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Jong-Gil Park,
Ji-Young Yoo,
Se-Jin Jeong,
Jae-Hoon Choi,
Mi-Ran Lee,
Mi-Ni Lee,
Jeong Hwa Lee,
Hyoung Chin Kim,
Hanjoong Jo,
Dae-Yeul Yu,
Sang Won Kang,
Sue Goo Rhee, Mun-Han Lee,
Goo Taeg Oh
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ABSTRACT: Peroxiredoxin 2 (Prdx2), a thiol-specific peroxidase, has been reported to regulate proinflammatory responses, vascular remodeling, and global oxidative stress.
Although Prdx2 has been proposed to retard atherosclerosis development, no direct evidence and mechanisms have been reported.
We show that Prdx2 is highly expressed in endothelial and immune cells in atherosclerotic lesions and blocked the increase of endogenous H(2)O(2) by atherogenic stimulation. Deficiency of Prdx2 in apolipoprotein E-deficient (ApoE(-/-)) mice accelerated plaque formation with enhanced activation of p65, c-Jun, JNKs, and p38 mitogen-activated protein kinase; and these proatherogenic effects of Prdx2 deficiency were rescued by administration of the antioxidant ebselen. In bone marrow transplantation experiments, we found that Prdx2 has a major role in inhibiting atherogenic responses in both vascular and immune cells. Prdx2 deficiency resulted in increased expression of vascular adhesion molecule-1, intercellular adhesion molecule-1, and monocyte chemotactic protein-1, which led to increased immune cell adhesion and infiltration into the aortic intima. Compared with deficiency of glutathione peroxidase 1 or catalase, Prdx2 deficiency showed a severe predisposition to develop atherosclerosis.
Prdx2 is a specific peroxidase that inhibits atherogenic responses in vascular and inflammatory cells, and specific activation of Prdx2 may be an effective means of antiatherogenic therapy.
Circulation Research 08/2011; 109(7):739-49. · 9.49 Impact Factor
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Jae-Hoon Choi,
Jong-Gil Park,
Hyung Jun Jeon,
Mi-Sun Kim,
Mi-Ran Lee,
Mi-Ni Lee,
SeongKeun Sonn,
Jae-Hong Kim, Mun Han Lee,
Myung-Sook Choi,
Yong Bok Park,
Oh-Seung Kwon,
Tae-Sook Jeong,
Woo Song Lee,
Hyun Bo Shim,
Dong Hae Shin,
Goo Taeg Oh
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ABSTRACT: A variety of benzylidenethiazole analogs have been demonstrated to inhibit 5-lipoxygenase (5-LOX). Here we report the anti-atherogenic potential of 5-(4-hydroxy- 2,3,5-trimethylbenzylidene) thiazolidin-2,4-dione (HMB-TZD), a benzylidenethiazole analog, and its potential mechanism of action in LDL receptor-deficient (Ldlr-/-) mice. HMB-TZD Treatment reduced leukotriene B4 (LTB4) production significantly in RAW264.7 macrophages and SVEC4-10 endothelial cells. Macrophages or endothelial cells pre-incubated with HMB-TZD for 2 h and then stimulated with lipopolysaccharide or tumor necrosis factor-alpha (TNF-α) displayed reduced cytokine production. Also, HMB-TZD reduced cell migration and adhesion in accordance with decreased proinflammatory molecule production in vitro and ex vivo. HMB-TZD treatment of 8-week-old male Ldlr-/- mice resulted in significantly reduced atherosclerotic lesions without a change to plasma lipid profiles. Moreover, aortic expression of pro-atherogenic molecules involved in the recruitment of monocytes to the aortic wall, including TNF-α , MCP-1, and VCAM-1, was downregulated. HMB-TZD also reduced macrophage infiltration into atherosclerotic lesions. In conclusion, HMB-TZD ameliorates atherosclerotic lesion formation possibly by reducing the expression of proinflammatory molecules and monocyte/macrophage recruitment to the lesion. These results suggest that HMB-TZD, and benzylidenethiazole analogs in general, may have therapeutic potential as treatments for atherosclerosis.
