Induction of Cell Death in Human Macrophages by a Highly Virulent Korean Isolate of <i>Mycobacterium tuberculosis</i> and the Virulent Strain H37Rv

Sohn, H.,Lee, K.-S.,Kim, S.-Y.,Shin, D.-M.,Shin, S.-J.,Jo, E.-K.,Park, J.-K.,Kim, H.-J. Blackwell Publishing Ltd 2009 Scandinavian journal of immunology Vol.69 No.1

<P>Abstract</P><P>Recent studies have suggested that virulent strains of <I>Mycobacterium tuberculosis</I> induce apoptosis in macrophages less often than do attenuated strains. K-strain, which belongs to the Beijing family, is the most frequently isolated clinical strain of <I>M. tuberculosis</I> in Korea. In this study, we investigated the differential induction of cell death in human monocytic THP-1 cells by K-strain and H37Rv, a virulent but laboratory-adapted strain of <I>M. tuberculosis</I>. Although no significant difference in growth rate was observed between the cells exposed to K-strain and those exposed to H37Rv, the levels of protective cytokines such as tumour necrosis factor (TNF)-&agr;, interleukin (IL)-6 and IL-12p40 were lower in K-strain-infected cells than in H37Rv-infected cells. Cell viability assays showed that both K-strain and H37Rv, but not heat- or streptomycin-killed bacteria, induced THP-1 cell death in a TNF-independent manner. In contrast, double staining with fluorochrome-labelled inhibitors of caspase and propidium iodide and lactate dehydrogenase release assays revealed that K-strain induced significantly higher levels of necrotic cell death, rather than apoptosis, in THP-1 cells than did H37Rv. Anti-apoptotic <I>Bcl-2</I>, <I>Mcl-1</I>, <I>Bfl-1</I> and <I>Bcl-xL</I> in the cells were significantly upregulated following infection with K-strain compared with H37Rv, whereas <I>Bax</I> was slightly upregulated in response to infection with both H37Rv and K-strain. These results suggest that the highly virulent K-strain keeps cellular apoptosis as a host defense mechanism to a minimum and induces necrosis in macrophages.</P>

Novel effects of FTY720 on perinuclear reorganization of keratin network induced by sphingosylphosphorylcholine: Involvement of protein phosphatase 2A and G-protein-coupled receptor-12

Park, M.K.,Park, S.,Kim, H.J.,Kim, E.J.,Kim, S.Y.,Kang, G.J.,Byun, H.J.,Kim, S.H.,Lee, H.,Lee, C.H. North-Holland ; Elsevier Science Ltd 2016 european journal of pharmacology Vol.775 No.-

<P>Sphingosylphosphorylcholine (SPC) evokes perinuclear reorganization of keratin 8 (K8) filaments and regulates the viscoelasticity of metastatic cancer cells leading to enhanced migration. Few studies have addressed the compounds modulating the viscoelasticity of metastatic cancer cells. We studied the effects of sphingosine (SPH), sphingosine 1-phosphate (S1P), FTY720 and FTY720-phosphate (FTY720P) on SPC-induced K8 phosphorylation and reorganization using Western blot and confocal microscopy, and also evaluated the elasticity of PANC-1 cells by atomic force microscopy. FTY720, FTY720P, SPH, and SIP concentration-dependently inhibited SPC-evoked phosphorylation and reorganization of K8, and migration of PANC-1 cells. SPC triggered reduction and narrow distribution of elastic constant K and conversely, FTY720 blocked them. A common upstream regulator of JNK and ERK, protein phosphatase 2A (PP2A) expression was reduced by SPC, but was restored by FTY720 and FTY72P. Butyryl forskolin, a PP2A activator, suppressed SPC-induced K8 phosphorylation and okadaic acid, a PP2A inhibitor, induced K8 phosphorylation. Gene silencing of PP2A also led to K8 phosphorylation, reorganization and migration. We also investigated the involvement of GPR12, a high-affinity SPC receptor, in SPC-evoked keratin phosphorylation and reorganization. GPR12 siRNA suppressed the SPC-triggered phosphorylation and reorganization of K8. GPR12 overexpression stimulated keratin phosphorylation and reorganization even without SPC. FTY720 and FTY720P suppressed the GPR12-induced phosphorylation and reorganization of K8. The collective data indicates that FTY720 and FTY720P suppress SPC-induced phosphorylation and reorganization of K8 in PANC-1 cells by restoring the expression of PP2A via GPR12. These findings might be helpful in the development of compounds that modulate the viscoelasticity of metastatic cancer cells and various SPC actions. (C) 2016 Elsevier B.V. All rights reserved.</P>

Proposed mechanism in the change of cellular composition in the outer medullary collecting duct during potassium homeostasis.

