• Proceedings of the Korean Society for Applied Microbiology Conference
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• 2005.06a
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• pp.131-136
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• 2005

• Journal of Microbiology
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• v.35 no.4
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• pp.277-283
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• 1997

Promoters inducible by paraquat, a superocide-generating agent, were isolated from Escherichia coli using a promoter-probing plasmid pRS415 with promoterless lacA gene. Twenty one promoters induced by paraquat were selected and further characterized. From sequence analysis, thirteen of the promoters were mapped to their specific loci on the Escherichia coli chromosome. Several promoters were mapped to the upstream of known genes such as usgl, katG, and mglB, whose relationships with superoxide response have not been previously reported. Other promoters were mapped to the upstream region of unknown open reading frames. Downstream of HC 96 promoter are uncharacterized ORFs whose sequences are homologous to ABC-transporter subunits. Downstream of HC84 promoter is an ORF encoding a transcriptional regulator-like protein, which contains a LysR family-specific HTH (helix-turn-helix) DNA bindign motif. We investigated whether these promoters belong to the soxRS regulon. All promoters except HC96 were found to belong to the soxRS regulon. The HC96 promoter was significantly induced by paraquat in the soxRS deletion mutant strain. The basal transcription level of three promoters (HE43, HC71, HD94) significantly increased at the stationary phase, implying that they are regulated by RpoS. However, paraquat inducibility of all promoters disappeared in the stationary phase, suggesting that SoxRS regulatory system is active only in rapidly growing cells.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.375-385
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• 2010

Conventional cancer chemotherapy is seriously limited by tumor cells exhibiting multidrug resistance (MDR), which is caused by changes in the levels or activity of membrane transporters that mediate energy-dependent drug efflux and of proteins that affect drug metabolism and/or drug action. Cancer scientists and oncologists have worked together for some time to understand anticancer drug resistance and develop pharmacological strategies to overcome such resistance. Much focus has been on the reversal of the MDR phenotype by inhibition of ATP-binding cassette (ABC) drug transporters. ABC transporters are a family of transporter proteins that mediate drug resistance and low drug bioavailability by pumping various drugs out of cells at the expense of ATP hydrolysis. Many inhibitors of MDR transporters have been identified, and though some are currently undergoing clinical trials, none are in clinical use. Herein, we briefly review the status of MDR in human cancer, explore the pathways of MDR in chemotherapy, and outline recent advances in the design and development of MDR modulators.

• Journal of Integrative Natural Science
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• v.5 no.2
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• pp.72-78
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• 2012

Multidrug resistance is a major obstacle in cancer chemotherapy. Cancer cells efflux chemotherapeutic drug out of cell by means of transporter and reduce the active concentration of it inside cell. Such transporters are member of the ATP binding cassettes (ABC) protein. It includes P-gp, multiple resistant protein (MRP), and breast cancer resistant protein (BCRP). These proteins are widely distributed in the human cells such as kidney, lung, endothelial cells of blood brain barrier etc. However, there are number of drugs developed for it, but most of them are getting transported by it. So, still there is necessity of a good modulator, which could effectively combat the transport of chemotherapeutic agents. Natural products origin modulators were found to be effective against transporter such as flavonoids, which belongs to third generation modulators. They have advantage over synthetic inhibitor in the sense that they have simple structure and abundant in nature. This review focuses on the P-gp structure its architecture, efflux mechanism, herbal inhibitors and their mechanism of action.

• Journal of Integrative Natural Science
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• v.4 no.1
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• pp.23-30
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• 2011

Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.