Experimental and Molecular Medicine 06/2011; 43(8):471-8. · 2.48 Impact Factor
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Jae-Hoon Choi,
Hyung Jun Jeon,
Jong-Gil Park,
Seong Keun Sonn,
Mi-Ran Lee,
Mi-Ni Lee,
Hye Jin You,
Geun-Young Kim,
Jae-Hong Kim, Mun Han Lee,
Oh-Seung Kwon,
Ki-Hoan Nam,
Hyoung-Chin Kim,
Tae-Sook Jeong,
Woo Song Lee,
Goo Taeg Oh
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ABSTRACT: Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX), which play pivotal roles in atherogenesis, have been reported to be involved in plaque stability. Licofelone, a dual COX and 5-LOX inhibitor, has been reported to possess anti-atherogenic effect in rabbit atherosclerosis model. We therefore investigated the anti-atherogenic effect of BHB-TZD [5-(3,5-di-tert-butyl-4-hydroxybenzylidene)thiazolidin-2,4-dione], a dual COX and 5-LOX inhibitor, in low density lipoprotein receptor null (LDLR-/-) mice. Fifteen LDLR-/- mice were fed a western diet (control group), whereas 15 were fed a western diet plus 0.1% (w/w) BHB-TZD (BHB-TZD group). After 8 weeks, the BHB-TZD group had markedly lower serum levels of leukotriene B(4) and prostaglandin E(2) than the control group. Interestingly, BHB-TZD treatment also reduced plasma triglyceride level without significant changes in total cholesterol and HDL levels. Compared with control mice, BHB-TZD fed mice had 52% fewer fatty streak lesions in the aortic sinus, as well as fewer initial lesions in the aortic arch. Macrophage infiltration into the lesions was 40% lower, and collagen and smooth muscle cells were increased by 102% and 96%, respectively, in the BHB-TZD group compared with the control group. In addition, aortic expression of proatherogenic molecules including TNF-alpha, IL-1beta, IL-6, MCP-1 and VCAM-1, was lower in the BHB-TZD group than the control group. BHB-TZD treatment also reduced MMP-2 and MMP-9 expressions in aorta. In conclusion, BHB-TZD effectively attenuated atherosclerosis in mouse model, suggesting its therapeutic potential for atherosclerosis.
Atherosclerosis 09/2010; 212(1):146-52. · 3.79 Impact Factor
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Byeong-Teck Kang,
Kyung-Seok Kim,
Mi-Sook Min,
Young-Jin Chae,
Jung-Won Kang,
Junghee Yoon,
Jihye Choi,
Je-Kyung Seong,
Han-Chan Park,
Junghwa An, Mun-Han Lee,
Hee-Myung Park,
Hang Lee
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ABSTRACT: To investigate the population structure of five dog breeds in South Korea and to validate polymorphic microsatellite markers for the parentage test, microsatellite loci analyses were conducted for two Korean native dog breeds, Poongsan and Jindo, and three imported dog breeds, German Shepherd, Beagle and Greyhound. Overall genetic diversity was high across all dog breeds (expected heterozygosity range: 0.71 to 0.85), although breeds differed in deviations from Hardy-Weinberg equilibrium (HWE). Significant reduction of heterozygosity in the Poongsan and Greyhound breeds was caused by non-random mating and population substructure within these breeds (the Wahlund effects). The close relationship and high degree of genetic diversity for two Korean native dog breeds were substantial. The mean polymorphism information content value was highest in Jindos (0.82) and Poongsans (0.81), followed by Beagles (0.74), Greyhounds (0.72), and German Shepherds (0.66). Accumulated exclusion power values, as an indication of marker validity for parentage tests, were varied but very high across breeds, 0.9999 for Jindos, Poongsans, and Beagles, 0.9997 for Greyhounds, and 0.9995 for German Shepherds. Taken together, the microsatellite loci investigated in this study can serve as suitable markers for the parentage test and as individual identification to establish a reliable pedigree verification system of dog breeds in South Korea. This study also stresses that the population subdivision within breeds can become an important cause of deviation from HWE in dog breeds.
