• Korean journal of applied entomology
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• 제59권4호
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• pp.341-348
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• 2020

The ATP-binding cassette (ABC) transporter superfamily represents the largest transmembrane protein that transports a variety of substrates across extra- and intra-cellular membranes. In insects, the ABC transporter proteins play crucial roles in insecticide resistance. To date, no studies have investigated the involvement of ABC transporter gene for cross-resistance to insecticide chemistries. Here, we studied such possible mechanisms against six conventional insecticides using transgenic Drosophila melanogaster strains carrying Mdr49 transcript variant A. For the 91-R and 91-C strains of Drosophila melanogaster, although they have a common origin, 91-R has been intensely selected with DDT for over 60 years, while 91-C has received no insecticide selection. Our transgenic analyses showed that overexpression of 91-R-MDR49 transcript variant A along with three amino acid variations can yield a relatively low degree of cross-resistance to carbofuran (2.0~6.7-fold) and permethrin (2.5~10.5-fold) but did not show cross-resistance to abamectin, imidacloprid, methoxychlor, and prothiofos as compared to the Gal4-driver control strain without transgene expression. These results indicate that the overexpression of Mdr49A in itself leads to a cross-resistance and three amino acid changes have additional effects on positive cross-resistance to carbofuran and permethrin.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3213-3217
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• 2013

Background: P-glycoprotein (Pgp), encoded by the multidrug resistance 1 (MDR1) gene, is an efflux transporter which plays an important role in pharmacokinetics. The current preliminary study was designed to determine associations between a germ-line polymorphism in the MDR1 gene with differentiated thyroid carcinoma (DTC). Materials and Methods: In the current case-control study, 60 differentiated thyroid cancers (DTC)- 45 papillary TC (PTC), 9 follicular TC(FTC) and 6 well-differentiated tumors of uncertain malignant potential (WDT-UMP) were examined. Results were compared to a healthy control group (n=58) from the same population. Genomic DNA was extracted from peripheral blood with EDTA and the target gene was genotyped by real-time PCR. Results: Carriers of the variant allele of MDR1 exon 26 polymorphism were at 2.8-fold higher risk of DTC than the control group (odds ratio [OR]: 0.3805, 95% confidence interval [Cl]: 0.1597-0.9065 (p> 0.046). Conclusions: Presented results suggest that the MDR1 3435TT genotype might influence risk of development of DTC and that the CC genotype might be linked to a poor prognosis. Large-scale studies are now needed to validate this association.

• Korean Journal of Biological Psychiatry
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• 제9권1호
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• pp.34-41
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• 2002

Background:Since serotonin neurotrasnmission plays an important role in the pathophysiology of depression, the drug that acts on serotonin transporter can be an effective antidepressant. The aim of this study was to investigate the relationship between serotonin transporter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. Method:The 175 depressive patients, who met DSM-IV criteria for major depressive disorder or dysthymic disorder were enrolled into three year study. The genotypes of the patients were investigated by polymerase chain reaction of genomic DNA with promoter regions of the serotonin transporter gene. The patients were assessed by the Clinical Global Impression Scale, at the 1st visit, 8th week, 16th week, 1st year, 2nd and 3rd year after the antidepressant treatment. Result:The genotypes of 138 patients were investigated and 128 of them finished this 1st year study and 107 remained in the study after 2-year treatment, and, 97 completed this 3-year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better antidepressant therapeutic response than heterozygote(l/s). The heterozygote(l/s) showed a better response than the subset with homozygote(s/s) of short variant at 1st, 2nd and 3rd year after the antidepressant treatment in CGI-global improvement score. Conclusion:This result shows that the serotonin transporter polymorphism may be related to the long-term effect of antidepressant treatment and there may be also ethnic difference.

• Korean Journal of Environmental Agriculture
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• 제31권1호
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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.

• Archives of Pharmacal Research
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• 제29권10호
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• pp.911-920
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• 2006

Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around $10\;{\mu}M$. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, ${\gamma}-GCS$, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.

• Korean Journal of Biological Psychiatry
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• 제16권1호
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• pp.25-36
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• 2009

