• 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 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.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.5
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• pp.643-652
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• 2017

Objective: Prostaglandins (PGs) function in various reproductive processes, including luteolysis, maternal pregnancy recognition, conceptus development, and parturition. Our earlier study has shown that PG transporters ATP-binding cassette, subfamily C, member 4 (ABCC4) and solute carrier organic anion transporter family, member 2A1 (SLCO2A1) are expressed in the uterine endometrium in pigs. Since several other PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 are known to be present in the uterine endometrium, this study investigated the expression of these PG transporters in the porcine uterine endometrium and placenta. Methods: Uterine endometrial tissues were obtained from gilts on day (D) 12 and D15 of the estrous cycle and days 12, 15, 30, 60, 90, and 114 of pregnancy. Results: ABCC1, ABCC9, SLCO4C1, and SLCO5A1 mRNAs were expressed in the uterine endometrium, and levels of expression changed during the estrous cycle and pregnancy. Expression of ABCC1 and ABCC9 mRNAs was localized mainly to luminal and glandular epithelial cells in the uterine endometrium, and chorionic epithelial cells during pregnancy. Conceptuses during early pregnancy and chorioallantoic tissues from mid to late pregnancy also expressed these PG transporters. $Estradiol-17{\beta}$ increased the expression of ABCC1 and SLCO5A1, but not ABCC9 and SLCO4C1 mRNAs and increasing doses of $interleukin-1{\beta}$ induced the expression of ABCC9, SLCO4C1, and SLCO5A1 mRNAs in endometrial explant tissues. Conclusion: These data showed that several PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 were expressed at the maternal-conceptus interface, suggesting that these PG transporters may play an important role in the establishment and maintenance of pregnancy by regulating PG transport in the uterine endometrium and placenta in pigs.

• Natural Product Sciences
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• v.20 no.1
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• pp.1-6
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• 2014

P-glycoprotein (P-gp) is a permeability glycoprotein also known as multidrug resistance protein 1 (MDR1). P-gp is an ATP-binding cassette (ABC) transporter that pumps various types of drugs out of cells. These transporters reduce the intracellular concentrations of drugs and disturb drug absorption. The Caco-2 cell permeability assay system is an effective in vitro system that predicts the intestinal absorption of drugs and the functions of enzymes and transporters. Rhodamine-123 (R-123) and digoxin are well-known P-gp substrates that have been used to determine the function of P-gp. Efflux of P-gp substrates by P-gp has been routinely evaluated. To date, a number of herbal medicines have been tested with Caco-2 cell permeability assay system to assess bioavailability. There are growing efforts to find phytochemicals that potentially regulate P-gp function. The Caco-2 cell permeability assay system is a primary strategy to search for candidates of P-gp inhibitors. In this mini review, we have summarized the P-gp modulation by herbal extracts, decoctions or single components from natural products using Caco-2 cell permeability assays. Many natural products are known to regulate P-gp and herbal medicines could be used in combination with conventional drugs to enhance bioavailability.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6935-6938
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• 2014

Gastric cancer (GC) is one of the most common malignancies worldwide. The ABCB1 protein, a member of the ATP-binding cassette (ABC) transporter family, encoded by the ABCB1 gene, considerably influences the distribution of drugs across cell membranes as well as multidrug resistance (MDR) of antineoplastic drugs. In contrast to the extensive knowledge on the pharmacological action of ABCB1 protein, the correlation between the clinical-pathological data and ABCB1 protein expression in patients with GC remains unclear. The aim was to investigate association between ABCB1 expression and overall survival in GC patients. Human tumor fragments from 57 GC patients were examined by immunohistochemistry assay. We observed lower survival rate of patients with GC who were positive for ABCB1 expression (p=0.030). Based on these observations, we conclude that GC patients with positive ABCB1 protein immunohistochemical expression in their tumors suffer shorter overall survival.

• Journal of the Korean Child Neurology Society
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• v.24 no.3
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• pp.71-83
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• 2016

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ATP binding cassette subfamily D member 1 (ABCD1), a gene that encodes peroxisomal membrane located on ABC half-transporter named adrenoleukodystrophy protein (ALDP). X-ALD is characterized by a highly variable clinical spectrum, including progressive cerebral type, adrenomyeloneuropathy, and addison-only phenotype. No genotype/phenotype correlation has been established. Thus, unidentified modifier genes and other co-factors are speculated to modulate the phenotypic variation and disease severity. Recent advanced sequencing methods and reprogramming technologies not only offer an affordable and applicable approach to investigate the pathophysiological mechanisms of adrenoleukodystrophy, but also provide means to develop therapy. A causal therapy of X-ALD is lacking. Lorenzo's oil therapy is recommended for asymptomatic boys, but the longest study found that the oil was not beneficial at all to symptomatic X-ALD patients. Hematopoietic stem cell therapy has a relevant chance of success when performed during this early stage of cerebral type X-ALD. Recently, it has been insisted that lentiviral-mediated gene therapy of hematopoietic stem cells can provide clinical benefits in X-ALD. This review describes current knowledge on the clinical presentation, pathogenesis, diagnosis and management of X- ALD.

