Publications (21)59.43 Total impact
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Article: Targeting cellular apoptotic pathway with peptides from marine organisms.
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ABSTRACT: Apoptosis is a critical defense mechanism against the formation and progression of cancer and exhibits distinct morphological and biochemical traits. Targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents. Peptides from marine organisms have become important sources in the discovery of antitumor drugs, especially when modern technology makes it more and more feasible to collect organisms from seas. This primer summarizes several marine peptides, based on their effects on apoptotic signaling pathways, although most of these peptides have not yet been studied in depth for their mechanisms of action. Novel peptides that induce apoptosis signal pathway are presented in association with their pharmacological properties.Biochimica et Biophysica Acta 03/2013; · 4.66 Impact Factor -
Article: Identification of Streptomyces sp. nov. WH26 producing cytotoxic compounds isolated from marine solar saltern in China.
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ABSTRACT: A moderately halophilic actinomycetes strain, designated as WH26, was isolated from Weihai Solar Saltern in China. The identification of the strain WH26 was performed by its morphological characteristics, physiological and biochemical tests as well as phylogenetic analysis based on 16S rRNA sequence comparison. The results showed that the nucleotide sequence of the 16S rRNA gene (1,677 bp) of the strain WH26 exhibited close similarity (97-99 %) with other Streptomyces 16S rRNA genes and the strain WH26 was identified to belong to the genus Streptomyces. An ethyl acetate extraction of Streptomyces sp. nov. WH26 demonstrated significant cellular toxicity. Two compounds, 8-O-methyltetrangulol and naphthomycin A were isolated from the extract via silica gel column chromatography and HPLC. These two compounds showed potent cytotoxic activity against several human tumor cell lines including A549, HeLa, BEL-7402 and HT-29. The present studies suggest that moderately halophilic actinomycetes may be a novel biological source for the discovery of anticancer agents.MIRCEN Journal of Applied Microbiology and Biotechnology 02/2013; · 1.08 Impact Factor -
Article: Mere15, a novel polypeptide from Meretrix meretrix, inhibits adhesion, migration and invasion of human lung cancer A549 cells via down-regulating MMPs.
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ABSTRACT: Context: Mere15 is a novel antitumor polypeptide purified from Meretrix meretrix Linn. (Veneridae). Previous studies have shown that the polypeptide induced cell death via intrinsic mitochondrial pathway. Objective: In the present study, the effects of Mere15 on cell adhesion, migration, invasion, as well as secretion and expression of matrix metalloproteinases (MMPs) were studied in human lung adenocarcinoma A549 cells. Materials and methods: The effect of Mere15 on cell adhesion, migration and invasion were studied by cell adhesion and transwell assay. The expression of MMPs was determined by gelatin zymography and RT-PCR analysis. Results: The ability of cell adhesion was decreased by 86.74% at the concentration of 12.0 μg/mL of Mere15. And the migration and invasion of A549 cells were decreased with the inhibition ratio of, 69.22 and 53.84% when treated with 15.0 μg/mL of Mere15. Further study also revealed that treatment of the cancer cells with Mere15 (15.0 μg/mL), the secretion of MMP-2 and MMP-9 were down-regulated with the inhibition ratio of 72.00 and 93.24% and the inhibition rate of mRNA expression of MMP-2 and MMP-9 was 57.54 and 91.22%, respectively. Discussion and conclusion: The study demonstrates that Mere15 inhibits tumor growth via both pro-apoptotic and antimetastasis pathways, and the polypeptide has potential to be developed as a multi-target therapeutic agent for the treatment of human lung cancer.Pharmaceutical Biology 11/2012; · 0.88 Impact Factor -
Article: Characterization of the high cytochalasin E and rosellichalasin producing-Aspergillus sp. nov. F1 isolated from marine solar saltern in China.