Genes & Genetic Systems 07/2009; 84(3):245-51. · 0.95 Impact Factor
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ABSTRACT: Gaegurin 4 (GGN4), an antimicrobial peptide isolated from a Korean frog, is five times more potent against Gram-positive than Gram-negative bacteria, but has little hemolytic activity. To understand the mechanism of such cell selectivity, we examined GGN4-induced K(+) efflux from target cells, and membrane conductances in planar lipid bilayers. The K(+) efflux from Gram-positive M. luteus (2.5 microg/ml) was faster and larger than that from Gram-negative E. coli (75 microg/ml), while that from RBC was negligible even at higher concentration (100 microg/ml). GGN4 induced larger conductances in the planar bilayers which were formed with lipids extracted from Gram-positive B. subtilis than in those from E. coli (p<0.01), however, the effects of GGN4 were not selective in the bilayers formed with lipids from E. coli and red blood cells. Addition of an acidic phospholipid, phosphatidylserine to planar bilayers increased the GGN4-induced membrane conductance (p<0.05), but addition of phosphatidylcholine or cholesterol reduced it (p<0.05). Transmission electron microscopy revealed that GGN4 induced pore-like damages in M. luteus and dis-layering damages on the outer wall of E. coli. Taken together, the present results indicate that the selectivity of GGN4 toward Gram-positive over Gram-negative bacteria is due to negative surface charges, and interaction of GGN4 with outer walls. The selectivity toward bacteria over RBC is due to the presence of phosphatidylcholine and cholesterol, and the trans-bilayer lipid asymmetry in RBC. The results suggest that design of selective antimicrobial peptides should be based on the composition and topology of membrane lipids in the target cells.
Korean Journal of Physiology and Pharmacology 02/2009; 13(1):39-47. · 0.96 Impact Factor
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ABSTRACT: Because of the continuous advent of new modes of antimicrobial resistance, it has become difficult to control vancomycin-resistant enterococci (VRE) with standard antibiotics. Therefore, in the interest of public health, early diagnostic methods and a greater knowledge of the pathogenic process are urgently needed to prevent the spread of VRE in humans and animals. To this end, we sought immunogenic proteins suitable for the serological diagnosis of VanA-, VanB-, VanC1-, and VanC2-type VRE. Proteins were extracted from cell envelope (CE) and cytoplasm (CP), and anti-VRE guinea pig serum was used to identify immunogenic proteins. Two immunogenic proteins of 129 and 29 kDa were identified in the CE and CP of VanA, respectively, while a 28-kDa protein was identified in the CP of VanB. Additionally, the CE of VanC1 contained two immunogenic proteins of 30 and 46 kDa, while the CP of VanC1 contained two proteins of 19 and 30 kDa. The CE of VanC2 possessed one immunogenic protein of 40 kDa. These proteins, which were specific to individual subtypes of VRE, will likely prove useful in the serological diagnosis of enterococcal infections and in the study of enterococcal pathogenesis.
Journal of Immunoassay and Immunochemistry 02/2008; 29(4):319-31. · 0.69 Impact Factor
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ABSTRACT: DNA-based analysis was performed using partial mitochondrial cytochrome b genes of five mammalian specimens and Chromo-Helicase-DNA-binding (CHD) genes of five pheasants to determine whether specimens were from illegally hunted animals. Mammalian specimens were identified as being those of horse, roe deer, and cow through gene amplification using cytb981f and cytb981r primer set and sequencing. CHD genes were revealed to be those of three male and two female pheasants through polymerase chain reaction amplification. Because hunting of roe deers and female pheasants is prohibited in Korea, these results provided forensic evidences of illegal wild animal hunting.
