• Title/Summary/Keyword: Rac3

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Silencing of Rac3 Inhibits Proliferation and Induces Apoptosis of Human Lung Cancer Cells

  • Liu, Tie-Qin;Wang, Ge-Bang;Li, Zheng-Jun;Tong, Xiang-Dong;Liu, Hong-Xu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.3061-3065
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    • 2015
  • Background: Rac3, a member of the Rac family of small guanosine triphosphatases (GTPases), regulates a variety of cell functions, including the organization of the cytoskeleton, cell migration, and invasion. Overexpression of Rac3 has been reported in several human cancers. However, the role of Rac3 in lung cancer (LC) has not been determined in detail. The purpose of this study was to investigate the effect of silencing of Rac3 expression in human LC cells and the consequences for cell survival. Materials and Methods: Lentivirus small hairpin RNA (shRNA) interference techniques were utilized to knock down the Rac3 gene. Gene and protein expression was quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. LC cell apoptosis was examined by annexin V-APC /propidium iodide staining. Results: Efficient silencing of Rac3 strongly inhibited A549 cell proliferation and colony formation ability, and significantly decreased tumor growth. Moreover, flow cytometry analysis showed that knockdown of Rac3 led to G2/M phase cell cycle arrest as well as an excess accumulation of cells in the G1 and S phase. Conclusions: Thus, functional analysis using shRNAs revealed a critical role for Rac3 in the tumor growth of LC cells. shRNA silencing of Rac3 could provide an effective strategy to treat LC.

Rac1 inhibition protects the kidney against kidney ischemia/reperfusion through the inhibition of macrophage migration

  • You Ri Park;Min Jung Kong;Mi Ra Noh;Kwon Moo Park
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.3
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    • pp.257-265
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    • 2023
  • Kidney ischemia/reperfusion (I/R) injury, a common cause of acute kidney injury (AKI), is associated with the migration of inflammatory cells into the kidney. Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho family of small GTPase, plays an important role in inflammatory cell migration by cytoskeleton rearrangement. Here, we investigated the role of Rac1 on kidney I/R injury and macrophage migration. Male mice were subjected to either 25 min of bilateral ischemia followed by reperfusion (I/R) or a sham operation. Some mice were administrated with either NSC23766, an inhibitor of Rac1, or 0.9% NaCl (vehicle). Kidney damage and Rac1 activity and expression were measured. The migration and lamellipodia formation of RAW264.7 cells, mouse monocyte/macrophage, induced by monocyte chemoattractant protein-1 (MCP-1, a chemokine) were determined using transwell migration assay and phalloidin staining, respectively. In sham-operated kidneys, Rac1 was expressed in tubular cells and interstitial cells. In I/R-injured kidneys, Rac1 expression was decreased in tubule cells in correlation with the damage of tubular cells, whereas Rac1 expression increased in the interstitium in correlation with an increased population of F4/80 cells, monocytes/macrophages. I/R increased Rac1 activity without changing total Rac1 expression in the whole kidney lysates. NSC23766 administration blocked Rac1 activation and protected the kidney against I/R-induced kidney damage and interstitial F4/80 cell increase. NSC23766 suppressed monocyte MCP-1-induced lamellipodia and filopodia formation and migration of RAW 264.7 cells. These results indicate Rac1 inhibition protects the kidney against I/R via inhibition of monocytes/macrophages migration into the kidney.

Determining the Number of Risk Level Using Real-time Sensitivities in the Probabilistic Maritime Risk Evaluation (확률기반 해상위기평가에서 실시간 민감도를 이용한 위기수준의 단계 구분 수 결정에 관한 연구)

  • Gang, Sang-Guen
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.20 no.6
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    • pp.685-691
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    • 2014
  • The result of probabilistic maritime risk evaluation is represented by the probability(P=0.0~1.0) These results are shown by an index using Risk Acceptance Criteria(RAC) to base the evaluation generally to know the risk level easily. Current RAC is divided into 3 steps, 5 steps, 7 steps, etc. Despite need to evaluate whether the number of RAC for risk evaluation is reasonable, there is not a related research yet. In this study, It was proposed the evaluation method to determine the optimum index number of RAC using the Sensitivity distribution characteristics and the Sensitivity by the index number of RAC. As application result from the proposed method for probabilistic risk evaluation data obtained from the prior studies, It could be determined the optimum index number of RAC by Sensitivity below 10 times and confirmed that the proposed method is reasonable by this study.