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ABSTRACT: A moderately halophilic fungus F1 was isolated from a marine solar saltern in Weihai, China. The identification of the fungus F1 was performed by the morphological characteristics, physiological and biochemical tests as well as phylogenetic analysis based on ITS (internal transcribed spacer)-5.8S rDNA region sequence comparison. The strain was identified as belonging to the genus Aspergillus and designated as Aspergillus sp. nov. F1. Furthermore, Aspergillus sp. nov. F1 grew well in 3-15 % (w/v) NaCl, and with increasing of salinity, the generation of secondary metabolites with cytotoxicity was also augmented. Three compounds with cytotoxicity were isolated from the ethyl acetate extract of the whole broth and mycelia of Aspergillus sp. nov. F1, and identified as ergosterol, rosellichalasin and cytochalasin E, respectively. Especially, ergosterol showed high potent cytotoxic activity to human colon cancer cell line RKO with IC(50) of 3.3 ± 0.5 μM. Considering the high cytochalasin production and the simple and economical fermentation of Aspergillus sp. nov. F1, the strain could be used as potential strain for large scale production of the cytochalasin E and rosellichalasin.MIRCEN Journal of Applied Microbiology and Biotechnology 08/2012; · 1.08 Impact Factor -
Article: Oleanolic acid potentiates the antitumor activity of 5-fluorouracil in pancreatic cancer cells.
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ABSTRACT: The antitumor activity of oleanolic (OA) has attracted attention due to its marked antitumor effects and pharmacological safety. In the present study, the effects of the combination of OA and 5-fluorouracil (5-FU) on Panc-28 human pancreatic cells were studied. The results showed that combined use of OA and 5-FU synergistically potentiated cell death effects on Panc-28 cells, and the pro-apoptotic effects were also increased. Further study revealed that the combined treatment could enhance mitochondrial depolarization, lysosomal membrane permeabilization (LMP) and leakage of cathepin D, while the release of cytochrome C did not display significant changes. The expression of apoptosis related proteins was also affected in cells treated with the combination of OA and 5-FU, including activation of caspases-3 and the expression of Bcl-2/Bax, survivin and NF-κB. Our results provide evidence that combination of OA and 5-FU may serve as a novel strategy for the treatment of pancreatic cancer.Oncology Reports 07/2012; 28(4):1339-45. · 1.84 Impact Factor -
Article: Oleanolic acid arrests cell cycle and induces apoptosis via ROS-mediated mitochondrial depolarization and lysosomal membrane permeabilization in human pancreatic cancer cells.
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ABSTRACT: Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits potential anti-tumor activity against many tumor cell lines. This study aims to examine the anti-tumor activity of OA on pancreatic cancer cells and its potential molecular mechanism. The results showed that the proliferation of Panc-28 cells was inhibited by OA in a concentration-dependent manner, with an IC(50) (The half maximal inhibitory concentration) value of 46.35 µg ml(-1) , as determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The cell cycle was arrested in S phase and G2/M phase by OA. The study also showed that OA could induce remarkable apoptosis, evidenced by an increased percentage of early/late apoptotic cells, DNA ladder and nuclear morphology change. Further study revealed that OA could induce Reactive Oxygen Species (ROS) generation, mitochondrial depolarization, release of cytochrome C, lysosomal membrane permeabilization and leakage of cathepin B. The expression of apoptosis-correlated proteins was also affected in cells treated with OA, including activation of caspases-3/9 and cleavage of PARP. Further study confirmed that ROS scavenger vitamin C could reverse the apoptosis induced by OA in Panc-28 cells. Our results provide evidence that OA arrests the cell cycle and induces apoptosis, possibly via ROS-mediated mitochondrial and a lysosomal pathway in Panc-28 cells. Copyright © 2012 John Wiley & Sons, Ltd.Journal of Applied Toxicology 06/2012; · 2.48 Impact Factor -
Article: Zebrafish p53 protein enhances the translation of its own mRNA in response to UV irradiation and CPT treatment.
