• Journal of the Korean Chemical Society
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• v.30 no.2
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• pp.188-194
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• 1986

The rate constants for the solvolysis reactions of p-chlorobenzyl chloride in ethanol-water mixtures were determinded at 30${\circ}\;and\;40{\circ}$C up to 1,600bar. Rates of reaction were increased with increasing temperature and pressure, and decreased with increasing solvent composition of ethanol mole fraction. The plots of ln k against pressure are fitted to a second-order function in P, and values of ${\Delta}V^{\neq}\;and\;${\Delta}{\beta}^{\neq}$ are obtained. The values of ${\Delta}V^{\neq}\;and\;${\Delta}{\beta}^{\neq}$ extremum behavior at about 0.20 mole fraction of ethanol. This behavior is discussed in terms of solvent structure variation. From the relation between the plots of ln k versus the solvent parameter, q ≡ (D-1)/(2D+1), or the logarithmic molar water concentration, In $C_w$, it could be estimated that the reaction proceeds through $S_N1(2)$ mechanism.

• Journal of Life Science
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• v.23 no.8
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• pp.963-969
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• 2013

Although it is popularly believed that vitamin C protects cells from various genotoxicants, the degrees and mechanisms of itsprotective actions are not fully understood. In this study, vitamin C's protective effects against various genotoxicants were quantified, together with subsequent analyses on the mechanisms of these protective effects. Comet assay was employed to measure the degree of DNA damage in Chinese hamster ovary cells (CHO-K1) exposed to five genotoxicants, $H_2O_2$, $HgCl_2$, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), 4-nitroquinoline-1-oxide (4NQO), and UV-irradiation. In cases cells were treated with $H_2O_2$, $HgCl_2$, and 4NQO together with vitamin C, the damage to DNA decreased to the level of the control group. In cases of UV-irradiation, the protective effect of vitamin C appeared, but did not reach the control levels. Interestingly, vitamin C did not have protective effects against the genotoxicity of MNNG. The degrees of DNA damage of cells treated with vitamin C prior to exposure togenotoxicants were 28~49% lower than those of cells treated with vitamin C after being exposed to genotoxicants. In conclusion, vitamin C had strong antioxidanteffects against genotoxicants by being a primary antioxidant blocking genotoxicity reaching the cells, rather than being a secondary antioxidant acting on post-exposure DNA repair processes. However, vitamin C's protective effects appearto be limited, as there are genotoxicants, such as MNNG, whosegenotoxicityis not affected by vitamin C. Therefore, the results of this study warrant furtherstudies on toxic mechanisms of genotoxicants and their interactions with protective mechanisms of vitamin C.

• Transactions of the Korean Society of Mechanical Engineers B
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• v.32 no.8
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• pp.604-611
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• 2008

Detailed analysis of NO formation routes and its contributions with strain rate in hydrogen/air flames were numerically investigated. LiG detailed reaction mechanism has been used for calculation, which is compared with experimental data in literature. It shows good agreement with experiment for both temperature and NO mole fraction. Three routes have been found important for NO formation in hydrogen flames. These are the Thermal route, NNH route and $N_2O$ route. Strain rate were varied to discuss the $EI_{NO}$ reduction trend in hydrogen nonpremixed flames, which are analyzed by each NO formation routes. As a result, as the strain rate increase, $EI_{NO}$ decrease sharply until strain rate $100s^{-1}$ and decrease slowly until strain rate $310s^{-1}$ again, after that $EI_{NO}$ keeps nearly constant. It can be identified that $EI_{NO}$ trend with the strain rate is well explained by a combination of variation of production rate of above Thermal, NNH and $N_2O$ route. Also result of Thermal-Mech. that includes only thermal NO reaction is compared with those of Full-Mech. As a result, It can be identified that there was difference between the two results of calculation. It is attributed to result that Thermal-mech did not consider contributions of NNH and $N_2O$ route. From these result, we can conclude that NOx emission characteristics of hydrogen nonpremixed flames should consider contributions of above three routes simultaneously.

