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811.
HJ Choi TD Yoon I Muhammad MH Jeong J Lee SY Baek BS Kim S Yoon 《Biochemical and biophysical research communications》2012,419(2):250-255
S100A7 (psoriasin) is a calcium-binding protein that is upregulated in many types of cancer and often associated with poor prognosis. Its role in carcinogenesis has been associated with the stimulation of VEGF and EGF activity. The recent research showed that psoriasin directly interacts with αvβ6 integrin, a protein related to the invasive phenotype of cancer. Moreover, this interaction promotes the αvβ6-dependent invasive activity. The important function of S100A7 in carcinoma development determines a great need for valuable tools enabling its detection, quantification and also activity inhibition. Here, we show the selection of S100A7 specific antibody fragments from the human scFv phage library ETH-2 Gold. We have selected antibody fragments specific for psoriasin, purified them and analyzed by BIAcore affinity measurements. The best clone was subjected to affinity maturation procedure yielding molecule with a subnanomolar affinity towards human S100A7 protein. Selected clone was expressed in a bivalent format and applied for immunostaining analysis, which confirmed the ability of the antigen recognition in physiological conditions. We therefore propose that obtained antibody, that is the first phage display-derived human antibody against psoriasin, can serve as a useful psoriasin binding platform in research, diagnostics and therapy of cancer. 相似文献
812.
Yoon‐Jeong Kim Tae Kwan Park Chaeyoung Kim Heesun Choi In Hee Mook‐Jung Edward H. Koo Sun Ah Park 《Journal of neurochemistry》2012,123(5):856-865
Caspase cleavage of amyloid precursor protein (APP) has been reported to be important in amyloid beta protein (Aβ)‐mediated neurotoxicity. However, the underlying mechanisms are not clearly understood. In this study, we explored the effect of caspase cleavage of APP on tau phosphorylation in relation to Aβ. We found that Asp664 cleavage of APP increased tau phosphorylation at Thr212 and Ser262 in N2A cells and primary cultured hippocampal neurons. Compared with wild‐type APP, protein phosphatase 2A (PP2A) activity was significantly increased when Asp664 cleavage was blocked by the D664A point mutation. Furthermore, we found that over‐expression of C31 reduced PP2A activity. C31 binds directly to the PP2A catalytic subunit, through the asparagine, proline, threonine, tyrosine (NPTY) motif, which is essential for C31‐induced tau hyperphosphorylation. However, it appears that the other fragment produced by Asp664 cleavage, Jcasp, modulates neither PP2A activity nor tau hyperphosphorylation. Asp664 cleavage and accompanying tau hyperphosphorylation were remarkably diminished by blockage of Aβ production using a γ‐secretase inhibitor. Taken together, our results suggest that Asp664 cleavage of APP leads to tau hyperphosphorylation at specific epitopes by modulating PP2A activity as a downstream of Aβ. Direct binding of C31 to PP2A through the C31‐NPTY domain was identified as a mechanism underlying this effect. 相似文献
813.
814.
Kwon MC Choi WY Seo YC Kim JS Yoon CS Lim HW Kim HS Ahn Jh Lee HY 《Journal of biotechnology》2012,157(1):100-106
Aqueous extracts of Centella asiatica L. Urban were encapsulated by an edible biopolymer, gelatin, which has no effect on their cosmetic activities. The nanoparticles were w/o-type spherical liposomes that had an average diameter of 115.0nm. The encapsulation efficiency was estimated to be approximately 67%, which was relatively high for these aqueous extracts. The nanoparticles showed lower cytotoxicity (10%) in human skin fibroblast cells than the unencapsulated crude extract (15%) at 1.0mg/ml, this was possibly because a smaller amount of the extract was present in the nanoparticles. The nanoparticles efficiently reduced the expression of matrix metalloproteinase (MMP)-1 in UV-irradiated cells from 136.1% to 77.6% (UV-irradiated control) and inhibited hyaluronidase expression (>60%) at a concentration of 0.5mg/ml, which was higher than the levels produced by the unencapsulated crude extracts. The nanoparticles had a very high flux through mouse skin and also remained at relatively large concentrations in the derma when compared to the unencapsulated crude extracts. These results clearly indicate that the skin-protective activities of C. asiatica were significantly improved through the nano-encapsulation process. These findings also imply that a crude extract can be used and have the same efficacy as purified compounds, which should reduce the purification process and production costs. 相似文献
815.
Hong YK Lee S Park SH Lee JH Han SY Kim ST Kim YK Jeon S Koo BS Cho KS 《Biochemical and biophysical research communications》2012,419(1):49-53
Amyloid-β-42 (Aβ42) has been implicated in the pathogenesis of Alzheimer's disease (AD). Neuronal Aβ42 expression induces apoptosis and decreases survival and locomotive activity in Drosophila. However, the mechanism by which Aβ42 induces these neuronal impairments is unclear. In this study, we investigated the underlying pathway in theses impairments. JNK activity was increased in Aβ42-expressing brains, and the Aβ42-induced defects were rescued by reducing JNK or caspase activity through genetic modification or pharmacological treatment. In addition, these impairments were restored by Drosophila forkhead box subgroup O (dFOXO) deficiency. These results suggest that the JNK/dFOXO pathway confers a therapeutic potential for AD. 相似文献
816.
