• Archives of Pharmacal Research
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• v.9 no.2
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• pp.99-110
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• 1986

In order to use for metabolic studies of tranylcypromine (TCP), TCP-phenyl-$d_{5}$ was synthesized via the intermediates, 3-benzoylpropionic acid-$d_{5}$ and trans-2-phenylcyclopropanecarboxylic acid-$d_{5}$ -TCP(0.22 mmole/kg) and its deuterated analog were administered s. c. to the rats and GC/MS analyses of the urines led to the detection of N-acetyltranylcypromine (ATCP) and glucuronide conjugate of phenyl-hydroxylated ATCP. MAO activities in rat brain were measured using serotonin as the substrate. In vitro $IC_{50}$ of ATCP was determined to be $10^{-3}M$. The inhibitions by ATCP were not dependent on the preincubation time and were reversed by washing sedimented mitochondrial pellets after the preincubation. In vivo MAO inhibitions at various times of 0.5, 1.5, 3, 6, 12, and 23 hr after the administration of 0.4 mmole/kg (i. p. ) of ATCP were found to be 0.13, 73, 90, 89, and 74 %, respectively. Similarly, the inhibition percents by 0.015 mmole/kg (i. p. ) of TCP were 94, 99, 95, 91, 71 and 49%. The results strongly suggest that deacetylated product of ATCP may account for its in vivo MAO inhibition. The relationship between the metabolism via phenyl-hydroxylation and the in vivo potency of TCP was examined by QSAR study and it was found that groupings discriminating between the compounds with p-substituents and those without them only ensure high correlations, suggesting that ring-hydroxylation which occurs at the para position in most of the compounds is a determining factor to the potency of TCP.

• Journal of Microbiology and Biotechnology
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• v.19 no.5
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• pp.447-454
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• 2009

The transport of spermidine into a cyanobacterium, Synechocystis sp. pec 6803, was characterized by measuring the uptake of $^{14}C$-spermidine. Spermidine transport was shown to be saturable with an apparent affinity constant ($K_m$) value of $67{\mu}M$ and a maximal velocity ($V_{max}$) value of 0.45 nmol/min/mg protein. Spermidine uptake was pH-dependent with the pH optimum being 8.0. The competition experiment showed strong inhibition of spermidine uptake by putrescine and spermine, whereas amino acids were hardly inhibitory. The inhibition kinetics of spermidine transport by putrescine and spermine was found to be noncompetitive with $K_i$ values of 292 and $432{\mu}M$, respectively. The inhibition of spermidine transport by various metabolic inhibitors and ionophores suggests that spermidine uptake is energy-dependent. The diminution of cell growth was observed in cells grown at a high concentration of NaCl. Addition of a low concentration of spermidine at 0.5 mM relieved growth inhibition by salt stress. Upshift of the external osmolality generated by either NaCl or sorbitol caused an increased spermidine transport with about 30-40% increase at 10 mosmol/kg upshift.

• Archives of Pharmacal Research
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• v.14 no.4
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• pp.330-335
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• 1991

The effects of physostigmine and neostigmine on the parathin induced toxicity were examined in adult female rats. Physostigmine $(100\;{\mu}g/kg,\;ip)$ or neostigmine $(200\;{\mu}g/kg,\;ip)$ inhibited acetylcholinesterase (AChE) and cholinesterase (ChE) activities in blood, brain and lung when the enzyme activity was measured 30 min after the treatment. At the doses of two carbamates equipotent on brain AChE, neostigmine showed greater inhibition on peripheral AChE/ChE. The enzyme activity returned to normal in 120 min following the carbamates except in the lung of rats treated with neostigmine. Carbamates administered 30 min prior to parathion (2 mg/kg) antagonized the inhibition of AChE/ChE by parathion when the enzyme activity was measured 2 hr following parathion. Neostigmine showed greater protective effect on peripheral AChE/ChE. The effect of either carbamate on AChE/ChE was not significant 2 hr beyond the parathion treatment. Carbamates decreased the mortality of rats challenged with a lethal dose of parathion (4 mg/kg, ip) either when treated alone or in combination with atropine (10 mg/kg, ip). Lethal action of paraoxon (1.5 mg/ks ip), the active metabolite of parathion was also decreased by the carbamate treatment indicating that the protection was not mediated by competitive inhibition of metabolic conversion of parathion to paraoxon. The results suggest that carbamylation of the active sites may not be the sole underlying mechanism of protection provided by the carbamates.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.6
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• pp.328-333
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• 2017

