• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.262-262
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• 1994

Ras oncogene의 산물로서 대부분의 암조직이나 transformed human cell에서 거의 공통적으로 발견되는 p21 단백질은 C-terminal processing에 의해 먼저 C-terminal cysyeine에 palmition 된 후 carboxylmethylation 된다. Palmitation은 transforming activity의 요건인 세포막에 대한 친화력을 유지시키기 위한것으로 추측되며, cysteine residue의 carboxylmethylation의 의미는 아직 확실히 밝혀지고 있지 않으나 세포막에 대한 친화력을 증가 시키는 것으로 추측되고있다. 본 연구에서는 S-Farnesylcysteine Methyltransferase의 기질로서 N-acetyl-S-trans, trans-farnesyl-L-cysteine(AFC)을 합성하였으며, 본 실험실에서 계속 연구하여 온 돼지 간장으로 부터 정제한 천연 단백성 Methylation Inhibitor의 S-Farnesylcysteine Methyltransferase 활성에 대한 억제효과를 검색하였다. 천연 단백성 Methylation Inhibitor는 돼지 간조직의 soluble fraction을 열처리하여 Sephadex G-25 column chromatngraphy한 후 reverse phase HPLC로 정제하였다. 본 inhibitor는 약 10개의 아미노산으로 구성된 peptide성 천연물질로 분자량은 1,400 Da 으로서 합성한 AFC를 기질로 하였을 때, 흰쥐 뇌 조직내 S-Farnesylcysteine methyltransferase에 대한 $IC_{50}$/은 0,82 $\times$ $10^{-6}$ M이었으며 또한 human cancer cell line의 S-Farnesylcysteine Methyltransferase에 대해서도 현저한 저해효과를 나타내었다.

• Preventive Nutrition and Food Science
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• v.19 no.4
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• pp.268-273
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• 2014

The induction of detoxification enzymes by benzyl isothiocyanate (BITC) and its synthetic N-acetyl-L-cysteine (NAC) conjugate (NAC-BITC) was examined in Hepa1c1c7 murine hepatoma cells. BITC and NAC-BITC inhibited Hepa1c1c7 cell growth in a dose-dependent manner. Cell growth was 4.5~57.2% lower in Hepa1c1c7 cells treated with $0.1{\sim}1.0{\mu}M$ BITC than in control-treated Hepa1c1c7 cells. The NAC-BITC treatment had a similar inhibitory pattern on Hepa1c1c7 cell growth; $0.5{\mu}M$ and $10{\mu}M$ NAC-BITC decreased cell growth by 13.6% and 47.4%, respectively. Treatment of Hepa1c1c7 cells with $0.1{\sim}2.0{\mu}M$ BITC also elicited a dose-response effect on the induction of quinone reductase quinone reductase (QR) activity and QR mRNA expression. Treatment with $1{\mu}M$ and $2{\mu}M$ BITC caused 1.8- and 2.8-fold inductions of QR mRNA, respectively. By comparison, treatment with $1{\mu}M$ and $2{\mu}M$ NAC-BITC caused 1.6-and 1.9-fold inductions of QR mRNA, respectively. Cytochrome P450 (CYP) 1A1 and CYP2E1 induction were lower in $0.1{\sim}2{\mu}M$ BITC-treated cells than in control-treated cells. CYP2E1 activity was 1.2-fold greater in $0.1{\mu}M$ NAC-BITC-treated cells than in control-treated cells. However, the CYP2E1 activity of cells treated with higher concentrations (i.e., $1{\sim}2{\mu}M$) of NAC-BITC was similar to the activity of control-treated cells. Considering the potential of isothiocyanatesto prevent cancer, these results provide support for the use of BITC and NAC-BITC conjugates as chemopreventive agents.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.545-553
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• 2003

The expression of cyclooxygenase-2 (COX-2) is a characteristic response to inflammation, which can be inhibited with sodium salicylate. IL-1$\beta$ and TNF-$\alpha$ can induce extracellular signal-regulated kinase (ERK), IKK, IkB degradation and NF-$\kappa$B activation. Salicylate inhibited the IL-1$\beta$ and TNF-$\alpha$-induced COX-2 expressions, regulated the activation of ERK, IKK and IkB degradation, and the subsequent activation of NF-$\kappa$B, in neonatal rat ventricular cardiomyocytes. The inhibition of the ERK pathway, with a selective inhibitor, PD098059, blocked the expressions of IL-1$\beta$ and TNF-$\alpha$-induced COX-2 and $PGE_2$ release. The antioxidant, N-acetyl-cysteine, also reduced the glutathione or catalase- attenuated COX-2 expressions in IL-1$\beta$ and TNF-$\alpha$-treated cells. This antioxidant also inhibited the activation of ERK and NF-$\kappa$B in neonatal rat cardiomyocytes. In addition, IL-1$\beta$ and TNF-$\alpha$-stimulated the release of reactive oxygen species (ROS) in the cardiomyocytes. However, salicylate had no inhibitory effect on the release of ROS in the DCFDA assay. The results showed that salicylate inhibited the activation of ERK and IKK, I$\kappa$B degradation and NF-$\kappa$B activation, independently of the release of ROS, which suggested that salicylate exerts its anti-inflammatory action through the inhibition of ERK, IKK, IkB and NF-$\kappa$B, and the resultant COX-2 expression pathway in neonatal rat ventricular cardiomyocytes.