Roles of PI3K and Rac Pathways in H-ras Induced Invasion and Motility

  • Ilchung Shin;Kim, Seonhoe;Aree Moon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.144-144
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    • 2003
  • Phosphatidylinositol 3-kinase (PI3K) and Rac play important roles that regulate cellular functions including cell survival and .migration. In the present study, we investigated the functional roles of PI3K and Rac1 pathways in H-ras-induced invasive phenotype and motility of MCF10A cells.(omitted)

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Chemical Reactivity between Ni(II)-Macrocycle Complex Ions ($NiL_m{^{2+}}$) and $CN^-$ (Ni(II)-거대고리 리간드 착이온 ($NiL_m{^{2+}}$) 과 $CN^-$ 이온간의 반응성)

  • Yu-Chul Park;Jong-Chul Byun
    • Journal of the Korean Chemical Society
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    • v.31 no.4
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    • pp.334-343
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    • 1987
  • The Chemical reactions between $NiL_m{^{2+}}\{$Ni(rac-1[14]7-diene)^{2+},\;Ni(meso-1[14]7-diene)^{2+},\;Ni(1[14]4-diene)^{2+},\;{\alpha}-Ni(rac-[14]-decane)^{2+},\;{\beta}-Ni(rac-[14]-decane)^{2+},\;and\;Ni(meso-[14]-decane)^{2+}$}\and\ CN^-$ ion were studied by the spectrophotometric method. The equilibrium constants (K_1$) for the 1:1 complex ion, $[NiL_m(CN)]^+\;with\;NiL_m{^{2+}}\;and\;CN^-$ ion were determined in the range of 3 to $25^{\circ}C$. The $K_1\;for\;Ni(rac-1[14]7-diene)^{2+},\;Ni(meso-1[14]7-diene)^{2+},\;Ni(1[14]4-diene)^{2+},\;{\alpha}-Ni(rac-[14]-decane)^{2+},\;{beta}-Ni(rac-[14]-decane)^{2+},\;and\;Ni(meso-[14]-decane)^{2+}\;at\;15^{\circ}C$ was 4.7, 5.3, 6.2, 7.5, 9.4, and 9.8, respectively. The values of $K_1$ decreased with increasing temperature. From the temperature effect on equilibrium constant ($K_1$), thermodynamic parameters $({\Delta}H^{\circ},\;{\Delta}S^{\circ},\;{\Delta}G^{\circ})$ for reaction were evaluated and the reaction of $NiL_m{^{2+}}\;and\;CN^-$ ion was exothermic. $NiL_m{^{2+}\;reacts\;with\;CN^-$ ion to give $Ni(CN)_4{^{2-}}$ ion and macrocyclic ligand $(L_m)$. The kinetics of formation of the $Ni(CN)_4{^{2-}}$ ion of varying the $[CN^-],\;[HCN],\;and\;[OH^-]$ have been investigated at 3∼$25^{\circ}C\;and\;0.5M\;NaClO_4$. Maintaining a constant $[CN^-],\;k_{obs}/[CN^-]^2$ increases linearly with increasing [HCN]. In the presence of large quantities of $[OH^-],\;k_{obs}/[CN^-]^2$ also increases linearly with $[OH^-]$. From the temperature effect on kinetic constant (k_{obs})$, parameter of activation $({\Delta}H^{\neq},\;{\Delta}S^{\neq})$ of reaction of $NiL_m{^{2+}}\;with\;CN^-$ ion were determined. For the $Ni(rac-1[14]7-diene)^{2+},\;Ni(meso-1[14]7-diene)^{2+},\;{\alpha}-Ni(rac-[14]-decane)^{2+},\;{\beta}-Ni(rac-[14]-decane)^{2+},\;and\;Ni(meso-[14]-decane)^{2+}\;series\;{\Delta}H^{\neq}$ gradually decrease as the d-d transition energy, $ν(cm^{-1})$ decrease. And the reaction of the five $NiL_m{^{2+}}\;with\;CN^-$ ion take place by way of equal paths.