Park, E-Y,Kim, W-Y,Kim, Y-M,Lee, J-H,Han, K-H,Weiner, I D,Kim, J Gutenberg 2012 HISTOLOGY AND HISTOPATHOLOGY Vol.27 No.12

<P>Potassium depletion (K?-D) induces hypertrophy and hyperplasia of collecting duct cells, and potassium repletion (K?-R) induces regression of these changes. The purpose of this study was to examine the time courses of the changes in cellular composition, the origin of intercalated cells (ICs) and the mechanism responsible for these changes. SD rats received K?-depleted diets for 1, 7, or 14 days. After K?-D for 14 days some of the rats received normal diets for 1, 3, 5, or 7 days. In the inner stripe of the outer medulla, K?-D increased significantly the number and proportion of H?-ATPase-positive ICs, but decreased the proportion of H?-ATPase-negative principal cells (PCs). However, proliferation was limited to H?-ATPase-negative PCs. During K?-R, the cellular composition was recovered to control level. Apoptosis increased during K?-R and exclusively limited in H?-ATPase-negative PCs. Double immunolabeling with antibodies to PC and IC markers identified both cells negative or positive for all markers during both K?-D and K?-R. Electron microscopic observation showed that ultrastructure of AE1-positive some cells were similar to AE1-negative some cells during K?-R. LC3 protein expression increased significantly and autophagic vacuoles appeared particularly in PCs on days 14 of K?-D and in ICs on days 3 of K?-R. These results suggest that PCs and ICs may interconvert in response to changes in dietary K+ availability and that autophagic pathways may be involved in the interconversion.</P>

Neural stem cells injured by oxidative stress can be rejuvenated by GV1001, a novel peptide, through scavenging free radicals and enhancing survival signals

Park, H.H.,Yu, H.J.,Kim, S.,Kim, G.,Choi, N.Y.,Lee, E.H.,Lee, Y.J.,Yoon, M.Y.,Lee, K.Y.,Koh, S.H. Elsevier BV 2016 NeuroToxicology Vol.55 No.-

<P>Oxidative stress is a well-known pathogenic mechanism of a diverse array of neurological diseases, and thus, numerous studies have attempted to identify antioxidants that prevent neuronal cell death. GV1001 is a 16-amino-acid peptide derived from human telomerase reverse transcriptase (hTERT). Considering that hTERT has a strong antioxidant effect, whether GV1001 also has an antioxidant effect is a question of interest. In the present study, we aimed to investigate the effects of GV1001 against oxidative stress in neural stem cells (NSCs). Primary culture NSCs were treated with different concentrations of GV1001 and/or hydrogen peroxide (H2O2) for various time durations. The H2O2 decreased the viability of the NSCs in a concentration-dependent manner, with 200 mu M H2O2 significantly decreasing both proliferation and migration. However, treatment with GV1001 rescued the viability, proliferation and migration of H2O2 injured NSCs. Consistently, free radical levels were increased in rat NSCs treated with H2O2, while co-treatment with GV1001 significantly reduced these levels, especially the intracellular levels. In addition, GV1001 restored the expression of survival-related proteins and reduced the expression of death associated ones in NSCs treated with H2O2. In conclusion, GV1001 has antioxidant and neuroprotective effects in NSCs following treatment with H2O2, which appear to be mediated by scavenging free radicals, increasing survival signals and decreasing death signals. (C) 2016 Elsevier B.V. All rights reserved.</P>

Relationship between Stress Gene Polymorphisms and Litter Size by AI in Pigs

Jin, H.J.,Kim, I.C.,Wee, M.S.,Yeon, S.H.,Kim, C.D.,Lee, S.S.,Cho, C.Y.,Cho, S.R.,Son, D.S.,Park, C.K. 韓國受精卵移植學會 2007 한국동물생명공학회지 Vol.22 No.4

