• Journal of Marine Life Science
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• v.6 no.2
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• pp.73-79
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• 2021

Bisphenol A is a representative endocrine disruptor and continuously detected in aquatic environment due to wide use, resulting in adverse effects on growth, development, and reproduction in diverse organisms as well as human. Structural analogs have been developed to substitute BPA are also suspected to have endocrine disrupting effects. In the present study, the time-dependent expression patterns of ecdysteroid synthesis (nvd, cyp314a1), receptors (EcRA, EcRB, USP, ERR), and downstream signaling pathway - related genes (HR3, E75, Vtg, VtgR) were investigated using quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) in the brackish water flea Diaphanosoma celebensis exposed to Bisphenol analogs (BPs; BPA, BPF, and BPS) for 6, 12, and 24 h. As results, the expression of nvd, cyp314a1, EcRs, USP, ERR and E75 mRNA was upregulated at 6 h exposure to BPF, which is earlier than BPA and BPS (12 h). On the other hand, HR3, E75 and VtgR mRNA levels were elevated at 6 h earlier at BPS and BPF than at BPA (12 h), but Vtg mRNA level was slightly changed within 24 h. These findings suggest that like BPA, BPF and BPS can also modulate the transcription of ecdysteroid pathway - related genes with different mechanisms, and have a potential as endocrine disruptors. This study will provide a better understanding the molecular mode of action of bisphenols on ecdysteroid pathway in the brackish water flea.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.4
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• pp.239-253
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• 2022

Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.27 no.4
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• pp.177-188
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• 2014

목적 : 본 연구에서는 백개자 열수추출물이 활성화된 대식세포 및 사람 비만세포주, HMC-1에서 염증 반응을 효과적으로 억제하는가를 관찰하고자 하였다. 방법 : 대식세포에 여러 농도의 백개자 열수추출물을 가한 뒤 LPS로 염증을 유도하여 NO 생산, iNOS와 COX-2 단백질 발현을 관찰하였으며 HMC-1에도 여러 농도의 백개자 열수추출물을 가한 후 PMACI로 염증을 유도하여 histamine 분비와 NF-${\kappa}B$ 활성 및 $I{\kappa}B$-${\alpha}$의 인산화, MAPKs pathway에 대한 저해효과를 관찰하였다. 결과 : 백개자 열수추출물은 대식세포에서 LPS로 유도된 NO 생성 및 INOS, COX-2 단백질 발현을 농도 의존적으로 저해하였으며 HMC-1에서 PMACI로 유도된 histamine의 분비와 p38 MAPK, ERK, JNK의 인산화 반응 및 $I{\kappa}B$-${\alpha}$의 인산화와 NF-${\kappa}B$의 활성을 저해하였다. 결론 : 백개자 열수추출물은 대식세포 및 비만세포의 활성을 저해함으로써 알레르기 질환의 치료에 사용될 잠재성이 크다고 사료된다.

• Bulletin of the Korean Chemical Society
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• v.35 no.1
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• pp.51-56
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• 2014

The solvolysis rate constants of 2,4-dimethoxybenzenesulfonyl chloride (1) in 30 different solvents are well correlated with the extended Grunwald-Winstein equation, using the $N_T$ solvent nucleophilicity scale and $Y_{Cl}$ solvent ionizing scale, with sensitivity values of $0.93{\pm}0.14$ and $0.65{\pm}0.06$ for l and m, respectively. These l and m values can be considered to support a $S_N2$ reaction pathway. The activation enthalpies (${\Delta}H^{\neq}$) were 12.4 to $14.6kcal{\cdot}mol^{-1}$ and the activation entropies (${\Delta}S^{\neq}$) were -15.5 to -$32.3kcal{\cdot}mol^{-1}{\cdot}K^{-1}$, which is consistent with the proposed bimolecular reaction mechanism. The solvent kinetic isotope effects (SKIE) were 1.74 to 1.86, which is also in accord with the $S_N2$ mechanism and was possibly assisted using a general-base catalysis. The values of product selectivity (S) for solvolyses of 1 in alcohol/water mixtures was 0.57 to 6.5, which is also consistent with the proposed bimolecular reaction mechanism. Third-order rate constants, $k_{ww}$ and $k_{aa}$, were calculated from the rate constants ($k_{obs}$), together with $k_{aw}$ and $k_{wa}$ calculated from the intercept and slope of the plot of 1/S vs. [water]/[alcohol]. The calculated rate constants, $k_{calc}$ ($k_{ww}$, $k_{aw}$, $k_{wa}$ and $k_{aa}$), are in satisfactory agreement with the experimental values, supporting the stoichiometric solvation effect analysis.