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Seismic Analysis on Recycled Aggregate Concrete Frame Considering Strain Rate Effect

  • Wang, Changqing;Xiao, Jianzhuang;Sun, Zhenping
    • International Journal of Concrete Structures and Materials
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    • v.10 no.3
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    • pp.307-323
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    • 2016
  • The nonlinear behaviors of recycled aggregate concrete (RAC) frame structure are investigated by numerical simulation method with 3-D finite fiber elements. The dynamic characteristics and the seismic performance of the RAC frame structure are analyzed and validated with the shaking table test results. Specifically, the natural frequency and the typical responses (e.g., storey deformation, capacity curve, etc.) from Model 1 (exclusion of strain rate effect) and Model 2 (inclusion of strain rate effect) are analyzed and compared. It is revealed that Model 2 is more likely to provide a better match between the numerical simulation and the shaking table test as key attributes of seismic behaviors of the frame structure are captured by this model. For the purpose to examine how seismic behaviors of the RAC frame structure vary under different strain rates in a real seismic situation, a numerical simulation is performed by varying the strain rate. The storey displacement response and the base shear for the RAC frame structure under different strain rates are investigated and analyzed. It is implied that the structural behavior of the RAC frame structure is significantly influenced by the strain rate effect. On one hand, the storey displacements vary slightly in the trend of decreasing with the increasing strain rate. On the other hand, the base shear of the RAC frame structure under dynamic loading conditions increases with gradually increasing amplitude of the strain rate.

Polymerization of $\alpha$-Olefin Catalyzed by rac-(EBI) M($NMe_2$)$_2$(M=Zr, Hf)/$AlR_3$/[$Ph_3C$][$B(C_{6}F_{5})$)$_4$] (rac-(EBI) M($NMe_2$)$_2$(M=Zr, Hf)/$AlR_3$/[$Ph_3C$[$B(C_{6}F_{5})$)$_4$ 촉매를 이용한 $\alpha$-올레핀의 중합)

  • Kim, Il;Choi, Chang-Soo;Kim, Ki-Tae
    • Polymer(Korea)
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    • v.24 no.5
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    • pp.646-655
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    • 2000
  • Polymerizations of higher $\alpha$-olefins were carried out in toluene by using highly isospecific catalyst, rac-(EBI)M(NMe$_2$)$_2$ (EBI=1,2-ethylenebis-(1-indenyl); M=Zr(rac-1); M=Hf(rac-2)) In the presence of Al(i-Bu)$_3$/[Ph$_3$C][B($C_{6}F_{5}$)$_4$]. The polymerization of high $\alpha$-olefin showed high activity and similar polymerization behavior. The polymerization activity was affected by both monomer size and lateral size of polymer chain. The conversion of monomer to polymer decreases with the increased lateral size in the order of 1-pentene>1-hexene>1-octene>1-decene. The same dependences of melting behavior and intrinsic viscosity of polyolefin on lateral size were observed according to the results obtained by differential scanning calorimetry and intrinsic viscosity. All poly($\alpha$-olefin)s showed very high isotacticity (triad) and the isotacticity increases in the order of poly(1-pentene)$^1H$ NMR and Raman spectra analysis showed that chain transfer to cocatalyst, which generates saturated methyl groups, Is a main chain termination. The $\beta$-hydride eliminations, which generate unsaturated vinylidene, tri-substituted, and vinylene end group. are found to be minor chain terminations.

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Regulation of Nrf2 Transactivation Domain Activity by p160 RAC3/SRC3 and Other Nuclear Co-Regulators

  • Lin, Wen;Shen, Guoxiang;Yuan, Xiaoling;Jain, Mohit R.;Yu, Siwang;Zhang, Aihua;Chen, J. Don;Kong, Ah-Ng Tony
    • BMB Reports
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    • v.39 no.3
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    • pp.304-310
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    • 2006
  • Transcription factor NF-E2-related factor 2 (Nrf2) regulates the induction of Phase II detoxifying enzymes and antioxidant enzymes in response to many cancer chemopreventive compounds. In this study, we investigated the role of receptor associated coactivator (RAC3) or steroid receptor coactivator-3 (SRC3) and other nuclear co-regulators including CBP/p300 (CREB-binding protein), CARM1 (Coactivator-associated arginine methyltransferase), PRMT1 (Protein arginine methyl-transferase 1), and p/CAF (p300/CBP-associated factor) in the transcriptional activation of a chimeric Gal4-Nrf2-Luciferase system containing the transactivation domain (TAD) of Nrf2 in HepG2 cells. The results indicated that RAC3 up-regulated the transactivation activity of Gal4-Nrf2-(1-370) in a dose-dependent manner. The enhancement of transactivation domain activity of Gal4-Nrf2-(1-370) by RAC3 was dampened in the presence of dominant negative mutants of RAC3. Next we studied the effects of other nuclear co-regulators including CBP/p300, CARM1, PRMT1 and p/CAF, and the results showed that they had different level of positive effects on this transactivation domain activity of Gal4-Nrf2-(1-370). But importantly, synergistic effects of these co-regulators in the presence of RAC3/SRC3 on the transactivation activity of Gal4-Nrf2-(1-370) were observed. In summary, our present study showed for the first time that the 160 RAC3/SRC3 is involved in the functional transactivation of TAD of Nrf2 and that the other nuclear co-regulators such as CBP/p300, CARM1, PRMT1 and p/CAF can also transcriptionally activate this TAD of Nrf2 and that they could further enhance the transactivation activity mediated by RAC3/SRC3.