Forensic Science International 04/2007; 167(1):59-61. · 2.30 Impact Factor
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ABSTRACT: Monoclonal antibody against kanamycin was prepared, and competitive direct ELISA and immunochromatographic assay were developed using the antibody to detect kanamycin in animal plasma and milk. The monoclonal antibody produced was identified to be IgG1, which has a kappa light chain. No cross-reactivity of the antibody was detected with other aminoglycosides, indicating that the monoclonal antibody was highly specific for kanamycin. Based on competitive direct ELISA, the detection limits of kanamycin were determined to be 1.1 ng/ml in PBS, 1.4 ng/ml in plasma, and 1.0 ng/ml in milk. The concentration of intramuscularly injected kanamycin was successfully monitored in rabbit plasma with competitive direct ELISA. Based on the colloidal gold-based immunochromatographic assay, the detection limits of kanamycin were estimated to be about 6-8 ng/ml in PBS, plasma, and milk. The immunochromatographic assay would be suitable for rapid and simple screening of kanamycin residues in veterinary medicine. Screened positives can be confirmed using a more sensitive laboratory method such as competitive direct ELISA. Therefore, the assays developed in this study could be used to complement each other as well as other laboratory findings. Moreover, instead of slaughtering the animals to obtain test samples, these methods could be applied to determine kanamycin concentration in the plasma of live animals.
Journal of Veterinary Science 07/2006; 7(2):111-7. · 1.16 Impact Factor
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ABSTRACT: Reliable analytical methods are required to monitor neomycin residue levels in the livestock products. In particular, a more simple and rapid detection method is required in the veterinary fields.
Competitive direct ELISA and immunochromatographic assay were developed using monoclonal antibody to detect neomycin in the animal plasma and milk.
No cross-reactivity of the antibody was observed with other aminoglycosides based on competitive direct ELISA methods, indicating that the antibody is highly specific for neomycin. Based on the standard curves, the detection limits were determined to be 6.85 ng/ml in PBS, 3.61 ng/ml in plasma, and 2.73 ng/ml in milk, respectively. Recoveries of neomycin from spiked plasma and milk at levels of 50-200 ng/ml ranged from 87% to 108%. Concentration of intramuscularly injected neomycin was successfully monitored in the rabbit plasma through competitive direct ELISA. Immunochromatographic method was also developed using colloidal gold-conjugated monoclonal antibody. Through this method, the detection limits were estimated to be about 10 ng/ml of neomycin in PBS, plasma, and milk.
Immunochromatographic assay developed in this study is suitable for the simple screening of neomycin residues in the veterinary field. Observed positives can be confirmed using a more sensitive laboratory method such as competitive direct ELISA.
Clinica Chimica Acta 03/2006; 364(1-2):260-6. · 2.54 Impact Factor
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ABSTRACT: Competitive direct enzyme-linked immunosorbent assay (ELISA) and the immunochromatographic assay were developed using a monoclonal antibody to detect gentamicin in the animal plasma and milk. No cross-reactivity of the antibody was observed with other aminoglycosides based on competitive direct ELISA, indicating that the antibody is highly specific for gentamicin. On the basis of the standard curves, the detection limits were determined to be 0.9 ng/mL in phosphate-buffered saline (PBS), 1.0 ng/mL in plasma, and 0.5 ng/mL in milk, respectively. Recoveries of gentamicin from spiked plasma and milk at levels of 25-100 ng/mL ranged from 85 to 112%. The concentration of intramuscularly injected gentamicin was successfully monitored in the rabbit plasma through competitive direct ELISA. The detection limits were estimated to be about 6 ng/mL of gentamicin in PBS, plasma, and milk using the colloidal gold-based immunochromatographic assay, which is suitable for the simple screening of gentamicin residues in the veterinary field. Observed positives can be confirmed using a more sensitive laboratory method such as competitive direct ELISA. Therefore, the assays developed in this study could complement each other as well as veterinary field and laboratory findings.