• Journal of the Korean Chemical Society
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• v.37 no.8
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• pp.695-701
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• 1993

Rate constants of solvolysis of 2-thiophenesulfonyl chloride were determined in aqueous binary mixtures with methanol, ethanol, acetone in water and in methanol. These data are interpreted using the equation of Grunwald-Winstein and Kivinen relationship. Also, kinetic solvent isotope effects in water and in methanol and product selectivities in alcohol-water mixtures were determined. Kinetic solvent isotope effect for hydrolysis of 2-thiopenesulfonyl chloride was 2.24 and 1.47 for methanol and water, respectively. Selectivity values for formation of ester relative to acid in ethanol-water mixtures show maximum S value. From kinetic solvent isotope effect in methanol and water, selectivity data in aqueous alcoholic solvents and solvent effects, it is proposed that the reaction channel favoured in low polarity solvents is general-base catalysis and/or is possibly addition elimination (S$_A$N) reaction pathway and in high polarity solvents iS S$_N$2 reaction mechanism.

• Parasites, Hosts and Diseases
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• v.56 no.2
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• pp.135-145
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• 2018

Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- rich-repeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, $CK2{\beta}$, VEGF, GCL, GST and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.

• Asian-Australasian Journal of Animal Sciences
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• v.13 no.6
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• pp.748-756
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• 2000

Effects of xanthine (X), xanthine oxidase (XO), and catalase (C), $H_2O_2$, and carbohydrates on sperm capacitation, acrosome reaction, and fertilizing ability in vitro were examined. Glucose alone, but not fructose, supported the maximum rate of sperm capacitation and acrosome reaction. However, in the combination of X, XO, and C (XXOC) or $H_2O_2$, fructose alone also supported maximum capacitation, acrosome reaction, and fertilization. Either insufficient or excessive amounts of $H_2O_2$ decreased sperm capacitation and the acrosome reaction. In order to understand how glucose generates $H_2O_2$ or other reactive oxygen species in sperm cells, 6-aminonicotinamide, an inhibitor of the pentose-phosphate pathway (PPP), and apocynin, an inhibitor of NADPH oxidase, were added to sperm suspensions in glucose-containing medium. Results appeared that sperm capacitation, acrosome reaction, and fertilization were consequently inhibited by either one of these compounds. These inhibitory effects were nullified by addition of XXOC. These results support the hypothesis that glucose, in addition to being a substrate for glycolysis, facilitates sperm capacitation and the acrosome reaction by generating reactive oxygen species through G-6-P dehydrogenase and NADPH oxidase.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.453-460
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• 2020