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1260-1266
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• 2009

Purpose : Idiopathic nephrotic syndrome (NS) can be clinically classified as steroid-sensitive and steroid-resistant. The detailed mechanism of glucocorticoid action in NS is currently unknown. Methods : In this study, we investigated 3 known single nucleotide polymorphisms (SNPs) (ER22/23EK, N363S, and BclI) of the glucocorticoid receptor gene (the NR3C1 gene) in 190 children with NS using polymerase chain reaction-restriction fragment length polymorphism and analyzed the correlation between the genotypes and clinicopathologic features of the patients. Results : Eighty patients (42.1%) were initial steroid nonresponders, of which 31 (16.3% of the total) developed end-stage renal disease during follow-up. Renal biopsy findings of 133 patients were available, of which 36 (31.9%) showed minimal changes in NS and 77 (68.1%) had focal segmental glomerulosclerosis. The distribution of the BclI genotypes was comparable between the patient and control groups, and the G allele frequencies in both the groups were almost the same. The ER22/23EK and N363S genotypes were homogenous as ER/ER and NN, respectively, in all the patients and in 100 control subjects. The BclI genotype showed no correlation with the NS onset age, initial steroid responsiveness, renal pathologic findings, or progression to end-stage renal disease. Conclusion : These data suggested that the ER22/23EK, N363S, and BclI SNPs in the NR3C1 gene do not affect the development of NS, initial steroid responsiveness, renal pathologic lesion, and progression to end-stage renal disease in Korean children with NS.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.584-589
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• 2001

Isopropryl 2-(1-3-dithiethane-2-ylidene)-2 [N-(4-methyl-thiazole-2-yl) carbamoyl] acetate (YH439) is currently under phase ll clinical trials by the Yuhan Research Center for use as a hepatoprotective agent. Unfortunately, the oral bioavailbility of YH439, which is sparingly soluble in water (i.e., $0.3{\;}\mu\textrm{g}/ml{\;}or{\;}0.91{$\mu}M$ at room temperature), reportedly, is negligibleregardless of the dose administered to rats in the 10-300 mg/kg range. The bioavailability of the compound increased up to 24%, when administered in the form of a micellar solution ($700{\;}\mu\textrm{g}/ml$or 2.1 mM for YH439) at a dose of 10 mg/kg, suggesting that its limited solubility is associated with its negligible bioavailability. In order to obtain additional informmation concerning the bioavailability of YH439, the mechanism(s) involved in gastrointestinal (Gl) absorption were investigated in the present study. For this purpose, the transport of YH430 across a Caco-2 cell monolayer was measured in a $Transwell^{\circledR}$. A permeability of $4.07{\times}10^{-5}{\;}cm/s$ was obtained for the absorptive (i.e., apical to basolateral direction) transport of $0.42{\mu}M$ YH439, implicating that the in vivo Cl absorption is nearly complete. The absorptive transport exhibited a slight concentration-dependency with an intrinsic clearance ($CL_{i}$) of $0.38{\mu}L/{\textrm{cm}^2}/sec$, which accounted for 28.1% of the total intrinsic clearance (i.e., $CL_i$ plus the intrinsic clearance for the linear component) of the transport. Thus, saturation of the absorption process appears to be a minor factor in limiting the bioavailability of the compound. The apparent permeability of YH439 from the basolateral to the apical direction (i.e., efflux, $6.67{\times}10^{-5}{\;}cm/s$) was comparable to that for absorptive transport, but, interestingly, a more distinct concentration-dependency was observed for this transport. However, the efflux does not appear to influence the bioavailability of the compound, as evidenced by the sufficiently high permeability in the absorption direction. Rather, a reportedly extensive first-pass hepatic metabolism appears to be a principal factor in limiting the bioavailability. In this respect, reducing the first-pass metabolism by some means would lead to a higher bioavailability of the compound. Thus, elevation of the absorption rate of YH439 becomes a necessity. From a practical point of view, increasing the concentration of YH439 in the Cl fluid appears to be a feasible way to increase the absorption rate, because the compound is primarily absorbed via a linear mechanism. In summary, the solubilization of YH439, as previously demonstrated for a micellar solution of the compound, appears to be a practical way to increase the oral bioavailability of YH439.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.370-378
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• 2009