The ability to estimate binding affinities of ligands precisely is of paramount importance in designing drugs. Docking programs are used primarily to predict the binding mode of ligands to receptors. However, current scoring functions as used in docking programs are not reliable enough to predict binding affinities of ligands without any further calculations. In the present study, we investigate the usefulness of adding π-π interaction energies between ring groups of residues and ligands to the scoring function for docking. It is found that such addition helps ranking ligand activities more correctly. LMP2 calculation is used to measure π-π interaction energies between ring groups. The result of this simple addition shows possibility of π-π interaction generalization in scoring functions. 相似文献
817.
Universal phenotyping techniques that can discriminate among various states of biological systems have great potential. We applied 557 fluorescent library compounds to NCI's 60 human cancer cell-lines (NCI-60) to generate a systematic fluorescence phenotypic profiling data. By the kinetic fluorescence intensity analysis, we successfully discriminated the organ origin of all the 60 cell-lines. 相似文献
818.
Lee SH Yoon J Shin SH Zahoor M Kim HJ Park PJ Park WS Min do S Kim HY Choi KY 《PloS one》2012,7(4):e34152
BACKGROUND: Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA), a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo. METHODOLOGY/ PRINCIPAL FINDINGS: Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP). VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX), a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl(2) also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice. CONCLUSIONS/ SIGNIFICANCE: Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth. 相似文献
819.
El-Shamy A Shoji I Kim SR Ide Y Imoto S Deng L Yoon S Fujisawa T Tani S Yano Y Seo Y Azuma T Hotta H 《PloS one》2012,7(2):e30513
Pegylated-interferon plus ribavirin (PEG-IFN/RBV) therapy is a current standard treatment for chronic hepatitis C. We previously reported that the viral sequence heterogeneity of part of NS5A, referred to as the IFN/RBV resistance-determining region (IRRDR), and a mutation at position 70 of the core protein of hepatitis C virus genotype 1b (HCV-1b) are significantly correlated with the outcome of PEG-IFN/RBV treatment. Here, we aimed to investigate the impact of viral genetic variations within the NS5A and core regions of other genotypes, HCV-2a and HCV-2b, on PEG-IFN/RBV treatment outcome. Pretreatment sequences of NS5A and core regions were analyzed in 112 patients infected with HCV-2a or HCV-2b, who were treated with PEG-IFN/RBV for 24 weeks and followed up for another 24 weeks. The results demonstrated that HCV-2a isolates with 4 or more mutations in IRRDR (IRRDR[2a]≥4) was significantly associated with rapid virological response at week 4 (RVR) and sustained virological response (SVR). Also, another region of NS5A that corresponds to part of the IFN sensitivity-determining region (ISDR) plus its carboxy-flanking region, which we referred to as ISDR/+C[2a], was significantly associated with SVR in patients infected with HCV-2a. Multivariate analysis revealed that IRRDR[2a]≥4 was the only independent predictive factor for SVR. As for HCV-2b infection, an N-terminal half of IRRDR having two or more mutations (IRRDR[2b]/N≥2) was significantly associated with RVR, but not with SVR. No significant correlation was observed between core protein polymorphism and PEG-IFN/RBV treatment outcome in HCV-2a or HCV-2b infection. CONCLUSION: The present results suggest that sequence heterogeneity of NS5A of HCV-2a (IRRDR[2a]≥4 and ISDR/+C[2a]), and that of HCV-2b (IRRDR[2b]/N≥2) to a lesser extent, is involved in determining the viral sensitivity to PEG-IFN/RBV therapy. 相似文献
820.
Yoon D Ban HJ Kim YJ Kim EJ Kim HC Han BG Park JW Hong SJ Cho SH Park K Lee JS 《BMB reports》2012,45(5):305-310
Allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis are heterogeneous diseases characterized by multiple symptoms and phenotypes. Recent advancements in genetic study enabled us to identify disease associated genetic factors. Numerous genome-wide association studies (GWAS) have revealed multiple associated loci for allergic diseases. However, the majority of previous studies have been conducted in populations of European ancestry. Moreover, the associations of single nucleotide polymorphisms (SNPs) with allergic diseases have not been studied amongst the large-scale general Korean population. Herein, we performed the replication study to validate the previous variants, known to be associated with allergic diseases, in the Korean population. In this study, we categorized three allergic related phenotypes, one allergy and two asthma related phenotypes, based on self-reports of physician diagnosis and their symptoms from 8,842 samples. As a result, we found nominally significant associations of 6 SNPs with at least one allergic related phenotype in the Korean population. 相似文献