• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.400-406
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• 2015

MicroRNAs (miRNAs) are a family of non-coding RNA that are able to adjust the expression of many proteins, including ATP-binding cassette transporter and organic cation transporter. We sought to evaluate the effect of miR-511 on the regulation of OATP1B1 expression by free fatty acids. When using free fatty acids to stimulate Chang liver cells, we found that the expression of miR-511 increased significantly while the expression of OATP1B1 decreased. We also proved that SLCO1B1 is the target gene of miR-511 with a bioinformatics analysis and using the dual luciferase reporter assay. Furthermore, the expressions of SLCO1B1 and OATP1B1 decreased if transfecting Chang liver cells with miR-511, but did not increase when transfecting the inhibitors of miR-511 into steatosis cells. Our study indicates that miR-511 may play an important role in the regulation of OATP1B1 expression by free fatty acids.

• Korean Journal of Environmental Agriculture
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• v.31 no.1
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• pp.30-36
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• 2012

BACKGROUND: The resistance of rice bakanae disease pathogens against the fungicide prochloraz has been reported. Understanding the resistance mechanisms is an important for better control of the pathogens. In the present study, we investigated the resistance mechanisms of Fusarium fujikuroi CF337 (CF337) against prochloraz. METHODS AND RESULTS: Morphological changes in the cell wall of CF337 grown in potato dextrose broth (PDB) with or without prochloraz was investigated by transmission electron microscopy. Growth inhibition of CF337 was examined in PDB containing prochloraz or an ABC transporter inhibitor or both of them. Cell wall thickness of CF337 grown in PDB with prochloraz was significantly increased from $80.73{\pm}1.99nm$ to $193.11{\pm}7.07nm$. Significant inhibition in the growth of CF337 was observed in the presence of both prochloraz and the inhibitor, but no growth inhibition was observed in the presence of the inhibitor or prochloraz. Sequence analysis of ATP-binding cassette transporter (ABC) gene of CF337 showed 70 to 80% similarities to the genes of the pathogens resistant to other fungicides. CONCLUSION: Efflux transporter system and changes in cell wall thickness were suggested as resistance mechanisms of CF337 against prochloraz.

• Journal of Radiation Protection and Research
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• v.20 no.2
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• pp.71-78
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• 1995

To develop methods to reduce radiation risk and apply such knowledge to improvement of radiation protection, the effects of cobaltous chloride known as bioantimutagen on the function of E. coli RecA protein involved in the repair of DNA damage were examined. The results demonstrated two distinct effects of cobaltous chloride on the RecA protein function necessary for the strand exchange reaction. Cobaltous chloride enhanced the ability of RecA protein to displace SSB protein from single-stranded DNA and the duplex DNA-dependent ATPase activity. RecA protein was preferentially bound with UV-irradiated supercoiled DNA as compared with nonirradiated DNA The binding of RecA protein to UV-irradiated supercoiled DNA was enhanced in a dose-dependent manner. It is likely that studies on the factors affecting repair efficiency and the DNA repair proteins may provide information on the repair of ionizing radiation-induced DNA damage and the mechanism for DNA radioprotection.

• Molecules and Cells
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• v.24 no.2
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• pp.210-214
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• 2007

The 90-kDa heat shock protein (HSP90) normally functions as a molecular chaperone participating in folding and stabilizing newly synthesized proteins, and refolding denatured proteins. The HSP90 inhibitor geldanamycin (GA) occupies the ATP/ADP binding pocket of HSP90 so inhibits its chaperone activity and causes subsequent degradation of HSP90 client proteins by proteasomes. Here we show that GA reduces the level of endogenous c-Jun in human embryonic kidney 293 (HEK293) cells in a time and dose dependent manner, and that this decrease can be reversed by transfection of HSP90 plasmids. Transfection of HSP90 plasmids in the absence of GA increases the level of endogenous c-Jun protein, but has no obvious affect on c-Jun mRNA levels. We also showed that HSP90 prolongs the half-life of c-Jun by stabilizing the protein; the proteasome inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) blocks the degradation of c-Jun promoted by GA. Transfection of HSP90 plasmids did not obviously alter phosphorylation of c-Jun, and a Jun-2 luciferase activity assay indicated that over-expression of HSP90 elevated the total protein activity of c-Jun in HEK293 cells. All our evidence indicates that HSP90 stabilizes c-Jun protein, and so increases the total activity of c-Jun in HEK293 cells.