This study was performed to investigate the relationship between PSS-HSP70 gene polymorphism and artificial insemination (AI) reproductivity in the pigs. The RFLP polymorphism of PSS and the SSCP polymorphisms of HSP70 K1, K3 and K4 PCR product were detected different patterns. In the experiment for AI of fresh semen, spring and fall season showed higher litter size born of 10.89 head than 10.47 head of summer season. Landrace was showed higher litter size of 9.96 head than that of Duroc and Yorkshire (p<0.05). Stress relating PSS and HSP70 polymorphism of PSS-Normal, HSP70 K1-BB, K3-AB, K4-AA showd a highest litter size born of 10.97 head and litter size born alive of 10.69 head than that of the other polymorphisms(p<0.05). In the experiment for AI of frozen semen, effects of season and pig breeds were not showed for litter size born. The stress relating polymorphism of PSS-Carrier, HSP70 K1-BB, K3-BB, K4-AB showed highest litter size born of 11.29 head and litter size born alive of 10.82 head and PSS-Normal, HSP70 K1-BB, K3-AB, K4-AA showed the lowest litter size born of 8.48 head and litter size born alive of 7.33 head than that of the other polymorphisms(p<0.05). These results suggest that AI litter size born for the stress of forzen thawed semen may be affected by PSS and HSP70 polymorphism in pigs.

Enrichment of Vitamins $D_3$, K and Iron in Eggs of Laying Hens

Park, S.W.,Namkung, H.,Ahn, H.J.,Paik, I.K. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.2

An experiment was conducted to produce eggs enriched with vitamins $D_3$, K and iron in eggs. Six hundred 97-wk-old ISA Brown force molted hens were allocated to completely randomized block arrangement of six dietary treatments: T1; control (C), T2; C+4,000 IU vitamin $D_3$+2.5 mg vitamin K+100 ppm Fe, T3; C+8,000 IU vitamin $D_3$+5.0 mg vitamin K+100 ppm Fe, T4; C+12,000 IU vitamin $D_3$+7.5 mg vitamin K+100 ppm Fe, T5; C+16,000 IU vitamin $D_3$+10.0 mg vitamin K+100 ppm Fe, T6; C+20,000 IU vitamin $D_3$+12.5 mg vitamin K+100 ppm Fe. Fe was supplemented with Fe-methionine. Each treatment consisted of five replicates of ten cages with two birds per cage. Egg production and egg weight were highest in T2 and incidence of soft and broken egg was highest in T6. Haugh unit was not different among treatments although it tended to be increased as dietary vitamins $D_3$ and K increased. Eggshell strength was not different among treatment. Concentrations of vitamin $D_3$ and K in egg yolk increased and plateaued approximately 20 days after feeding supplemented diets. The level of these vitamins peaked at 12,000 IU/kg vitamin $D_3$ and 7.5 mg/kg vitamin K supplementation and then decreased at the higher than these supplementation levels. The peak concentrations of vitamin $D_3$ and vitamin K were 4.6 times and 4.8 times greater than the control, respectively. Supplementary Fe also increased Fe content in egg yolk. It is concluded that vitamin $D_3$ and K in eggs can be effectively enriched by proper supplementation time and level of these vitamins.

Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection

Park, J.K.,Lee, D.H.,Cho, C.H.,Yuk, S.S.,To, E.O.,Kwon, J.H.,Noh, J.Y.,Kim, B.Y.,Choi, S.W.,Shim, B.S.,Song, M.K.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Scientific Pub. Co 2014 Veterinary microbiology Vol.169 No.3

Avian influenza virus (AIV) subtype H9N2 has been evolving rapidly and vaccine escape variants have been reported to cause circulation of infections and economic losses. In the present study, we developed and evaluated ectodomain of the AIV matrix 2 (M2e) protein as a supplementing antigen for oil-based inactivated H9N2 vaccine to increase resistance against vaccine escape variants. AIV H9N2 M2e antigen was expressed in Escherichia coli and supplemented to inactivated H9N2 oil emulsion vaccine. Specific pathogen-free chickens received a single injection of inactivated H9N2 oil emulsion vaccines with or without M2e supplementation. At three weeks post vaccination, hemagglutination inhibition tests and enzyme-linked immunosorbent assays were performed to determine serological immune responses. Challenge study using a vaccine escape H9N2 variant was performed to evaluate the efficacy of M2e supplementation. M2e antigen supplemented in oil emulsion vaccine was highly immunogenic, and a single M2e-supplemented vaccination reduced challenge virus replication and shedding more effectively than non-supplemented vaccination.