Journal of Agricultural and Food Chemistry 11/2005; 53(20):7639-43. · 2.82 Impact Factor
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ABSTRACT: The toxicity of acrylamide was evaluated through mutagenicity of Salmonella, chromosome aberration of Chinese hamster lung fibroblasts, micronucleus formation in mice and reproductive toxicity in rats. Based on Ames test, acrylamide showed mutagenic potency for strains TA98 and TA100. Moreover, both chromosomal aberration assay and micronucleus assay indicated that acrylamide might have genotoxic potency; the chromosomal aberration frequencies were observed to be proportional to acrylamide concentrations of 5-50 mM, and acrylamide significantly increased micronuclei in peripheral blood cells of mice at doses of higher than 72.5 mg/kg. Male rats were treated with acrylamide at doses of 0, 5, 15, 30, 45, or 60 mg/kg/day for 5 consecutive days, and the toxicity of acrylamide was observed. In the group treated with the highest dose of acrylamide (60 mg/kg/day), the loss of body weight and reduced testis weight were observed. Also the epididymides weights were reduced significantly in all the groups treated with acrylamide. The number of sperms in cauda epididymidis decreased significantly in an acrylamide dose-dependent manner. Rats treated with 60 mg/kg/day of acrylamide showed several histopathological lesions in the seminiferous tubules. There were thickening and multiple layering of the tubular endothelium, and the formation of many multinucleated giant cells in seminiferous tubules. Taken together, acrylamide not only causes the genotoxicity of eukaryotic cells and mice but also shows the toxicological effects on reproductive system in male rats.
Journal of Veterinary Science 07/2005; 6(2):103-9. · 1.16 Impact Factor
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ABSTRACT: The developmental expression of heat shock protein 108 (HSP108) mRNA was mapped in chicken brain using in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR showed that HSP108 mRNA increased from embryonic day 5 (E5) to 13 (E13), significantly decreased from E17 to E21 and then increased again at the adult stage. In situ hybridization showed that while intense HSP108 positive (HSP108+) signals were localized in the cerebellum from E7 to E14, the intensities of these signals were significantly decreased at E17. However, at the adult stage, HSP108 expression increased in a cell type dependent manner. A decrease in HSP108 mRNA expression during differentiation was also observed in an in vitro study of brain cells treated with nerve growth factor (NGF).
Neuroscience Letters 12/2004; 370(2-3):140-5. · 2.11 Impact Factor
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Mi-Sook Min,
Hideo Okumura,
Dong-Jun Jo,
Jung-Hwa An,
Kyung-Seok Kim,
Chang-Bae Kim,
Nam-Sik Shin, Mun-Han Lee,
Chang-Hoon Han,
Inna V Voloshina,
Hang Lee
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ABSTRACT: To investigate the molecular phylogenetic status of the Korean goral, Nemorhaedus caudatus raddeanus, and Japanese serow, Capricornis crispus, we determined partial sequences of the mitochondrial cytochrome b gene of twelve Korean gorals and sixteen Japanese serows, and compared them with those of the major lineages of Rupicaprini species including two other Nemorhaedus species and two other Capricornis species. The Korean gorals examined possessed two haplotypes with only one nucleotide difference between them, while the Japanese serows showed slightly higher sequence diversity with five haplotypes. Genetic distances and molecular phylogenetic trees indicated that there is considerable genetic divergence between the Korean goral and N. caudatus (the Chinese goral) [Groves and Shields (1996)], but virtually none between Korean and Russian gorals. The Korean and Russian gorals may therefore be distinct from the Chinese goral. The data highlight the importance of conservation of the goral populations of these regions, and the need to reconsider the taxonomic status of Korean and Russian gorals. Our study also clearly demonstrated sufficient genetic distance between serows and gorals to justify their assignment to separate genera. Of the three species of Capricornis, the Formosan serow, C. swinhoei is more closely related to C. sumatraensis than to the Japanese serow, suggesting that the Formosan serow is a distinct species. Preliminary data on intraspecific genetic variation in the Japanese serow are also presented.
