Suppression of c-Myc induces apoptosis via an AMPK/mTOR-dependent pathway by 4-O-methyl-ascochlorin in leukemia cells

Shin, J. M.,Jeong, Y. J.,Cho, H. J.,Magae, J.,Bae, Y. S.,Chang, Y. C. Springer Science + Business Media 2016 Apoptosis Vol.21 No.5

<P>4-O-Methyl-ascochlorin (MAC) is a methylated derivative of the prenyl-phenol antibiotic ascochlorin, which was isolated from an incomplete fungus, Ascochyta viciae. Although the effects of MAC on apoptosis have been reported, the underlying mechanisms remain unknown. Here, we show that MAC promoted apoptotic cell death and downregulated c-Myc expression in K562 human leukemia cells. The effect of MAC on apoptosis was similar to that of 10058-F4 (a c-Myc inhibitor) or c-Myc siRNA, suggesting that the downregulation of c-Myc expression plays a role in the apoptotic effect of MAC. Further investigation showed that MAC downregulated c-Myc by inhibiting protein synthesis. MAC promoted the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR) and its target proteins, including p70S6 K and 4E-BP-1. Treatment of cells with AICAR (an AMPK activator), rapamycin (an mTOR inhibitor), or mTOR siRNA downregulated c-Myc expression and induced apoptosis to a similar extent to that of MAC. These results suggest that the effect of MAC on apoptosis induction in human leukemia cells is mediated by the suppression of c-Myc protein synthesis via an AMPK/mTOR-dependent mechanism.</P>

발화합성용액의 pH가 Y₁Ba₂Cu₃O_7-x 초전도상 생성 속도에 미치는 영향

박정식,김영순,양석우,김춘영,신형식,Park, J.S.,Kim, Y.S.,Yang, S.W.,Kim, C.Y.,Shin, H.S. 한국공업화학회 1998 공업화학 Vol.9 No.2

$Y_2O_3$(99.9%)와 $BaCO_3$(99.9%) 및 CuO(99.9%)를 사용하여 $Y_1Ba_2Cu_3O_{7-x}$(123) 분말을 발화합성법에 의해 제조하였다. 발화전 용액을 여러 가지 pH로 변화시켜 제조하였으며, 이 분말을 성형하여 열처리 온도와 시간 변화에 따른 상형성과 반응특성을 조사하였다. 시료의 조성과 조직의 특성은 ICP와 SEM을 이용하여 측정하였고, Y-Ba-Cu-O계의 상형성과 전화율을 결정하기 위해 X선 회절분석을 하였다. 발화합성법을 이용하여 pH 7(${\pm}0.3$)에서 제조된 123 분말이 순도와 균일성 및 반응특성에서 가장 좋은 결과를 보였다. pH 7(${\pm}0.3$)에서 제조된 분말을 이용한 123 상생성에 따른 활성화에너지(${\Delta}E_a$)는 191kJ/mol으로서 고상반응법의 230kJ/mol에 약 13% 정도 더 낮았다. The $Y_1Ba_2Cu_3O_{7-x}$(123) superconductor powders were prepared by pyrophoric synthesis method(PSM) using $Y_2O_3$(99.9%), $BaCO_3$(99.9%), and CuO(99.9%) powders. The phase formation and reaction kinetics of 123 superconductor manufactured with powders prepared in various pHs of pyrophoric synthetic solution have been studied through the experiments at various heat treatment temperatures and times. Inductively coupled plasma(ICP) spectroscopy and scanning electron microscopy(SEM) measurements were performed to examine the composition and morphology of the sample. X-ray diffraction(XRD) analysis was done to determine phase formation and conversion ratio of Y-Ba-Cu-O systems. The 123 powder prepared at pH 7(${\pm}0.3$) yields the best result in terms of purity, homogeneity, and reactivity. The activation energies(${\Delta}E_a$) of 123 phase formation were found to be 191 kJ/mol and 230kJ/mol in solid state reaction method and pyrophoric synthesis method, respectively.