Overview of KSTAR research progress and future plans toward ITER and K-DEMO

Park, H.K.,Choi, M.J.,Hong, S.H.,In, Y.,Jeon, Y.M.,Ko, J.S.,Ko, W.H.,Kwak, J.G.,Kwon, J.M.,Lee, J.,Lee, J.H.,Lee, W.,Nam, Y.B.,Oh, Y.K.,Park, B.H.,Park, J.K.,Park, Y.S.,Wang, S.J.,Yoo, M.,Yoon, S.W.,B IOP 2019 Nuclear fusion Vol.59 No.11

<P>A decade-long operation of the Korean Superconducting Tokamak Advanced Research (KSTAR) has contributed significantly to the operation of superconducting tokamak devices and the advancement of tokamak physics which will be beneficial for the ITER and K-DEMO programs. Even with limited heating capability, various conventional as well as new operating regimes have been explored and have achieved improved performance. As examples, a long pulse high-confinement mode operation with and without an edge-localized mode (ELM) crash was well over 70 and 30 s, respectively. The unique capabilities of KSTAR allowed it to improve the capability of controlling harmful instabilities, and they have been instrumental in uncovering much new physics. The highlights are that the L/H transition threshold power is sensitive to the resonant magnetic perturbation (RMP) and insensitive to non-resonant magnetic perturbation. Co-<I>I</I> <SUB>p</SUB> offset rotation dominated by an electron channel predicted by general neoclassical toroidal viscosity theory was confirmed. Improved heat dispersal in a divertor system using three rows of rotating RMP was demonstrated and predictive control of the ELM-crash with <I>a priori</I> modeling was successfully tested. In magnetohydrodynamic physics, validation of the full reconnection model (i.e. <I>q</I> <SUB>0</SUB>  >  1 right after the sawtooth crash) and self-consistent validation of the anisotropic distribution of turbulence amplitude and flow in the presence of the 2/1 island with theoretical models were achieved. The turbulence amplitude induced by RMP was linearly increased with the slow RMP coil current ramp-up time (i.e. the magnetic diffusion time scale). The <I>D</I> <SUB> <I>α</I> </SUB> spikes (i.e. ELM-crash amplitude) was linearly decreased with the turbulence amplitude and not correlated with the perpendicular electron flow. In the turbulence area, a non-diffusive ‘avalanche’ transport event and the role of a quiescent coherent mode in confinement were studied. To accommodate the anticipation of a higher performance of the KSTAR plasmas with the increased heating powers, a new divertor/internal interface with a full active cooling system will be implemented after a full test of the new heating (neutral beam injection II and electron cyclotron heating) and current drive (CD) (Helicon and lower hybrid CD) systems. An upgrade plan for the internal hardware, heating systems and efficient CD system may allow for a long pulse operation of higher performance plasmas at <I>β</I> <SUB>N</SUB>  >  3.0 with <I>f</I> <SUB>bs</SUB> ~ 0.5 and <I>T</I> <SUB>i</SUB>  >  10 keV.</P>

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>

Advanced H2O2 oxidation for diethyl phthalate degradation in treated effluents: effect of nitrate on oxidation and a pilot-scale AOP operation

Ko, K. B.,Park, C. G.,Moon, T. H.,Ahn, Y. H.,Lee, J. K.,Ahn, K. H.,Park, J. H.,Yeom, I. T. IWA Publishing 2008 Water Science & Technology Vol.58 No.5

<P>One of the objectives of this study was to delineate the effect of nitrate on diethyl phthalate (DEP) oxidation by conducting a bench-scale ultraviolet (UV)/H2O2 and O3/H2O2 operations as suggested in a previous study. We also aim to investigate DEP oxidation at various UV doses and H2O2 concentrations by performing a pilot-scale advanced oxidation processes (AOP) system, into which a portion of the effluent from a pilot-scale membrane bioreactor (MBR) plant was pumped. In the bench-scale AOP operation, the O3 oxidation alone as well as the UV irradiation without H2O2 addition could be among the desirable alternatives for the efficient removal of DEP dissolved in aqueous solutions at a low DEP concentration range of 85±15 μg/L. The adverse effect in the UV/H2O2 process was significantly greater than that in the UV oxidation alone, and its oxidation was almost halved by the nitrate. However, the nitrate clearly enhanced the DEP oxidation in the O3 oxidation and O3/H2O2 process. Especially, the addition of nitrate almost doubled the DEP oxidation efficiency in the O3/H2O2 process. The series of pilot-scale AOP operations confirmed that about 30-50% of DEP dissolved in the treated MBR effluent streams was, at least, oxidized by the O3 oxidation alone as well as the UV irradiation without H2O2 addition. The UV photolysis of H2O2 was most effective for DEP degradation with an H2O2 concentration of 40 mg/L at a UV dose of 500 mJ/cm2.</P>