Background: BIOGF1K, a fraction of Panax ginseng, has desirable antimelanogenic, anti-inflammatory, and antiphotoaging properties that could be useful for treating skin conditions. Because its potential positive effects on allergic reactions in skin have not yet been described in detail, this study's main objective was to determine its efficacy in the treatment of atopic dermatitis (AD). Methods: High-performance liquid chromatography was used to verify the compounds in BIOGF1K, and we used the (3-4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide method to determine its cytotoxicity in RBL-2H3 and HMC-1 cell lines. RBL-2H3 cells were induced using both anti-DNP-IgE/DNP-BSA and calcium ionophore (A2187) treatments, whereas HMC-1 cells were induced using A2187 alone. To measure mast cell degranulation, we performed histamine (enzyme-linked immunosorbent assay) and β-hexosaminidase assays. To quantify interleukin (IL)-4, IL-5, and IL-13 levels in RBL-2H3 cells, we performed quantitative polymerase chain reaction (PCR); to quantify expression levels of IL-4 and IL-13 in HMC-1 cells, we used semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Finally, we detected the total and phosphorylated forms of extracellular signal-regulated kinase, p-38, and c-Jun N-terminal kinase proteins by immunoblotting. Results: BIOGF1K decreased the AD response by reducing both histamine and β-hexosaminidase release as well as reducing the secretion levels of IL-4, IL-5, and IL-13 in RBL-2H3 cells and IL-4 and IL-13 in HMC-1 cells. In addition, BIOGF1K decreased MAPK pathway activation in RBL-2H3 and HMC-1 cells. Conclusions: BIOGF1K attenuated the AD response, hence supporting its use as a promising and natural approach for treating AD.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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• pp.271-278
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• 2001

Oxidative stress and methylglyoxal (MG), a reactive dicarbonyl metabolites produced by enzymatic and non-enzymatic reaction of normal metabolism, induced aldose reductase (AR) expression in rat aortic smooth muscle cells (SMC). AR expression was induced in a time-dependent manner and reached at a maximum of 4.5-fold in 12 h of MG treatment. This effect of MG was completely abolished by cyclohemide and actinomycin D treatment suggesting AR was synthesized by de novo pathway. Pretreatment of the SMC with N-acetyl-L-cysteine significantly down-regulated the MG-induced AR mRNA. Furthermore, DL-Buthionine-(S,R)-sulfoximine, a reagent which depletes intracellular glutathione levels, increased the levels of MG-induced AR mRNA. These results indicated that MG induces AR mRNA by increasing the intracellular peroxide levels. Aminoguanidine, a scanvenger of dicarbonyl, significantly down-regulated the MG-induced AR mRNA. In addition, the inhibition of AR activities with statil, an AR inhibitor, enhanced the cytotoxic effect of MG on SMC under normal glucose, suggesting a protective role of AR against MG-induced cell damages. These results imply that the induction of AR by MG may contribute to an important cellular detoxification of reactive aldehyde compounds generated under oxidative stress in extrahepatic tissues.

• Bulletin of the Korean Chemical Society
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• v.14 no.5
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• pp.549-554
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• 1993

The CO substitution reactions in the complex, $Cp^*(C_5H_7)$CrCO with $PR_3(PR_3=PMePh_2,\;P(OCH_3)_3,\;PMe_2Ph)$ were investigated spectrophotometrically at various temperatures. For the reaction rates, it was suggested that the CO substitution reaction took place by first-order (dissociative) pathway. Activation parameters in decaline are ${\Delta}H^{\neq}= 21.99{\pm}2.4$ kcal/mol, ${\Delta}S^{\neq}= 8.9{\pm}7.1$ cal/mol·k. Unusually low value of ${\Delta}S^{\neq}$, suggested an ${\eta}^5-S{\to}\;{\eta}^5$-U conversion of the pentadienyl ligand. At various temperature, the rates of reaction for the Cp(pdl)CrCO complexes increase in the order $Cp^*(C_5H_7)$-CrCO < Cp$(C_5H_7)$CrCO < Cp(2,4-$C_5H_{11}$)CrCO, which can be attributed to the usual steric acceration or electronic influence for the ligand substitution of metal complexes. This suggestion was confirmed by the extended-Huckel molecular orbital (EHMO) calculations, which revealed that the energy of $[Cp^*(U-C_5H_7)Cr]^{\neq}$ transition state is about 4.93 kcal/mol lower than that of [Cp(S-$C_5H_7)Cr]^{\neq}$ transition state, and the arrangement of the overlap populations between Cr and the carbon of CO is $Cp^*(C_5H_7)$CrCO > Cp($C_5H_7$)CrCO > Cp(2,4-$C_7H_{11}$)CrCO.