Molecules and Cells 05/2004; 17(2):365-72. · 2.18 Impact Factor
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ABSTRACT: Both hydropathy plot and in vitro translation results predict the topology of SR-BI; the receptor is an integral membrane protein of 509 amino acids, consisting of a short cytoplasmic N-terminus of 9 amino acids followed by a first transmembrane domain of 22 amino acids, the extracellular domain of 408 amino acids, the second transmembrane domain of 22 amino acids, and the cytoplasmic C-terminus of 47 amino acids. The immunoblot of rBBMV in the presence or absence of pAb589 peptide antigen (the C-terminal 22 amino acid residues of SR-BI) confirmed that the bands at apparent molecular weight of 140 and 210 kDa are SR-BI related protein which might be multimeric forms of SR-BI. 125I apo A-I overlay analysis showed that SR-BI can bind to its ligand, apo A-I, only when it is thoroughly matured--glycosylated and dimerized. The antibody which was generated against extracellular domain of SR-BI (pAb230) not only prevented 125I-labeled apo A-I from binding to 140 kDa band but also inhibited the esterified cholesterol uptake of rabbit BBMV with its IC50 value of 40 microg/ml of IgG. In contrast, the antibody generated against the C-terminal domain of SR-BI (pAb589) did not show any effect either on cholesterol uptake of rabbit BBMV or 125I-labeled apo A-I binding to 140 kDa band. Overall results show that the ligand binding site of SR-BI in rabbit BBMV is located in extracellular domain, and SR-BI is only functional when it is part of dimeric forms which rationalize the previously found cooperative nature of the binding interaction and maybe a fundamental finding towards the so far poorly understood mechanism of SR-BI function.
Journal of Veterinary Science 01/2003; 3(4):265-72. · 1.16 Impact Factor
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ABSTRACT: A combination of nisin and heat treatment was found to inhibit Escherichia coli O157:H7 effectively. After organisms were heated at 50, 52.5, and 55 degrees C for 5, 10, and 15 min, respectively, nisin was incorporated into the plates of E. coli O157:H7 at 0, 25, 50, and 100 IU/ml. The concentration of 100 IU/ml nisin significantly inhibited the growth of E. coli O157:H7 heated at 50 and 52.5 degrees C for 15 min. Nisin treatment at 100 IU/ml for 6 h resulted in the elimination of E. coli O157:H7 heated at 55 degrees C for 10 and 15 min.
Journal of food protection 03/2002; 65(2):408-10. · 1.94 Impact Factor
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ABSTRACT: Toxicological effects of acrylamide on differential gene expression profile of rat testis were evaluated. Acrylamide induced morphological sperm defects, and decreased sperm concentration in cauda epididymis. Serum testosterone level and Leydig cell viability were also decreased dose-dependently, which resulted in decreased spermatogenesis. Acrylamide-induced histopathological lesions, such as formation of multinucleated giant cells and vacuolation, and numerous apoptotic cells were observed in seminiferous tubules. cDNA microarray analysis revealed that genes related to testicular-functions, apoptosis, cellular redox, cell growth, cell cycle, and nucleic acid-binding were up/down-regulated in testes isolated from acrylamide-treated group (60 mg/kg/day). Acrylamide toxicity appears to increase Leydig cell death and perturb gene expression levels, contributing to sperm defects and various abnormal histopathological lesions including apoptosis in rat testis.
Reproductive Toxicology 19(4):527-34. · 3.23 Impact Factor