• BMB Reports
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• v.52 no.5
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• pp.330-335
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• 2019

Hepatitis B virus (HBV) encoding the HBV x protein (HBx) is a known causative agent of hepatocellular carcinoma (HCC). Its pathogenic activities in HCC include interference with several signaling pathways associated with cell proliferation and apoptosis. Mutant C-terminal-truncated HBx isoforms are frequently found in human HCC and have been shown to enhance proliferation and invasiveness leading to HCC malignancy. We investigated the molecular mechanism of the reduced doxorubicin cytotoxicity by C-terminal truncated HBx. Cells transfected with C-terminal truncated HBx exhibited reduced cytotoxicity to doxorubicin compared to those transfected with full-length HBx. The doxorubicin resistance of cells expressing C-terminal truncated HBx correlated with upregulation of the ATP binding cassette subfamily B member 1(ABCB1) transporter, resulting in the enhanced efflux of doxorubicin. Inhibiting the activity of ABCB1 and silencing ABCB1 expression by small interfering ribonucleic acid (siRNA) increased the cytotoxicity of doxorubicin. These results indicate that elevated ABCB1 expression induced by C-terminal truncation of HBx was responsible for doxorubicin resistance in HCC. Hence, co-treatment with an ABCB1 inhibitor and an anticancer agent may be effective for the treatment of patients with liver cancer containing the C-terminal truncated HBx.

• International Journal of Industrial Entomology and Biomaterials
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• v.43 no.2
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• pp.45-51
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• 2021

High blood cholesterol levels and oxidized cholesterol are risk factors for cardiovascular disease, which displays high annual incidence. Although studies on sericulture products, including pupae, silk protein, and blood lymph, as hypocholesterolemic substances have been reported, insufficient research in this field has been focused on silkworm larvae. Six larval extracts (Low temperature distilled water, LW; hot temperature distilled water, HW; and 30-100% ethanol, E30-E100) were prepared, and their effects on cholesterol metabolism were examined. LW most potently reduced the risk of cholesterol-related disorders. Polyphenols were highly represented in LW, corresponding with its increased antioxidant potency. The cholesterol biosynthesis enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) was strongly inhibited by LW. Hepatocytes over-expressed LDL receptor (LDLR) after LW stimulation, promoting cholesterol elimination from plasma. LW also increased ATP binding cassette transporter 1 (ABCA1) gene expression, upregulating HDL biogenesis. In conclusion, LW exhibited strong antioxidant activity, suppressed cholesterol biosynthesis, improved LDL uptake from plasma, and upregulated HDL biosynthesis. In aggregate, these activities could reduce blood cholesterol levels and prevent cardiovascular disease.

• BMB Reports
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• v.57 no.2
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• pp.92-97
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• 2024

Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory element-binding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.12 no.1
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• pp.49-53
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• 2012

X-linked adrenoleukodystrophy (ALD) is a rare inherited metabolic disease which results in impaired peroxisomal ${\beta}$-oxidation and the accumulation of very long chain fatty acids (VLCFA) in the adrenal cortex, the myelin of the central nervous system, and the testes. X-linked ALD is caused by mutations in the ABCD1 gene encoding an ATP-binding cassette transporter superfamily located in the peroxisomal membrane. This disease is characterized by a variety of phenotypes. The classic childhood cerebral ALD is a rapidly progressive demyelinating condition affecting the cerebral white matter before the age of 10 years in boys. We report the case of a 8-year-old with childhood cerebral X-linked ALD who developed inattention, hyperactivity, motor incoordination and hemiparesis. We diagnosed ALD with elevated plasma very long chain fatty acid level and diffuse high signal intensity lesions in both parieto-occipital white matter and cerebellar white matter in brain MRI. We identified a novel c.983delT (p.Met329CysfsX7) mutation of the ABCD1 gene. There is no correlation between X-ALD phenotype and mutations in the ABCD1 gene. Further studies for searching additional non-genetic factor which determine the phenotypic variation will be needed.