Objectives : The aim of this study was to investigate the association between Korean ADHD patients and the l/s polymorphism of serotonin transporter(5-HTTLPR). Methods : The study sample consisted of 189 Korean ADHD children diagnosed by Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version(K-SADS-PL), both parents of ADHD children, and 150 normal children. DNA were extracted from the blood of all samples, and genotyping was done. Based on the allele and genotype information, not only the case-control analysis between ADHD and normal children but also the family-based association test among ADHD children and their parents. Transmission disequilibrium test(TDT) were performed for family-based associated test(number of trio=113). The results of the clinical rating and neuropsychological tests were compared according to the l/s genotype of ADHD children. Results : In case-control analysis, there were no statistically significant difference of l/s gene polymorphism between ADHD and normal children in various kinds of analysis condition. In family-based association study, TDT failed to detect linkage disequilibrium between l/s gene polymorphism and ADHD in whole ADHD families. However, in the families of ADHD inattentive type only(number of trio=23), I allele was transmitted more preferentially in the proband with ADHD even if the number of families was small(${\chi}^2$=4.57, p=.032). In the analysis of the results from the clinical scales and neuropsychological tests in ADHD children, the score of the Novelty- Seeking of ADHD children with l/l genotype was significantly lower than with the other genotypes(F=3.15, p=.047), and that of Self Transcendence was significantly higher(F=4.25, p=.017). Conclusion : The results of this study suggest there were no significant genetic association between the 5- HTTLPR gene polymorphism and Korean ADHD.

• Journal of Life Science
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• 제24권8호
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• pp.895-902
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• 2014

Adiponectin has been known to improve insulin sensitivity and elicit glucose uptake via increased glucose transporter 4 (GLUT4) translocation. In the current study, mRNA expression levels of adiponectin and GLUT4 were measured in subcutaneous adipose tissue from C57BL/6 mice fed normal (ND) or high-fat diet (HFD) until 16, 26, 36, 47, or 77 weeks of age starting from 6 weeks of age. Expression levels were also measured in mice with calorie restriction (CR) and in thiazolidinedione (TZD) treated mice. Using quantitative real-time PCR, we demonstrated that GLUT4 expression in adipose tissue significantly decreased in HFD mice groups and increased in CR (p<0.05) and TZD (p=0.007) groups while there was no difference in adiponectin mRNA expression levels between experimental and control groups. General linear regression models were used to assess the association of gene expression levels between adiponectin and GLUT4 and to determine whether adiponectin affects GLUT4 transcription. mRNA expression levels of adiponectin and GLUT4 are significantly associated each other in mice fed a ND (p<0.0001) or HFD (p<0.0001), in groups separated into each age and diet, and CR group (p=0.002), but not in TZD group (p=0.73). These results demonstrated that gene expression of adiponectin and GLUT4 is strongly associated, suggesting that there is a common regulatory mechanism for adiponectin and GLUT4 gene expression and/or adiponectin has a direct role in GLUT4 gene expression in adipose tissue.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 한국식물병리학회 2002년도 총회 및 추계학술발표회
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• pp.59.2-59
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• 2002

• Journal of Life Science
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• 제20권10호
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• pp.1451-1457
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• 2010

Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of cell-cell signaling in neuronal systems. The serotonin transporter (SERT) on the plasma membrane controls the extracellular 5-HT level by reuptake of released 5-HT from the synaptic cleft, but the underlying regulation mechanism is unclear. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the carboxyl (C)-terminal region of SERT and found a specific interaction with protein kinase C-$\varepsilon$ (PKC-$\varepsilon$), a PKC isotype that is characterized as a calcium-independent and phorbol ester/diacylglycerol-sensitive serine/threonine kinase. PKC-$\varepsilon$ bound to the tail region of SERT but not to other members of the $Na^+/Cl^-$ dependent SLC6 gene family in the yeast two-hybrid assay. The C-terminal region of PKC-$\varepsilon$ is essential for interaction with SERT. In addition, these proteins showed specific interactions in the glutathione S-transferase (GST) pull-down assay. PKC-$\varepsilon$ phosphorylated the peptide of the SERT amino (N)-terminus in vitro. These results suggest that the phosphorylation of SERT by PKC-$\varepsilon$ may regulate SERT activity in plasma membrane.

• Journal of Marine Life Science
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• 제1권2호
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• pp.79-87
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• 2016

Heavy metals such as cadmium (Cd) are highly toxic to aquatic organisms and human, even at trace concentration. Herein we investigated the effect of Cd on the gene expression of ATP-binding cassette (ABC) transporters and glutathione S-transferase (GST) in marine ciliate Euplotes crassus. Seven ABC transporters and one GST genes were partially cloned and sequences, and thereafter, transcriptional modulation of these genes after exposure to Cd for 8 h was investigated using quantitative real time RT- PCR (qRT-PCR). As results, sequence analysis and phylogenetic study revealed that E. crassus ABCs are likely typical ABC transports, in particular, B/C family, and GST gene may be similar to GST theta isoform. A significant increase in the expression of ABCs, except for ABCB21 was observed in a concentration dependent manner after exposure to Cd (0.1 and 0.5 mg/l) for 8 h. The GST mRNA level was the highest at 0.5 mg/l Cd and then reduced until control level. These findings suggest that ABCs and GST may be involved in a protective mechanism against Cd-mediated toxicity in E. crassus.