Anti-proliferative Activity of Ethanol Extracts of Root of Aralia cordata var. continentalis through Proteasomal Degradation of Cyclin D1 in Human Colorectal Cancer Cells (독활 에탄올 추출물의 대장암 세포에서 Cyclin D1 단백질 분해 유도를 통한 세포 생육 억제활성)

  • Park, Su Bin;Park, Gwang Hun;Song, Hun Min;Park, Ji Hye;Shin, Myeong Su;Son, Ho Jun;Um, Yurry;Jeong, Jin Boo
    • Korean Journal of Medicinal Crop Science
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    • v.25 no.5
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    • pp.328-334
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    • 2017
  • Background: In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of the root of Aralia cordata var. continentalis (Kitagawa) Y. C. Chu (RAc-E70) against human colorectal cancer cells. Methods and Results: RAc-E70 suppressed the proliferation of the human colorectal cancer cell lines, HCT116 and SW480. Although RAc-E70 reduction cyclin D1 expression at the protein and mRNA levels, RAc-E70-induced reduction in cyclin D1 protein level occurred more dramatically than that of cyclin D1 mRNA. The RAc-E70-induced downregulation of cyclin D1 expression was attenuated in the presence of MG132. Additionally, RAc-E70 reduced HA-cyclin D1 levels in HCT116 cells transfected with HA-tagged wild type-cyclin D1 expression vector. RAc-E70-mediated cyclin D1 degradation was blocked in the presence of LiCl, a $GSK3{\beta}$ inhibitorbut, but not PD98059, an ERK1/2 inhibitor and SB203580, a p38 inhibitor. Furthermore, RAc-E70 phosphorylated cyclin D1 at threonine-286 (T286), and LiCl-induced $GSK3{\beta}$ inhibition reduced the RAc-E70-mediated phosphorylation of cyclin D1 at T286. Conclusions: Our results suggested that RAc-E70 may downregulate cyclin D1 expression as a potential anti-cancer target through $GSK3{\beta}$-dependent cyclin D1 degradation. Based on these findings, RAc-E70 maybe a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

Strength criterion of plain recycled aggregate concrete under biaxial compression

  • He, Zhen-Jun;Liu, Gan-Wen;Cao, Wan-Lin;Zhou, Chang-Yang;Jia-Xing, Zhang
    • Computers and Concrete
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    • v.16 no.2
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    • pp.209-222
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    • 2015
  • This paper presents results of biaxial compressive tests and strength criterion on two replacement percentages of recycled coarse aggregate (RPRCA) by mass for plain structural recycled aggregate concrete (RAC) at all kinds of stress ratios. The failure mode characteristic of specimens and the direction of the cracks were observed and described. The two principally static strengths in the corresponding stress state were measured. The influence of the stress ratios on the biaxial strengths of RAC was also analyzed. The experimental results showed that the ratios of the biaxial compressive strength ${\sigma}_{3f}$ to the corresponding uniaxial compressive strength $f_c$ for the two RAC are higher than that of the conventional concrete (CC), and dependent on the replacement percentages of recycled coarse aggregate, stress states and stress ratios; however, the differences of tensile-compressive ratios for the two RAC and CC are smaller. On this basis, a new failure criterion with the stress ratios is proposed for plain RAC under biaxial compressive stress states. It provides the experimental and theoretical foundations for strength analysis of RAC structures subject to complex loads.