• Archives of Pharmacal Research
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• v.17 no.5
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• pp.354-359
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• 1994

The activity of SD-framesylcysteine O-methyltransferase was assayed by incubating the enzyrne with a synthetic in vitro substrate, [N-acetyl-S-trans, trns-famesyl-L-cysteine (AFC)], together with S-adenosyl-L-[emthyl-$_{14}$C)ester(AFCME)], was then analyzed either directly on HPLC or by converting the AFC[$methyl^{14}C$]ME to [$methyl^{14}C$] aclcohol by basehydrolysis. Employing these two analytical methods, it was established that a peptide purifed from rat liver cytosol fraction [Int. J. Biochem., 25, 1157 919930] strongly inhibited the above enzyme activity with $IC_{50}\; of\; 7.1\times 10^{-8}$ M. Also, the S-famesylcysteine O-methyltransferase from several human colon cancer cells was equally inhibited by the peptide.

• Bulletin of the Korean Chemical Society
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• v.26 no.8
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• pp.1255-1259
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• 2005

Lewy bodies (LBs) are neuronal inclusions that are closely related to Parkinson's disease (PD). The filamentous component of LB from patients with PD contains biochemically altered $\alpha$-synuclein. We have investigated the effect of the oxidized products of catecholamines on the modification of $\alpha$-synuclein. When $\alpha$-synuclein was incubated with the oxidized 3,4-dihydroxyphenylalanine (L-DOPA) or dopamine, the protein was induced to be aggregated. The oxidized catecholamine-mediated $\alpha$-synuclein aggregation was enhanced by copper ion. Radical scavengers, azide and N-acetyl cysteine significantly prevented the oxidized catecholamine-mediated $\alpha$-synuclein aggregation. The results suggest that free radical may play a role in $\alpha$-synuclein aggregation. Exposure of $\alpha$-synuclein to the oxidized products of catecholamines led to the formation of dityrosine. Antioxidant dipeptides carnosine, homocarnosine and anserine significantly protected $\alpha$-synuclein from the aggregation induced by the oxidized products of catecholamines.

• Korean Journal of Environmental Biology
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• v.39 no.3
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• pp.354-361
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• 2021

Understanding the phytotoxic mechanism of methyl bromide (MB), an essential fumigant during the quarantine and pre-shipment process, is urgently needed to ensure its proper use and reduce international economic losses. In a previous study, two main MB-induced toxic mechanisms such as reactive oxygen species (ROS) and auxin distribution were selected by analyzing transcriptomic analysis. In the study, a 3-week-old A. thaliana was supplied with 1 mM ROS scavengers [N-acetyl-L-cysteine (NAC) or L-glutathione (GSH)] and 1µM indole-3-acetic acid(IAA) three times every 12 h, and visual and gene expression assessments were performed to evaluate the reduction in phytotoxicity by supplements. Phytotoxic effects on the MB-4h exposed group were decreased with GSH application compared to the other single supplements and a combination of supplements at 7 days post fumigation. Among these supplements, GSH at a concentration of 1, 2, and 5mM was suppled to A. thaliana with MB-fumigation. During a long-term observation of 2 weeks after the fumigation, 5 mM GSH application was the most effective in minimizing MB-induced phytotoxic effects with up-regulation of HSP70 expression and increase in main stem length. These results indicated that ROS was a main key factor of MB-induced phytotoxicity and that GSH can be used as a supplement to reduce the phytotoxicity of MB.