• Journal of Microbiology and Biotechnology
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• v.9 no.4
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• pp.488-497
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• 1999

Probing Streptomyces albus ATCC 21838 chromosomal DNA with a proline tRNA sequence resulted in an isolation of a putative integrating element in the 6.4-kb EcoRI fragment. It was found that Streptomyces lividans TK-24 transformed with a cloned DNA fragment on a multicopy plasmid, produced a higher level of spore pigment and mycelial red pigment on a regeneration agar. Furthermore, the transformant S. lividans TK-24 produced a markedly increased level of undecylprodigiosin in a broth culture. A nucleotide sequence analysis of the cloned region revealed several open reading frames homologous to the integrases of integrating plasmids or temperate bacteriophages, signal-transducing regulatory proteins with a conserved ATP-binding domain, oxidoreductases ($\beta$-ketoacyl reductase), and an AraC-like transcriptional regulator. To examine the effect on antibiotic production, each coding region was overexpressed separately from the other genes in the region in S. lividans TK-24 with; pJHS3044 for the expression of the signal-transducing regulatory protein homologue, pJHS3045 for the homologue of oxidoreductase, and pJHS3051 for the homologue of the AraC-like transcriptional regulator. Phenotypic studies of S. lividans TK-24 strains harboring plasmids for the overexpression of individual genes suggested the following effects of the genes on antibiotic production: The oxidoreductase homologue stimulated the production of actinorhodin and undecylprodigiosin, which was influenced by the culture conditions; the homologue of the AraC-like transcriptional regulator was the most effective factor in antibiotic production within all the culture conditions tested; the signal-transducing regulatory protein homologue repressed the effect due to the homologue of the AraC-like transcriptional regulator, however, the antibiotic production was derepressed upon entering the stationary phase.

• Genomics & Informatics
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• v.12 no.4
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• pp.231-235
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• 2014

Elevated serum uric acid levels are associated with a variety of adverse health outcomes, including gout, hypertension, diabetes mellitus, metabolic syndrome, and cardiovascular diseases. Several genome-wide association studies on uric acid levels have implicated the ATP-binding cassette, subfamily G, member 2 (ABCG2) gene as being possibly causal. We investigated an association between the single-nucleotide polymorphism (SNP) rs2725220 in the ABCG2 gene and uric acid levels in the Korean population. A total of 991 subjects in Seoul City were used for a replication study with ABCG2 SNP rs2725220. The rs2725220 SNP in the ABCG2 gene was associated with mean uric acid levels (effect per allele 0.25 mg/dL, p < 0.0001). Subjects with the GC/CC genotype had a 1.78-fold (range, 1.22- to 2.62-fold) higher risk of having abnormal uric acid levels (${\geq}7.0mg/dL$) than subjects with the GG genotype. When analyzed by gender, the association with ABCG2 was stronger in men than in women. The association with ABCG2 was much stronger in male subjects with body mass index (BMI) ${\geq}26.4$ (odds ratio, 5.09; 95% confidence interval, 2.41 to 10.8) than in male subjects with BMI < 26.4. This study clearly demonstrates that genetic variations in ABCG2 influence uric acid levels in Korean adults.

• BMB Reports
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• v.40 no.1
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• pp.72-81
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• 2007

In order to screen the aging related proteins in human normal colon epithelia, the comparative proteomics analysis was applied to get the two-dimensional electrophoresis (2-DE) profiles with high resolution and reproducibility from normal colon epithelial tissues of young and aged people. Differential proteins between the colon epithelia of two age groups were found with PDQuest software. The thirty five differential protein-spots were identified by peptide mass fingerprint (PMF) based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) and database searching. Among them there are sixteen proteins which are significantly up-regulated in the colonic mucosal epithelia of young people group, which include ATP synthase beta chain, electron transfer flavoprotein alpha-subunit, catalase, glutathione peroxidase 1, annexin A2 and heat shock cognate 71 kDa protein, etc.; There are nineteen proteins which are significantly up-regulated in the colonic mucosal epithelia of aged people group, which include far upstream element-binding protein 1, nucleoside diphosphate kinase B, protein disulfide-isomerase precursor and VDAC-2, etc.. The identified differential proteins appear to be involved in metabolism, energy generation, chaperone, antioxidation, signal transduction, protein folding and apoptosis. The data will help to understand the molecular mechanisms of human colon epithelial aging.