발화합성용액의 pH 가 Y1Ba2Cu3O7-x 초전도상 생성 속도에 미치는 영향

박정식,김영순,양석우,김춘영,신형식 ( J . S . Park,Y . S . Kim,S . W . Yang,C . Y . Kim,H . S,Shin ) 한국공업화학회 1998 공업화학 Vol.9 No.2

Y₂O₃(99.9%)와 BaCO₃(99.9%) 및 CuO(99.9%)를 사용하여 Y₁Ba₂Cu₃O_(7-x)(123) 분말을 발화합성법에 의해 제조하였다. 발화전 용액을 여러 가지 pH로 변화시켜 제조하였으며, 이 분말을 성형하여 열처리 온도와 시간 변화에 따른 상형성과 반응특성을 조사하였다. 시료의 조성과 조직의 특성은 ICP와 SEM을 이용하여 측정하였고, Y-Ba-Cu-O계의 상형성과 전화율을 결정하기 위해 X선 회절분석을 하였다. 발화합성법을 이용하여 pH 7(±0.3)에서 제조된 123 분말이 순도와 균일성 및 반응특성에서 가장 좋은 결과를 보였다. pH 7(±0.3)에서 제조된 분말을 이용한 123 상생성에 따른 활성화에너지(ΔE_n)는 191 kJ/mol으로서 고상반응법의 230 kJ/mol에 약 13% 정도 더 낮았다. The Y₁Ba₂Cu₃O_(7-x)(123) superconductor powders were prepared by pyrophoric synthesis method(PSM) using Y₂O₃(99.9%), BaCO₃(99.9%), and CuO(99.9%) powders. The phase formation and reaction kinetics of 123 superconductor manufactured with powders prepared in various pHs of pyrophoric synthetic solution have been studied through the experiments at various heat treatment temperatures and times. Inductively coupled plasma(ICP) spectroscopy and scanning electron microscopy(SEM) measurements were performed to examine the composition and morphology of the sample. X-ray diffraction(XRD) analysis was done to determine phase formation and conversion ratio of Y-Ba-Cu-O systems. The 123 powder prepared at pH 7(±0.3) yields the best result in terms of purity, homogeneity, and reactivity. The activation energies(ΔE_n) of 123 phase formation were found to be 191 kJ/mol and 230 kJ/mol in solid state reaction method and pyrophoric synthesis method, respectively.

Evaluating the PM damage cost due to urban air pollution and vehicle emissions in Seoul, Korea

Lee, Y.J.,Lim, Y.W.,Yang, J.Y.,Kim, C.S.,Shin, Y.C.,Shin, D.C. Academic Press 2011 Journal of environmental management Vol.92 No.3

This study evaluated the prospective damage costs of PM<SUB>2.5</SUB> inhalation. We performed a health risk assessment based on an exposure-response function to estimate the annual population risk in the Seoul metropolitan city, Korea. Also, we estimated a willingness-to-pay (WTP) amount for reducing the mortality rate in order to evaluate a statistical life value. We combined the annual population risk and the value-of-statistical-life to calculate the damage cost estimate. In the health risk assessment, we applied the PM<SUB>2.5</SUB> relative risk to evaluate the annual population risk. We targeted an exposure population of 5,401,369 persons who were over the age of 30. Using a Monte-Carlo simulation for uncertainty analysis, we estimated that the population risk of PM<SUB>2.5</SUB> inhalation during a year in Seoul is 2181 premature deaths for acute exposure and 18,510 premature deaths for chronic exposure. The monthly average WTP for 5/1000 mortality reduction over ten years is $20.20 USD (95% C.I: $16.60-24.50) and the implied value-of-statistical-life (VSL) is $485,000 USD (95% C.I: $398,000-588,000). The damage cost estimate due to risk from PM<SUB>2.5</SUB> inhalation in Seoul is about $1057 million USD per year for acute exposure, and $8972 million USD per year for chronic exposure. It is important to note that this cost estimate does not reflect all health damage cost estimates in this urban area. This recommendation is a model for evaluating a mortality risk reduction and as such we must re-evaluate an integrated application of morbidity risk.