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ABSTRACT: p53 protein is an important regulatory factor involved in cell growth and development. In our previous study, we demonstrated that recombined zebrafish p53 protein could specifically bind to its own mRNA in vitro. To determine if a similar interaction exists in zebrafish and if this interaction affects zebrafish development, in the present study, we investigated the interaction of p53 protein and its mRNA in zebrafish embryos. Our results revealed that expressed zebrafish p53 protein could bind with its own mRNA in zebrafish embryos. Furthermore, the endogenous activated or ectopically expressed p53 protein could enhance the relative activity of Renilla luciferase fused with p53 3'UTR in response to UV irradiation and CPT treatment, and retarded development of zebrafish embryos was observed.FEBS letters 04/2012; 586(8):1220-5. · 3.54 Impact Factor -
Article: A novel polypeptide from Meretrix meretrix Linnaeus inhibits the growth of human lung adenocarcinoma.
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ABSTRACT: A novel polypeptide (Mere15) was purified from Meretrix meretrix Linnaeus by ammonium sulfate fractionation, ion exchange, gel filtration and reversed phase chromatography. Mere15 exhibited selective cytotoxicity to several human cancer cells. In vivo study showed that Mere15 significantly suppressed the growth of human lung adenocarcinoma A549 xenograft in nude mice. The mechanism was associated with a G(2)/M phase arrest followed by apoptosis, including membrane blebbing, loss of mitochondrial membrane potential, externalization of phosphatidylserine, chromosome condensation and DNA fragmentation. Western blot analysis showed that the intrinsic pathway was involved in Mere15-induced apoptosis. These results suggest that Mere15 may have therapeutic potential for the treatment of non-small-cell lung carcinoma.Experimental Biology and Medicine 04/2012; 237(4):442-50. · 2.64 Impact Factor -
Article: Phylogenetic analysis and screening of antimicrobial and cytotoxic activities of moderately halophilic bacteria isolated from the Weihai Solar Saltern (China)
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ABSTRACT: A total of 45 moderately halophilic bacteria was isolated from sediment and saline water collected from the Weihai Solar Saltern (China). The phylogenetic position of all the isolated strains was determined by 16S rRNA sequencing. The halophilic strains were tested for their antimicrobial activity. Cytotoxicity assay was performed to determine which of the halophilic strains could inhibit proliferation of human hepatocellular carcinoma Bel 7402 cells. Our results showed that all of the isolated 45 strains displayed moderately halophilic characteristics. Phylogenetic analysis indicated that 17 of the isolated strains were related to the phylum Firmicutes and belonged to four genera, Bacillus, Halobacillus, Planococcus and Salinicoccus. The other strains identified as genus of Halomonas belonged to phylum γ-Proteobacteria. Most of the halophilic bacterial strains showed potent activities against Gram-positive bacteria, human pathogenic fungi and plant pathogenic fungi. In addition, the crude extracts from 14 halophilic bacterial strains showed cytotoxic activity against tumor cells Bel 7402, and five of them showed remarkable activities with IC50 less than 40μgml−1. Our results suggest that the moderately halophilic bacteria may be developed as promising sources for the discovery of novel bioactive substances. KeywordsModerately halophilic bacteria-Phylogenetic analysis-Antimicrobial activity-Cytotoxic activity-Solar salternWorld Journal of Microbiology and Biotechnology 04/2012; 26(5):879-888. · 1.53 Impact Factor -
Article: Marine bromophenol bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, induces mitochondrial apoptosis in K562 cells and inhibits topoisomerase I in vitro.
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ABSTRACT: Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a marine bromophenol compound derived from marine algae. Previous reports have shown that BDDE possesses cytotoxic activity. However, the mechanisms of its apoptotic activity as well as its potential cellular targets remain unclear. The present study demonstrated that BDDE displays broad-spectrum in vitro anticancer capabilities and exhibits potent apoptotic activity in K562 cells via mitochondrial pathway. Further study revealed that BDDE inhibits the activity of topoisomerase I but does not stimulate the formation of topoisomerase I-DNA complex nor intercalate into DNA. Ethidium bromide displacement fluorescence assay and molecular modeling results showed that BDDE mainly targets DNA and binds to DNA minor groove, and thereafter inhibits the activity of topoisomerase I. The results of this study indicated that BDDE, which has unique chemical structure different from current topoisomerase I inhibitors, could serve as a lead template for rational drug design and for future anticancer agents development.Toxicology Letters 03/2012; 211(2):126-34. · 3.23 Impact Factor -
Article: Induction of Apoptosis, G0/G1 Phase Arrest and Microtubule Disassembly in K562 Leukemia Cells by Mere15, a Novel Polypeptide from Meretrix meretrix Linnaeus.