N-myc downstream-regulated gene 2 (NDRG2) has recently been found to be a tumor suppressor gene. Although it has been reported that NDRG2 expression in breast cancer cells decreases cell proliferation by inhibiting STAT3 activation via SOCS1 induction, the molecular mechanism of chemotherapeutic agent-induced apoptosis is not well known. To elucidate the effect of NDRG2 on the apoptotic pathway induced by doxorubicin, we established stable cell lines expressing NDRG2 and investigated the effect of NDRG2 expression on the doxorubicin-induced apoptosis. While STAT3 activation was remarkably inhibited by NDRG2 overexpression, the expression level of p21 was increased by NDRG2 expression. We confirmed that NDRG2-expressing cells treated with doxorubicin suppressed STAT3 activation and upregulated p21 expression. NDRG2 expression considerably enhanced TUNEL positive apoptotic cells, poly-ADP ribose polymerase (PARP) cleavage, release of cytochrome c to cytosol, and caspase-3 activity in doxorubicin-induced apoptosis. Bid expression in a resting state and after treatment with doxorubicin increased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells. Meanwhile, Bcl-$x_L$ expression decreased in MDA-MB-231-NDRG2 cells compared to MDA-MB-231-mock cells in a resting state and in doxorubicin-treated cells. Collectively, these data suggest that suppression of STAT3 activation by NDRG2 influences the sensitivity to doxorubicin-induced apoptosis of breast cancer cells and this may provide a potential therapeutic benefit to overcome the resistance against doxorubicin in breast cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.479-499
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• 2022

The lack of a clonal renin-secreting cell line has greatly hindered the investigation of the regulatory mechanisms of renin secretion at the cellular, biochemical, and molecular levels. In the present study, we investigated whether it was possible to induce phenotypic switching of the renin-expressing clonal cell line As4.1 from constitutive inactive renin secretion to regulated active renin secretion. When grown to postconfluence for at least two days in media containing fetal bovine serum or insulin-like growth factor-1, the formation of cell-cell contacts via N-cadherin triggered downstream cellular signaling cascades and activated smooth muscle-specific genes, culminating in phenotypic switching to a regulated active renin secretion phenotype, including responding to the key stimuli of active renin secretion. With the use of phenotype-switched As4.1 cells, we provide the first evidence that active renin secretion via exocytosis is regulated by phosphorylation/dephosphorylation of the 20 kDa myosin light chain. The molecular mechanism of phenotypic switching in As4.1 cells described here could serve as a working model for full phenotypic modulation of other secretory cell lines with incomplete phenotypes.

• Bulletin of the Korean Chemical Society
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• v.33 no.3
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• pp.775-778
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• 2012

The potential energy surfaces of ammonia molecule adsorptions on the symmetrically chlorinated Si(100)-$2{\times}1$ surface were explored with SIMOMM:MP2/6-31G(d). It was found that the initial nucleophilic attack by ammonia nitrogen to the surface Si forms a $S_N2$ type transition state, which eventually leads to an HCl molecular desorption. The second ammonia molecule adsorption requires much less reaction barrier, which can be rationalized by the surface cooperative effect. In general, it was shown that the surface Si-Cl bonds can be easily subjected to the substitution reactions by ammonia molecules yielding symmetric surface Si-$NH_2$ bonds, which can be a good initial template for subsequent surface chemical modifications. The ammonia adsorptions are in general more facile than the corresponding water adsorption, since ammonia is better nucleophile.

• Proceedings of the Korean Institute of Surface Engineering Conference
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• 2009.05a
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• pp.202-203
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• 2009

Plasma etching was studied to obtain high-efficiency Si solar cells. SiN nanoparticles were observed upon the plasma treatment using SF6 gas. The mechanism of the nanoparticles formation has been studied. A net increase in the current density (Jsc) of the cells of $1.7mA/cm^2$ and in the conversion efficiency ($\eta$) of 2.1% is obtained after the plasma treatment for 10s, thanks to the significant decrease of reflection in the shorter wavelength range.

• BMB Reports
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• v.51 no.8
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• pp.388-393
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• 2018

The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP [Basic Leucine Zipper]) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a functional positive cellular factor in HIV-1 production. To determine the mechanism by which ATF4 regulates the HIV-1 life cycle, we assessed the effect of the overexpression of wild type ATF4 and its various derivatives on HIV-1 LTR-mediated transcriptional activation and the production of HIV-1 particles. This effect was studied through co-transfection experiments with either reporter vectors or proviral DNA. We found that the N-terminal domains of ATF4 are involved in HIV-1 LTR-mediated transcriptional activation, and thus in HIV-1 production.