Diamond 박막 성장에 미치는 Si 표면 영향의 AES에 의한 연구

이철로(C. R. Lee),신용현(Y. H. Shin),임재영(J. Y. Leem),정광화(K. H. Chung),천병선(B. S. Chun) 한국진공학회(ASCT) 1993 Applied Science and Convergence Technology Vol.2 No.2

Si 기판 표면상태 변화와 관련된 핵생성 자유에너지 증가에 따른 다이아몬드 박막성장 거동을 관찰하였다. 표면 연마조건 변화에 따른 3가지 기판(A-Si, B-Si, C-Si) 위에 동일한 성장조건으로 다이아몬드를 성장하였으며, 이때 형상인자와 관련된 자유에너지 관계는 ΔG_(A-Si)<ΔG_(B-Si)<ΔG_(C-Si)이다. AES, SEM, XRD, RHEED에 의해 각각의 박막 A, B, C를 조사한 결과, 핵생성 자유에너지가 가장 적은 A 박막은 (100) (110) 면이 지배적인 고품위 다이아몬드 박막이다. 자유에너지가 A에 비해 다소 적은 B 박막은 (111) 면이 지배적인 8면체 다이아몬드 박막이고, 자유에너지가 가장 적은 C 박막은 흑연이 많이 함유된 구상의 다이아몬드이다. The effect of nucleation free energy related to Si surface states on diamond film growth behavior has been studied. At first, the three kinds of diamond thin films (A, B, C) were deposited on various Si substrates (A-Si, B-Si, C-Si) whose surfaces were polished with 1 ㎛ diamond paste, 6 ㎛ Al₂O₃ powder and 12 ㎛ Al₂O₃ powder respectively. And then, relative nucleation free energy calculated is ΔG_(A-Si)<ΔG_(B-Si)<ΔG_(c-Si) Although there are some difference in grain size, shape and nucleation site, the thin films on A-Si and B-Si were diamond including a small amount of DLC which was confirmed by AES, SEM, XRD and RHEED. Namely, the diamonds of films (B) were not nucleated in scratches but in dents and larger in grain size compare with the film (C) of which diamond were nucleated not only scratches but also dents. And, the sphere diamond which is not general shape was grown on C-Si. After all, the sphere was turned out to be the diamond including much graphite as a result of the AES in situ depth profiling. Consequently, the diamond shape and quality grown on Si were changed from the crystal which the (100) and (110) planes were predominent to the crystal in which (111) plane was predominent, and next to sphere shape diamond including much graphite according as the nucleation free energy increases.

Intramolecular energy flow and bond dissociation in iodoacetylene and iododiacetylene

Ree,J.,Shin,H. K,Lee,C. S.,Kim,Y.H. 國立昌原大學校 基礎科學硏究所 1994 基礎科學硏究所論文集 Vol.6 No.-

Intermolecular and intramolecular energy flow and subsequent bond dissociation in collinear collisions Ⅰ-C≡C-H+Ar and Ⅰ-C≡C-C≡C-H+Ar have been studied by classical trajectory techniques over the collision energy range of 0 to 10 eV. When the molecule is initially in the ground state, the overall energy transfer in Ⅰ-C≡C-H+Ar is very small, but in Ⅰ-C≡C-C≡C-H+Ar it is large. The collisionally perturbed C-H bond stores a large amount of energy from translation for a brief period during the early stage of collision and transfers most of it to the inner region of the molecule, specifically to the low frequency C-I vibration. Thus the high-frequency vibration of the perturbed C-H bond during the collision plays a crucial role in determining the extent of intramolecular energy transfer and, in turn, C-I dissociation. But in nondissociative collisions, there is another series of the C-H vibration at the latter stage of collision. transferring energy back to translation. This study also considers collision-induced intramolecular energy flow in the molecule with an initially excited C-H bond. The relaxation of the low-lying C-H excitation is significantly weakened, thus becoming comparable to that of the triple bond, in which case the isolating effect of the adjacent C≡C bond is no longer important and intramolecular energy flow becomes efficient.