• Journal of Photoscience
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• v.9 no.2
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• pp.201-204
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• 2002

Epidermal cells produce a panel of antioxidants as well as cytokines after UVB irradiation, which counteract reactive oxygen species, however, how these antioxidants might regulate melanogenesis is unclear. An important constituent of the cellular antioxidant buffering system which controls the redox state of proteins is thioredoxin (TRX), a 13-kD protein that catalyzes thiol-disulfide exchange reactions, regulates activation of transcription factors, and possesses several other biological functions similar to cytokines. TRX suppressed the UVB-induced production and secretion of $\alpha$-melanocyte stimulating hormone ($\alpha$-MSH) and of adrenocorticotropic hormone (ACTH), and also suppressed proopiomelanocortin (POMC) mRNA expression by normal human keratinocyte (KC)s. Further, L-cysteine, N-acetyl-cysteine, $\alpha$-tocopheryl ferulate showed suppressive effect on UVB-induced POMC mRNA expression. However, TRX released from UVB-irradiated KCs stimulated melanogenesis by up-regulating MSH receptor expression and its binding activity in melanocyte (MC)s. UVB-induced KC derived cytokines such as IL1, IL6, and ET1 upregulated MSH-receptor binding ability as well as MCl-R mRNA expression in cultured normal human MCs. MCl-R has a tendency to be upregulated by UVB-induced KC-derived cytokines as well as by direct UVB irradiation. These results suggest that antioxidants such as TRX suppresses UVB induction of POMC, but in the case of MCl-R, this gene can be mainly in the trend of upregulation by UVB-induced KC-derived factors including TRX.

• Archives of Pharmacal Research
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• v.24 no.5
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• pp.418-423
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• 2001

CC-MS analysis on the essential oil (CC-oil) of Cinnamomum cassia stem bark led to the identification of cinnamaldehyde (CNA, 1), 2-hydroxycinnamaldehyde (2-CNA), coumarin (2), and cinnamyl acetate. The major volatile flavor in CC-oil was found to be 2-CNA. Coumarin was first isolated from this plant by photochemical isolation and spectroscopic analysis. CNA and CC-oil showed potent cytotoxicity, which was effectively prevented by N-acetyl-L-cysteine (NAC) treatment. Intraperitoneal administration with CNA considerably decreased malondialdehyde (MDA) formation and glutathione S-transferase activity in rats. These results suggest that CC-oil and CNA can regulate the triggering of hepatic drugmetabolizing enzymes by the formation of a glutathione-conjugate.

• Natural Product Sciences
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• v.12 no.2
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• pp.94-100
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• 2006

The essential oil (EC-oil) obtained from the buds of Eugenia caryophyllata (Myrtaceae) was examined for its free radical-scavenging activity, cytotoxicity, and in vivo toxicity. To find the xenobiotic properties of EC-oil, serum thiobarbituric acid reactive substances (TBARS) level and hepatic drug-metabolizing enzyme activities were measured. It was found that EC-oil displayed xenobiotic properties like bromobenzene. The cytotoxicities of eugenol and of the EC-oil were greatly attenuated by the sulfhydryl-containing N-acetyl-L-cysteine (NAC), suggesting that eugenol was susceptible to nucleophilic sulfhydryl. In addition, eugenol also showed potent free radical-scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Moreover, methyleugenol considerably exhibited less cytotoxicity and less potent free radical-scavenging activity than eugenol, and the cell viability of the methyleugenol was more increased with NAC treatment than the eugenol. These results indicate that the phenolic OH in eugenol may play a crucial role in both cytotoxicity and free radical-scavenging activity. The fashion on oxidative stress and hepatic drug-metabolizing enzyme activities of eugenol resembled those of bromobenznene.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.1
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• pp.47-54
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• 2000

Transition metal ions including $Se^{2+},\;Cd^{2+},\;Hg^{2+}\;or\;Mn^{2+}$ have been thought to disturb the bone metabolism directly. However, the mechanism for the bone lesion is unknown. In this study, we demonstrated that MC3T3E1 osteoblasts, exposed to various transition metal ions; selenium, cadmium, mercury or manganese, generated massive amounts of reactive oxygen species (ROS). The released ROS were completely quenched by free radical scavengers-N-acetyl cysteine (NAC), reduced glutathione (GSH), or superoxide dismutase (SOD). First, we have observed that selenium $(10\;{\mu}M),$ cadmium $(100\;{\mu}M),$ mercury $(100\;{\mu}M)$ or manganese (1 mM) treatment induced apoptotic phenomena like DNA fragmentation, chromatin condensation and caspase-3-like cysteine protease activation in MC3T3E1 osteoblasts. Concomitant treatment of antioxidant; N-acetyl-L-cysteine (NAC), reduced-form glutathione (GSH), or superoxide dismutase (SOD), prevented apoptosis induced by each of the transition metal ions. Catalase or dimethylsulfoxide (DMSO) has less potent inhibitory effect on the apoptosis, compared with NAC, GSH or SOD. In line with the results, nitroblue tetrazolium (NBT) stain shows that each of the transition metals is a potent source of free radicals in MC3T3E1 osteoblast. Our data show that oxidative damage is associated with the induction of apoptosis in MC3T3E1 osteoblasts following $Se^{2+},\;Cd^{2+},\;Hg^{2+}\;or\;Mn^{2+}$ treatment.