• 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.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.139-153
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• 2010

Nitrosative stress is defined as pathophysiological conditions that are related to covalent modifications of proteins by nitration/nitrosylation by forms of nitrogen oxide ($NO_x$), leading to DNA damage, ultimately, cell death. This type of stress condition appears to be associated with a number of disease states, including diabetes, inflammation and neurodegenerative diseases. Since these pathological conditions are frequently chronic in nature and, thus, require long-term treatment, changes in pharmacokinetics are likely to affect the therapy. Transporters are membrane proteins that facilitate the movement of substrates, including drugs, across plasma membranes of epithelial / endothelial cells. Since it is now increasingly evident that transporters are pharmacokinetically significant, functional alteration of transporters by this stress condition may have therapeutic relevance. In this review, experimental techniques that are used to study both in vivo and in vitro nitrosative stress are summarized and discussed, along with available literature information on the functional implication of transporters under conditions of nitrosative stress conditions. In the literature, both functional induction and impa irment were apparently present for both drug transporter families [i.e., ATP-binding cassette (ABC) and solute carrier families (SLC)]. Furthermore, a change in the function of a certain transporter appears to have temporal dependency by impairment in the early phase of nitrosative stress and induction thereafter, suggesting that the role of nitrosative stress is complex in terms of functional implications of the transporters. Although the underlying mechanisms for these alterations are not fully understood, protein nitration/nitrosylation appears to be involved in the functional impairment whereas transcript factor(s) activated by nitrosative stress may play a role, at least in part, in functional induction. Interestingly, functional induction under conditions of nitrosative stress has not been observed for SLC transporters while such impairment has been documented for both ABC and SLC transporters. Further investigations appear to be necessary to fully delineate the underlying reasons for these differences on the impact and importance of nitrosative stress conditions.

• Journal of Life Science
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• v.23 no.1
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• pp.8-14
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• 2013

Genes expressed during conidial germination of the pepper anthracnose fungus Colletotrichum acutatum were identified by sequencing the 5' end of unidirectional cDNA clones prepared from the conidial germination stage. A total of 983 expressed sequence tags (ESTs) corresponding to 464 genes, 197 contigs and 267 singletons, were generated. The deduced protein sequences from half of the 464 genes showed significant matches (e value less than 10-5) to proteins in public databases. The genes with known homologs were assigned to known functional categories. The most abundantly expressed genes belonged to those encoding the elongation factor, histone protein, ATP synthease, 14-3-3 protein, and clock controlled protein. A number of genes encoding proteins such as the GTP-binding protein, MAP kinase, transaldolase, and ABC transporter were detected. These genes are thought to be involved in the development of fungal cells. A putative pathogenicity function could be assigned for the genes of ATP citrate lyase, CAP20 and manganese-superoxide dismutase.

• 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.

• Molecules and Cells
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• v.41 no.12
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• pp.1052-1060
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• 2018

Triclosan (TCS) is a phenolic antimicrobial chemical used in consumer products and medical devices. Evidence from in vitro and in vivo animal studies has linked TCS to numerous health problems, including allergic, cardiovascular, and neurodegenerative disease. Using Caenorhabditis elegans as a model system, we here show that short-term TCS treatment ($LC_{50}$: ~0.2 mM) significantly induced mortality in a dose-dependent manner. Notably, TCS-induced mortality was dramatically suppressed by co-treatment with non-ionic surfactants (NISs: e.g., Tween 20, Tween 80, NP-40, and Triton X-100), but not with anionic surfactants (e.g., sodium dodecyl sulfate). To identify the range of compounds susceptible to NIS inhibition, other structurally related chemical compounds were also examined. Of the compounds tested, only the toxicity of phenolic compounds (bisphenol A and benzyl 4-hydroxybenzoic acid) was significantly abrogated by NISs. Mechanistic analyses using TCS revealed that NISs appear to interfere with TCS-mediated mortality by micellar solubilization. Once internalized, the TCS-micelle complex is inefficiently exported in worms lacking PMP-3 (encoding an ATP-binding cassette (ABC) transporter) transmembrane protein, resulting in overt toxicity. Since many EDCs and surfactants are extensively used in commercial products, findings from this study provide valuable insights to devise safer pharmaceutical and nutritional preparations.