SIGN-R1, a C-type lectin, enhances apoptotic cell clearance through the complement deposition pathway by interacting with C1q in the spleen

Prabagar, M G,Do, Y,Ryu, S,Park, J-Y,Choi, H-J,Choi, W-S,Yun, T J,Moon, J,Choi, I-S,Ko, K,Ko, K,Young Shin, C,Cheong, C,Kang, Y-S Macmillan Publishers Limited 2013 Cell death and differentiation Vol.20 No.4

Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1–C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-β in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

SIGN-R1, a C-type lectin, enhances apoptotic cell clearance through the complement deposition pathway by interacting with C1q in the spleen

MG Prabagar,Y Do,S Ryu,J-Y Park,H-J Choi,W-S Choi,TJ Yun,J Moon,I-S Choi,K Ko,K Ko,C Young Shin,C Cheong,Y-S Kang 한국당과학회 2013 한국당과학회 학술대회 Vol.2013 No.1

Complements, such as C1q and C3, and macrophages in the splenic marginal zone (MZMs) play pivotal roles in the efficient uptake and processing of circulating apoptotic cells. SIGN-R1, a C-type lectin that is highly expressed in a subpopulation of MZMs, regulates the complement fixation pathway by interacting with C1q, to fight blood-borne Streptococcus pneumoniae. Therefore, we examined whether the SIGN-R1-mediated classical complement pathway plays a role in apoptotic cell clearance and immune tolerance. SIGN-R1 first-bound apoptotic cells and this binding was significantly enhanced in the presence of C1q. SIGN-R1-C1q complex then immediately mediated C3 deposition on circulating apoptotic cells in the MZ, leading to the efficient clearance of them. SIGN-R1-mediated C3 deposition was completely abolished in the spleen of SIGN-R1 knockout (KO) mice. Given that SIGN-R1 is not expressed in the liver, we were struck by the finding that C3-deposited apoptotic cells were still found in the liver of wild-type mice, and dramatically reduced in the SIGN-R1 KO liver. In particular, SIGN-R1 deficiency caused delayed clearance of apoptotic cells and aberrant secretion of cytokines, such as TNF-α, IL-6, and TGF-β in the spleen as well as in the liver. In addition, anti-double- and single-stranded DNA antibody level was significantly increased in SIGN-R1-depleted mice compared with control mice. These findings suggest a novel mechanism of apoptotic cell clearance which is initiated by SIGN-R1 in the MZ and identify an integrated role of SIGN-R1 in the systemic clearance of apoptotic cells, linking the recognition of apoptotic cells, the opsonization of complements, and the induction of immune tolerance.

Role of Leu188 in the Fatty Acid Hydroxylase Activity of CYP102A1 from Bacillus megaterium

Jang, H.H.,Shin, S.M.,Ma, S.H.,Lee, G.Y.,Joung, Y.H.,Yun, C.H. Elsevier 2016 Journal of molecular catalysis Enzymatic Vol.133 No.-

<P>P450 BM3 (CYP102A1) from Bacillus megaterium catalyzes the subterminal hydroxylation of fatty acids with 12-22 carbons at the omega-1, omega-2 and omega-3 positions. Several amino acids located at the substrate channel and active sites are known to be important for the catalytic activity of CYP102A1. The L188 residue at the C-terminus of alpha-helix F undergoes a large shift upon substrate binding and has frequently been found in different combinations of multiple mutations showing enhanced and altered activities. In this study, we examined the role of the L188 residue by comparing the catalytic activities of wild-type CYP102A1 and 19 mutants of L188. The mutants were made with site-directed mutagenesis and functionally expressed in Escherichia coll. The enzymatic properties of the mutants for a set of fatty acids (C-10-C-16) were compared to the properties of the wild-type. L188Q and L188 P mutants showed especially strong increases in hydroxylase activity toward C-10-C-13 fatty acids, although they did not have activity changes for C-14-C-16 fatty acids. Although most mutants showed very similar overall hydroxylation rates for myristic acid, 14 mutants showed apparent changes in the regioselectivity of hydroxylation with a preference for the omega-3 position over the omega-1 position. A possible role for the L188 residue has been discussed in the context of the structure and function of CYP102A1. (C) 2016 Elsevier B.V. All rights reserved.</P>