Desomodii Herba (DH) has been shown to exhibit pharmacologyical activities, such as increase myocaridal contraction and secretion of hepatic bile. DH is used to reduce pain caused by rheumatoid arthritis(RA) in Korean medicine. However, the DH exact(DHE) effect and mechanism on rheumatoid arthritis are unknown. In this study, we aimed at the inhibitory effect of DHE on rheumatoid arthritis, and investigated the effect in collagen-induced mice arthritis model and TNF-${\alpha}$ induced MMP-1 and MMP-3 expression including the molecular basis in rheumatoid arthritis synovial fibroblasts (RASFs).The effect of DHE on RA was measured by clinical scoring system. In RASFs, expression of MMP-1 and MMP-3 was assessed by Western blotting and real-time PCR. Also, Western blotting used to evaluate the phosphorylation levels of p38, ERK and JNK and activation of NF-${\kappa}B$ and AP-1. Our results showed that DHE reduced collagen-induced arthritis in mice. DHE inhibits TNF-${\alpha}$ induced MMP-1 and MMP-3 expression and mRNA levels in RASFs. The inhibitory effect of DHE was mediated by the inhibition of the AP-1/JNK signaling pathway. Taken together, our results suggest that the DHE may have preventive potential for rheumatoid arthritis.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 1996.12a
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• pp.63-63
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• 1996

We performed chromosomal aberration assay in Chinese Hamster Lung (CHL) cells in vitro to evaluate theclastogenicity of 11 synthetic chemicals which were listed in Toxicity Evaluation Program of Ministry of Environment of Republic of Korea in 1996. All of the chemicals were carried out MTT assay to determine the 50% cell growth inhibition concentration. All compounds were tested with and without metabolic activation system. Benzoyl chloride revealed positive result at $43\;\mu\textrm{g}/m{\ell}$ in the presence of metabolic activation system, and at 30.8, 61.5 and $123\;\mu\textrm{g}/m{\ell}$ in the absence of metabolic activation system. And p-phenoxy ethanol was observed as positive with the metabolic activation system, but negative without metabolic activation system. Especially 2-propyn-l-ol showed high frequency of pulverization and showed critical difference of cytotoxicity between with and without S9 mixture. Pulverizatiuon is not included in the frequency of structural aberration in our criteria. Dicyclopentadiene, methacrylic acid, aa-dimethylbenzyl hydroperoxide, benzylbutyl phthalate, and p-chlorophenal were revealed negative results.esults.

• The Korean Journal of Pesticide Science
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• v.2 no.3
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• pp.1-20
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• 1998

Chlorsulfuron, one of sulfonylurea herbicides acts through inhibition of acetolactate syuthase (EC 4.1.3.18; ALS, also known as acetohydroxyacid synthase) in the branched-chain amino acid biosynthesis process. After chlorsulfuron-ALS interaction, many physiological and metabolic disruptions occur in plants. However, it is not clear how this chlorsulfuron-ALS interaction affects those physiological and metabolic processes and how this interaction leads subsequently to plant death. Several researchers suggested that the death of chlorsulfuron-treated plants might be due to a shortage of the branched-chain amino acids, an accumulation of toxic metabolites, and/or a depletion of photoassimilates. It remains as a mystery presently, however, if such changes result in the plant death. In this review, we discussed how the chlorsulfuran-ALS interaction leads to physiological and metabolic disruptions in plants.