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ABSTRACT: Mere15 is a novel polypeptide from Meretrix meretrix Linnaeus with cytotoxicity in solid cancer cells. In this study, we investigated its activity on human K562 chronic myelogenous leukemia cells. Mere15 inhibited the growth of K562 cells with IC(50) values of 38.2 μg/mL. Mere15 also caused concentration dependent induction of apoptosis, with overproduction of reactive oxygen species and loss of mitochondrial membrane potential. Moreover, Mere15 arrested cell cycle progression at G(0)/G(1) phase of K562 cells in a concentration dependent manner. In addition, Mere15 caused the disassembly of the microtubule cytoskeleton in K562 cells and inhibited the polymerization of tubulin in a cell free system via interaction with tubulin. We concluded that Mere15 was cytotoxic to K562 leukemia cells and the cytotoxicity was related to the apoptosis induction, cell cycle arrest and microtubule disassembly. These results implied that Merer15 was a broad spectrum anticancer polypeptide, not only cytotoxic to various solid cancer cells but also to the chronic myelogenous leukemia cells. Mere15 may have therapeutic potential for the treatment of leukemia.Marine Drugs 01/2012; 10(11):2596-607. · 3.85 Impact Factor -
Article: Bromophenols in marine algae and their bioactivities.
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ABSTRACT: Marine algae contain various bromophenols that have been shown to possess a variety of biological activities, including antioxidant, antimicrobial, anticancer, anti-diabetic, and anti-thrombotic effects. Here, we briefly review the recent progress of these marine algal biomaterials, with respect to structure, bioactivities, and their potential application as pharmaceuticals.Marine Drugs 01/2011; 9(7):1273-92. · 3.85 Impact Factor -
Article: Synthesis and α-glucosidase inhibitory mechanisms of bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, a potential marine bromophenol α-glucosidase inhibitor.
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ABSTRACT: Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE), derived from the marine algae, is a potential α-glucosidase inhibitor for type 2 diabetes treatment. In the present study, a synthetic route was established as a valid approach to obtain BDDE. Fluorescence spectra, circular dichroism spectra and molecular docking methods were employed to elucidate the inhibitory mechanisms of BDDE against α-glucosidase. The results showed that BDDE could be prepared effectively and efficiently with the established synthetic methods. Synthetic BDDE bound with α-glucosidase and induced minor conformational changes of the enzyme. The docking results indicated the interaction between BDDE and α-glucosidase was driven by both hydrophobic forces and hydrogen bonds. The docked BDDE molecule was completely buried in the α-glucosidase binding pocket with part of the molecule reaching the catalytic center and overlapping with the position of glucose, and the rest of the molecule extending towards protein surface. This study provides useful information for the understanding of the BDDE-α-glucosidase interaction and for the development of novel α-glucosidase inhibitors.Marine Drugs 01/2011; 9(9):1554-65. · 3.85 Impact Factor -
Article: Role of microRNA-26b in glioma development and its mediated regulation on EphA2.
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ABSTRACT: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the expression of multiple target genes. Deregulation of miRNAs is common in human tumorigenesis. Low level expression of miR-26b has been found in glioma cells. However, its underlying mechanism of action has not been determined. Real-time PCR was employed to measure the expression level of miR-26b in glioma patients and cells. The level of miR-26b was inversely correlated with the grade of glioma. Ectopic expression of miR-26b inhibited the proliferation, migration and invasion of human glioma cells. A binding site for miR-26b was identified in the 3'UTR of EphA2. Over-expression of miR-26b in glioma cells repressed the endogenous level of EphA2 protein. Vasculogenic mimicry (VM) experiments were performed to further confirm the effects of miR-26b on the regulation of EphA2, and the results showed that miR-26b inhibited the VM processes which regulated by EphA2. This study demonstrated that miR-26b may act as a tumor suppressor in glioma and it directly regulates EphA2 expression. EphA2 is a direct target of miR-26b, and the down-regulation of EphA2 mediated by miR-26b is dependent on the binding of miR-26b to a specific response element of microRNA in the 3'UTR region of EphA2 mRNA.PLoS ONE 01/2011; 6(1):e16264. · 4.09 Impact Factor -
Article: Synthesis of butyl-isobutyl-phthalate and its interaction with α-glucosidase in vitro.