주성분 분석을 이용한 거세한우의 체형분류에 관한 연구

하동우,김현철,김병우,이문연,이종헌,신철교,도창희,이정규 한국동물자원과학회 2002 한국축산학회지 Vol.44 No.6

1997년부터 2001년까지 (사)한국종축개량협회의 전국한우능력평가대회에 출품된 642두의 거세한우의 도축 전까지 4회에 걸쳐 주요 10개 부위의 체형 측정치를 조사하여 주성분 분석을 이용하여 체형을 분류하였으며, 각 체형 측정치의 주성분 지수와 도체 형질과의 상관관계를 분석하였으며, 그 결과를 요약하면 다음과 같다. 1. 1차, 2차, 3차 및 4차 체형 측정치의 principal component(이하 P.C) 1의 분산은 각각 7.610, 8.297, 7.269 및 5.736로서 전체분산 중 76.0%, 83.0%, 72.7% 및 57.4%를 나타낼 수 있었고, P.C 1, P.C 2, P.C 3의 합은 전체분산 중 각각 86.69%, 90.49%, 84.62% 및 77.26%를 나타났다. 2. 각 차수별 체형 측정치의 P.C 1의 모든 계수가 양(+)이어서 일반적으로 좋은 체구의 크기를 나타내었으며, 체구의 크기에 가장 크게 영향을 미치는 형질은 흉심(0.328∼0.339)과 요각폭(0.325∼0.341)이였다. 또한 P.C 2, P.C 3 및 P.C 4는 각 차수별로 다양하게 나타났다. 3. 1차, 2차, 3차 및 4차 체형 측정치의 주성분 지수들과 도체형질간의 상관계수 추정에서 대부분의 분산을 차지하는 P.C 1은 도체중(0.539∼0.755), 일당증체량(0.256∼0.564), 등지방두께(0.227∼0.280) 및 배최장근단면적(0.187∼0.344)간에 정(+)의 상관을 보였으며, 육량지수(-0.246∼-0.110)와는 부(-)의 상관을 보였고, 근내지방도(0.066∼0.099)와는 대부분 유의적인 상관을 보이지 않거나 낮은 상관을 보였고, P.C 2, P.C 3 및 P.C 4는 주성분 지수들의 값에 따라 도체형질과 다양한 상관관계를 보였다. 단일 체형형질과 도체형질간의 상관 그리고 P.C 1의 주성분 지수와 도체형질과의 상관간에는 큰 차이가 없었다. Data were consisted of the ten body measurements (withers height, rump height, body length, chest depth, chest width, rump width, rump length, thurls width, hipbone width and chest girth) of 642 steers (Korean cattle), which was entered in the National Beef Quality Contest hosted by the Korea Animal Improvement Association from 1997 to 2001. A principal components analysis was used to classify the body types of the steers, and estimate the correlations between carcass traits and principal components for the body measurements of the first, second, third and fourth period, respectively. The first principal component of body measurements at the first, second, third and fourth period accounted for 76.0%, 83.0%, 72.7% and 57.4% of the total variance, respectively. The sum of first, second and third principal component at each period accounted for 86.69%, 90.49%, 84.62% and 77.26% of the total variance, respectively. At each period, all the first principal component of the body measurements were positive and it generally showed large framed body shape. The size of body was influenced mostly by chest depth(0.328∼0.339) and rump length(0.325∼0.341). The second, third and fourth principal component at the each period were various. There were positive correlations between principal components index of each period and carcass traits such as carcass weight(0.539∼0.755), average daily gain(0.256∼0.564), backfat thickness(0.227∼0.280), and eye muscle area(0.187∼0.344). The correlation with yield grade index(-0.246∼-0.110), however, was negative. The correlation with marbling score(0.066∼0.099) was low or statistically insignificant. According to principal component indexes of the second, third, and fourth components, the correlations with the carcass traits were various. There were no large differences between the correlations of the single body measurement trait with the carcass traits and the correlations of the first principal component indexes with the carcass traits.