168 No.2

Expression plasmids carrying different deoxysugar biosynthetic gene cassettes and the gene encoding a substrate-flexible glycosyltransferase DesVII were constructed and introduced into Streptomyces venezuelae YJ003 mutant strain bearing a deletion of a desosamine biosynthetic (des) gene cluster. The resulting recombinants produced macrolide antibiotic YC-17 analogs possessing unnatural sugars replacing native d-desosamine. These metabolites were isolated and further purified using chromatographic techniques and their structures were determined as d-quinovosyl-10-deoxymethynolide, l-rhamnosyl-10-deoxymethynolide, l-olivosyl-10-deoxymethynolide, and d-boivinosyl-10-deoxymethynolide on the basis of 1D and 2D NMR and MS analyses and the stereochemistry of sugars was confirmed using coupling constant values and NOE correlations. Their antibacterial activities were evaluated in vitro against erythromycin-susceptible and -resistant Enterococcus faecium and Staphylococcus aureus. Substitution with l-rhamnose displayed better antibacterial activity than parent compound YC-17 containing native sugar d-desosamine. The present study on relationships between chemical structures and antibacterial activities could be useful in generation of novel advanced antibiotics utilizing combinatorial biosynthesis approach.

Absorption Rates and Capacities of CO~2 into Aqueous Mixtures of Methyldiethanolamine(MDEA) and Hexamethylenediamine(HMDA)

Rho, S.-W 한국화학공학회 1997 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.35 No.5

7일령 조기 이유자돈에 대한 액상사료 자동급이기 이용효과

유용희,정일병,장병귀,문홍길,김태일,한정대,박홍석 한국동물자원과학회 2003 한국축산학회지 Vol.45 No.6

This study was conducted to test the efficacy of the automatic liquid feeder(designated as NLRI) developed by National Livestock Research Institute, Korea foe 7-day old early-weaning piglets. The other automatic liquid feeder imported from USA(designated as IALF) was used for a comparative purpose. A total of sixty piglets of 7 days of age were allotted to three treatments. The control group of 20 piglets was raised by their own sows until 21 days of age, while others were shifted to automatic liquid feeders of either NLRI or IALF on 7 days of age and reared during 14 days post-weaning. After then, all the piglets were fed nutritionally identical mash diets until 70 days of age. Compared with control group, body weight of piglets reared on automatic liquid feeders were lighter(P<0.05) at 21 days of age [5.55㎏ (control) vs 4.97 (NLRI) and 4.98㎏ (LALF)], while heavier(p<0.05 at 70days of age(24.82㎏ vs 30.17 and 29.42㎏). The results indicated that pigs reared on liquid feeding showed higher(P<0.05) average daily gain than control pigs during the whole experimental period [346.7㎏ (control) vs 425.8 (NLRI) and 416.1g (LALD)], while no difference was found in feed/gain (1.67 vs 1.78 and 1.84). There was no difference in growth performance and incidence of diarrhea between two automatic liquid feeders, NLRI and LALF. Compared with control group, intestinal villi tended to be shorter in liquid feeding group during the first week, but were recovered within two weeks. The results suggest that the automatic liquid feeder newly developed by National Livestock Research Institute, Korea can be successfully used for rearing young piglets weaned at very early age.

직관에서 점성유체 유동의 압력파 전달특성

나기대,유영태,모양우,김형오 朝鮮大學校 機械技術硏究所 1999 機械技術硏究 Vol.2 No.2

In this paper, the accurate control of dynamic power greatly influences on the efficiency, stability and economy of equipment, according as the mechanical facilities are becoming highly efficient, precise and automatic in the industry field. The pulsatory flowing appears in the field of engineering and science and technology like pipe line, power control system of machine equipment and blood flowing etc. We compared the frequency characteristics in the oil with water, when changed the frequency in the pipe also we simulated the theoretical equation to computer. According to frequency increase in this paper under the influence, wave form of velocity in pulsating flow and viscosity are drop. Coefficient of viscosity become Increase so that impedance and resistance are increase. The system can be modeled as a L-R-C series circuit with the resistance affected by signal frequency and amplitude.