• Bulletin of the Korean Chemical Society
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• v.33 no.4
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• pp.1123-1127
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• 2012

P-gp (P-glycoprotein) is a member of the ATP binding cassette (ABC) family of transporters. It transports many kinds of anticancer drugs out of the cell. It plays a major role as a cause of multidrug resistance (MDR). MDR function may be a cause of the failure of chemotherapy in cancer and influence pharmacokinetic properties of many drugs. Hence classification of candidate drugs as substrates or nonsubstrate of the P-gp is important in drug development. Therefore to identify whether a compound is a P-gp substrate or not, in silico method is promising. Recursive Partitioning (RP) method was explored for prediction of P-gp substrate. A set of 261 compounds, including 146 substrates and 115 nonsubstrates of P-gp, was used to training and validation. Using molecular descriptors that we can interpret their own meaning, we have established two models for prediction of P-gp substrates. In the first model, we chose only 6 descriptors which have simple physical meaning. In the training set, the overall predictability of our model is 78.95%. In case of test set, overall predictability is 69.23%. Second model with 2D and 3D descriptors shows a little better predictability (overall predictability of training set is 79.29%, test set is 79.37%), the second model with 2D and 3D descriptors shows better discriminating power than first model with only 2D descriptors. This approach will be used to reduce the number of compounds required to be run in the P-gp efflux assay.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.161-167
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• 2020

Background: The ascomycete fungi Cylindrocarpon destructans (Cd) and Fusarium solani (Fs) cause ginseng root rot and significantly reduce the quality and yield of ginseng. Cd produces the secondary metabolite radicicol, which targets the molecular chaperone Hsp90. Fs is resistant to radicicol, whereas other fungal genera associated with ginseng disease are sensitive to it. Radicicol resistance mechanisms have not yet been elucidated. Methods: Transcriptome analyses of Fs and Cd mycelia treated with or without radicicol were conducted using RNA-seq. All of the differentially expressed genes (DEGs) were functionally annotated using the Fusarium graminearum transcript database. In addition, deletions of two transporter genes identified by RNA-seq were created to confirm their contributions to radicicol resistance. Results: Treatment with radicicol resulted in upregulation of chitin synthase and cell wall integrity genes in Fs and upregulation of nicotinamide adenine dinucleotide dehydrogenase and sugar transporter genes in Cd. Genes encoding an ATP-binding cassette transporter, an aflatoxin efflux pump, ammonium permease 1 (mep1), and nitrilase were differentially expressed in both Fs and Cd. Among these four genes, only the ABC transporter was upregulated in both Fs and Cd. The aflatoxin efflux pump and mep1 were upregulated in Cd, but downregulated in Fs, whereas nitrilase was downregulated in both Fs and Cd. Conclusion: The transcriptome analyses suggested radicicol resistance pathways, and deletions of the transporter genes indicated that they contribute to radicicol resistance.

• Molecules and Cells
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• v.43 no.1
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• pp.48-57
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• 2020

The microalga Chlamydomonas reinhardtii accumulates triacylglycerols (TAGs) in lipid droplets under stress conditions, such as nitrogen starvation. TAG biosynthesis occurs mainly at the endoplasmic reticulum (ER) and requires fatty acid (FA) substrates supplied from chloroplasts. How FAs are transferred from chloroplast to ER in microalgae was unknown. We previously reported that an Arabidopsis thaliana ATP-binding cassette (ABC) transporter, AtABCA9, facilitates FA transport at the ER during seed development. Here we identified a gene homologous to AtABCA9 in the C. reinhardtii genome, which we named CrABCA2. Under nitrogen deprivation conditions, CrABCA2 expression was upregulated, and the CrABCA2 protein level also increased. CrABCA2 knockdown lines accumulated less TAGs and CrABCA2 overexpression lines accumulated more TAGs than their untransformed parental lines. Transmission electron microscopy showed that CrABCA2 was localized in swollen ER. These results suggest that CrABCA2 transports substrates for TAG biosynthesis to the ER during nitrogen starvation. Our study provides a potential tool for increasing lipid production in microalgae.