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ABSTRACT: Butyl-isobutyl-phthalate (BIP), isolated from the rhizoid of Laminaria japonica, is a potential α-glucosidase inhibitor for Type II diabetes treatment. In the present study, a synthetic route was established as a useful approach to obtain enough BIP. Fluorescence analysis, circular dichroism spectra and molecular docking methods were employed to elucidate the underlying molecular mechanisms of BIP inhibition on α-glucosidase. The results revealed that BIP could be synthesized in two steps and the synthesized BIP bound with α-glucosidase and induced conformational changes of the enzyme. The interaction between BIP and α-glucosidase was driven by both hydrophobic forces and hydrogen bond. The docking results indicated that the benzene ring and the isopropyl group of the BIP could fit into the hydrophobic pocket composed of Phe177, Phe157, Leu176, Leu218, Ala278 and the propyl group fitted into another nearby hydrophobic pocket formed by Trp154, Pro240, Leu174 and Ala162, respectively. This study provides useful information for the understanding of the BIP-α-glucosidase interaction and development of new α-glucosidase inhibitors.Journal of biochemistry 01/2011; 149(1):27-33. · 1.95 Impact Factor -
Article: CI431, an Aqueous Compound from Ciona intestinalis L., Induces Apoptosis through a Mitochondria-Mediated Pathway in Human Hepatocellular Carcinoma Cells.
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ABSTRACT: In the present studies, a novel compound with potent anti-tumor activity from Ciona intestinalis L. was purified by acetone fractionation, ultrafiltration, gel chromatography and High Performance Liquid Chromatography. The molecular weight of the highly purified compound, designated CI431, was 431Da as determined by HPLC-MS analysis. CI431 exhibited significant cytotoxicity to several cancer cell types. However, only a slight inhibitory effect was found when treating the benign human liver cell line BEL-7702 with the compound. To explore its mechanism against hepatocellular carcinoma, BEL-7402 cells were treated with CI431 in vitro. We found that CI431 induced apoptotic death in BEL-7402 cells in a dose- and time-dependent manner. Cell cycle analysis demonstrated that CI431 caused cell cycle arrest at the G2/M phase, and a sub-G1 peak appeared after 24 h. The mitochondrial-mediated pathway was implicated in this CI431-induced apoptosis as evidenced by the disruption of mitochondrial membrane potential. The results suggest that the CI431 induces apoptosis in BEL-7402 human hepatoma cells by intrinsic mitochondrial pathway.Evidence-based Complementary and Alternative Medicine 01/2011; 2011:292873. · 4.77 Impact Factor -
Article: α-Glucosidase inhibition and the in vivo hypoglycemic effect of butyl-isobutyl-phthalate derived from the Laminaria japonica rhizoid.
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ABSTRACT: The rhizoid of Laminaria japonica is widely used in Chinese medicine as a treatment for diabetes. Therefore, a bioactivity-tailored isolation and detailed chemical characterization was used to identify the antidiabetes compounds found in the L. japonica rhizoid. Liquid chromatography/mass spectrometry (LC/MS), proton NMR and carbon NMR spectra analyses demonstrated that the active compound was butyl-isobutyl-phthalate (BIP). BIP demonstrated a significant concentration-dependent, non-competitive inhibitory activity against α-glucosidase in vitro, with an IC(50) of 38 μm. In vivo, the ethyl acetate fraction (EAF) and purified BIP displayed a significant hypoglycemic effect in streptozocin-induced diabetic mice. The present study indicates BIP could be considered as an α-glucosidase inhibitor and developed as an important antidiabetes agent for type II diabetes therapy.Phytotherapy Research 11/2010; 24(11):1588-91. · 2.09 Impact Factor -
Article: Recovery of recombinant zebrafish p53 protein from inclusion bodies and its binding activity to p53 mRNA in vitro.