• Journal of Microbiology and Biotechnology
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• v.6 no.6
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• pp.425-431
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• 1996

The enzymatic characteristics of Alcaligenes latus were investigated by measuring the variations of various enzyme activities related to biosynthesis and degradation of poly-${\beta}$-hydroxybutyrate (PHB) during cultivation. All PHB biosynthetic enzymes, ${\beta}$-ketothiolase, acetoacetyl-CoA reductase, and PHB synthase, were activated gradually at the PHB accumulation stage, and the PHB synthase showed the highest value among three enzymes. This indicates that the rate of PHB biosynthesis is mainly controlled by either ${\beta}$-ketothiolase or acetoacetyl-CoA reductase rather than PHB synthase. The enzymatic activities related to the degradation of PHB were also measured, and the degradation of PHB was controlled by the activity of PHB depolymerase. The effect of supplements of metabolic regulators, citrate and tyrosine, was also investigated, and the activity of glucose-6-phosphate dehydrogenase was increased by metabolic regulators, especially by tyrosine. The activities of ${\beta}$-ketothiolase and acetoacetyl-CoA reductase were also activated by citrate and tyrosine, while the activity of PHB depolymerase was depressed. The increased rate and yield of PHB biosynthesis by metabolic regulators may be due to the increment of acetyl-CoA concentration either by the repression of the TCA cycle by citrate through product inhibition or by the activation of sucrose metabolism by the supplemented tyrosine.

• Journal of Microbiology and Biotechnology
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• v.28 no.5
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• pp.784-795
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• 2018

Bacillus amyloliquefaciens Pc3 was isolated from Antarctic seawater with antifungal activity. In order to investigate the metabolic regulation mechanism in the biosynthesis of lipopeptides in B. amyloliquefaciens Pc3, GC/MS-based metabolomics was used when exogenous indole was added. The intracellular metabolite profiles showed decreased asparagine, aspartic acid, glutamine, glutamic acid, threonine, valine, isoleucine, hexadecanoic acid, and octadecanoic acid in the indole-treated groups, which were involved in the biosynthesis of lipopeptides. B. amyloliquefaciens Pc3 exhibited a growth promotion, bacterial total protein increase, and lipopeptide biosynthesis inhibition upon the addition of indole. Besides this, real-time PCR analysis further revealed that the transcription of lipopeptide biosynthesis genes ituD, fenA, and srfA-A were downregulated by indole with 22.4-, 21.98-, and 26.0-fold, respectively. It therefore was speculated that as the metabolic flux of most of the amino acids and fatty acids were transferred to the synthesis of proteins and biomass, lipopeptide biosynthesis was weakened owing to the lack of precursor amino acids and fatty acids.

• Journal of the Korean Magnetic Resonance Society
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• v.18 no.1
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• pp.10-14
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• 2014

Hsp90 is a good drug target molecule that is involved in regulating various signaling pathway in normal cell and the role of Hsp90 is highly emphasized especially in cancer cells. Thus, much efforts for discovery and development of Hsp90 inhibitor have been continued and a few Hsp90 inhibitors targeting the N-terminal ATP binding site are being tested in the clinical trials. There are no metabolic signature molecules that can be used to evaluate the effect of Hsp90 inhibition. We previously found a potential C-domain binder named PPC1 that is a synthetic small molecule. Here we report the metabolomics study to find signature metabolites upon treatment of PPC1 compound in lung cancer cell line, A549 and discuss the potentiality of metabolomic approach for evaluation of hit compounds.

• Molecules and Cells
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• v.41 no.1
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• pp.3-10
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• 2018

Autophagy is one of the major degradative mechanisms that can eliminate excessive nutrients, toxic protein aggregates, damaged organelles and invading microorganisms. In response to obesity and obesity-associated lipotoxic, proteotoxic and oxidative stresses, autophagy plays an essential role in maintaining physiological homeostasis. However, obesity and its associated stress insults can often interfere with the autophagic process through various mechanisms, which result in further aggravation of obesity-related metabolic pathologies in multiple metabolic organs. Paradoxically, inhibition of autophagy, within specific contexts, indirectly produces beneficial effects that can alleviate several detrimental consequences of obesity. In this minireview, we will provide a brief discussion about our current understanding of the impact of obesity on autophagy and the role of autophagy dysregulation in modulating obesity-associated pathological outcomes.