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ABSTRACT: p53 protein is an important regulation factor that can bind to p53 mRNA to regulate its translation in human and murine. To determine if a similar interaction exists in zebrafish and if the interaction affects zebrafish development, we cloned and expressed p53 protein from zebrafish in Escherichia coli. Soluble p53 protein with high purity was successfully obtained using the optimized renaturation approach. Results of a UV-crosslinking experiment and immunoprecipitation:RT-PCR analysis confirmed that the purified p53 protein could bind specifically to its cognate mRNA. Our results suggest that selecting a suitable buffer is important for renaturing p53 protein from inclusion bodies. We also demonstrated a specific interaction between p53 and it own RNA in zebrafish. Measurement of the binding activity may be a useful approach for identifying the activity of recombinant p53 protein in vitro.Protein Expression and Purification 04/2010; 72(2):262-6. · 1.59 Impact Factor -
Article: Targeting cellular proapoptotic molecules for developing anticancer agents from marine sources.
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ABSTRACT: Apoptosis as a form of programmed cell death is a critical defense mechanism against the formation and progression of cancer and exhibits distinct morphological and biochemical traits. In an in vivo situation, apoptosis functions to eliminate potentially deleterious cells without causing such adverse effects as inflammatory response and ensuing scar formation. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents. Marine natural products have become an important source in the discovery of antitumor drugs, especially when modern technology makes it more and more feasible to collect organisms from seas. Although lack of an analog of a long ethno-medical history for finding clues, as compared with terrestrial habitats, still hinders the progress, an increasing number of compounds have been isolated from marine organisms that have been found to possess apoptosis-inducing and anticancer activities. This primer summarizes several such compounds, based on their effects on apoptotic signaling pathways, although most of these products have not yet been studied in depth for their mechanisms of action.Current drug targets 03/2010; 11(6):708-15. · 3.93 Impact Factor -
Article: Interaction between thymidylate synthase and its cognate mRNA in zebrafish embryos.
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ABSTRACT: Thymidylate synthase (TS), which catalyzes the de novo synthesis of dUMP, is an important target for cancer therapy. In this report, the effects of 5-fluorouracil (5-FU) and ZD1694 on the regulation of TS gene expression were evaluated in zebrafish embryos. Our results revealed that the expression of TS was increased by about six-fold when embryos were treated with 1.0 microM 5-FU and there was a greater than 10-fold increase in the TS protein level after treatment with 0.4 microM ZD1694. Northern blot analysis confirmed that expression of TS mRNA was identical in treated or untreated embryos. Gel shift and immunoprecipitation assays revealed that zebrafish TS was specifically bound with its cognate mRNA in vitro and in vivo. We identified a 20 nt RNA sequence, TS:N20, localized to the 5'-UTR of TS mRNA, which corresponded to nt 13-32; TS:N20 bound to the TS protein with an affinity similar to that of the full-length TS mRNA. The MFold program predicted that TS:N20 formed a stable stem-loop structure similar to that of the cis-acting element found in human TS mRNA. Variant RNAs with either a deletion or mutation in the core motif of TS:N20 were unable to bind to the TS protein. In vitro translation experiments, using the rabbit lysate system, confirmed that zebrafish TS mRNA translation was significantly repressed when an excess amount of TS protein was included in the system. Additionally, a TS stability experiment confirmed that treatment of zebrafish embryos with 5-FU could increase the TS stability significantly, and the half life of TS protein was about 2.7 times longer than in untreated embryos. Our study revealed a structural requirement for the interaction of TS RNA with TS protein. These findings also demonstrated that the increase in TS protein induced by 5-FU occurs at the post-transcriptional level and that increased stability and translation efficiency both contributed to the increase in TS protein levels induced by TS inhibitors.PLoS ONE 01/2010; 5(5):e10618. · 4.09 Impact Factor
Top co-authors
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Institutions
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2009–2013
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Chinese Academy of Sciences
- Institute of Oceanology
Beijing, Beijing Shi, China
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2012
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Shandong Academy of Sciences
Jinan, Shandong Sheng, China
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