한국인 집단에서 Cytochrome P450 1A1 의 유전적 다형성

정혜광,구희경,정태천 한국유전학회 1997 Genes & Genomics Vol.19 No.2

We have quantified genotype frequency of the cytochrome P450 (P450) 1A1, which is primarily responsible for the metabolic activation of carcinogenic polycyclic aromatic hydrocarbones, in Korean population by PCR and RFLP at two sites associated with lung cancer; Mspl RFLP in the 3' flanking region of the gene and Ncol RFLP in exon 7 (a point mutation of isoleucine to valine substitution) near the catalytic region of the enzyme. The genotype frequencies of homozygous wild type (Mspl site-absent), heterozygous mutant type (Mspl site-present), and homozygous mutant type in Mspl RFLP were 0.45, 0.42, and 0.13, respectively. The genotype frequencies of homozygous wild type (Ile/ Ile) and heterozygous mutant type (lle/Val) in Ncol RFLP were 0.54 and 0.46, respectively. The homozygous mutant type (Val/Val) in Ncol RFLP was not observed in Korean population.

생약추출물의 Cytochrome P450 약물대사 효소계 저해활성

정혜광,유호진,장영수,박성준,문영희,우은란 한국생약학회 2002 생약학회지 Vol.33 No.1

인슐린저항성 HepG2 세포에서 phillyrin의 포도당신생합성 개선효과

정혜광,이승연,이기호,김미연,채주연,김재원 한국생약학회 2022 생약학회지 Vol.53 No.3

Type II diabetes mellitus (T2DM) is a chronic metabolic disease caused by insulin resistance, and abnormally elevated hepatic gluconeogenesis is characterized. Phillyrin, one of the major active constituents of Forsythia suspense, is known to possess the anti-inflammatory and anti-oxidant effects. However, the anti-diabetes mellitus effect of phillyrin and its molecular mechanisms are unclear. The aim of the current study was to investigate the role of phillyrin on gluconeogenesis in insulin resistant HepG2 cells. Phillyrin suppressed high glucose (HG)-induced glucose production. In addition, phillyrin reduced HG-induced the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), major genes in hepatic gluconeogenesis. Phillyrin treatment attenuated HG-induced nucleus protein levels of FOXO1 and HDAC5 and increased the phosphorylation of Akt, AMPK, HDAC5, and FOXO1. The block of AMPK and Akt activity did not exert the inhibitory effect of phillyrin on gluconeogenesis in insulin resistant HepG2. Taken together, these results suggest that phillyrin inhibits gluconeogenesis of hepatocytes to improve glucose metabolism, through the regulation of LKB1/AMPK/HDAC5 and PI3K/AKT/FOXO1 pathway. These results indicate that phillyrin may be useful in improving hepatic gluconeogenesis associated with insulin resistant and T2DM.

메탈로티오네인의 기능

정혜광,김시욱,고문주 조선대학교 생명과학연구소 1998 생명과학 연구 Vol.6 No.-

For four decades after the original discovery of the small protein, metallothionein, its functional significance remains unclear. It is generally accepted that the principal roles of metallothioneins are detoxification of heavy metals and regulation of metabolism of essential trace metals. Nowadays there are emerging accounts on the function of metallothionein as an antioxidant. This manuscript reviews the structure, functions and induction of metallothioneins, especially focuses on the function as antioxidant. The medical implications of the free radical scavenging properties of metallothioneins are also discussed.

한국인 집단에서 Cytochrome P450 2E1의 유전적 다형성 ( Genetic Polymorphism of Cytochrome P450 2E1 in Korean Population )

정혜광,구희경,이상섭,양규환,정태천,변부형 한국환경성돌연변이발암원학회 1996 한국환경성돌연변이·발암원학회지 Vol.16 No.2

Structure-activity Relationships of 4-Senecioyloxymethyl-6,7-dimethoxycoumarin Analogues as Anti-Allergic Agents

정혜광,김동희,Mirim Jin,Praveen Kumar Siripuram,최용석,송규용,Jee Hyun Lee,Sang Hun Jung,Eun Hee Han,Joo Hwan Kim 대한화학회 2007 Bulletin of the Korean Chemical Society Vol.28 No.10

Mast cells are key effector cells in the early phase allergic inflammation and in diverse immunological and pathological processes. In order to understand the effect on reduction of the anti-dinitrophenyl (DNP) IgE antibody-induced b-hexosaminidase release in RBL-2H3 rat mast cells, a novel series of 4-senecioyloxy- methyl-6,7-dimethoxycoumarins (SMDC) was prepared by reacting 4-chloromethyl-6,7-dimethoxycoumarin with various carboxylic acids. Compounds 8-11 with cyclic moiety such as phenyl, thiophenyl, pyridinyl, and furanyl group were found to inhibit-hexosaminidase release more potently (5.98-9.62 mM) than compounds 3-7 and 12 with acyclic moiety (19.32-76.78 mM). Furthermore, compounds 8 and 9 inhibited IgE-induced ear swelling and significantly reduced systemic passive cutaneous anaphylaxis reaction in mice.

Anti-tumor effects of metformin: Effects of metformin on Sirt1, Nrf2 and AhR expression in cancer cells

정혜광 ( Hye Gwang Jeong ) 전남대학교 약품개발연구소 2016 약품개발연구지 Vol.25 No.-

The expression of Sirt1, Nrf2 and AhR relates to tumorigenesis, chemoresistance and carcinogenesis. Accumulating evidence suggests that metformin has antitumor activity. This study investigated effects of metformin on expression of Sirt1, Nrf2, AhR and its downstream target genes in cancer cells. Results indicated that metformin down-regulated the constitutive and inducible expression of CYP1A1 and CYP1B1 in MCF-7 and MDA-MB-231 breast cancer cells. Down-regulation of AhR expression was required for metformin-mediated decreases in CYP1A1 and CYP1B1 expression. Metformin inhibited endogenous AhR ligand-induced CYP1A1 and CYP1B1 expression by suppressing TDO expression. Moreover, metformin strongly suppresses HO-1 expression in A549 cancer cells. Metformin also markedly reduced Nrf2 activation and expression. The regulation of Nrf2 expression by metformin is mediated through a Keap1-independent mechanism and that the reduction. of Nrf2 expression is mediated by an attenuation of Raf-ERK signaling by metformin. Additionally, metformin induced p53 protein levels in wild-type p53 cancer cells resulted in up-regulation of miR-34a and down-regulation of Sirt1. Genetic tools demonstrated that the reduction of Sirt1 and Pgc-1α by metformin caused Nrf2 down-regulation via suppression of PPARγ transcriptional activity. The Sirt1 reduction by metformin increased DR5 expression. Metformin pretreatment enhanced the susceptibility of cancer cells to oxidative stress and TRAIL-induced apoptosis. These results demonstrated that metformin down-regulates Sirt1, Nrf2 and AhR expression in cancer cells following with correlative pharmacological activities. Metformin is commonly used for type 2 diabetes. Therefore, metformin may be an effective therapy for the cancer prevention and treatment.

Capsaicin으I PDGF-BB에 의한 간 성상세포 증식 및 활성 억제효과

이기호, 진순우, 정혜광 충남대학교 약학대학 의약품개발연구소 2017 藥學論文集 Vol.32 No.-

During the process of liver fibrosis, hepatic stellate cells (HSCs) play a critical role in the increased formation and reduced degradation of extracellular matrix in the liver. Capsaicin (CPS) exerts many pharmacological effects. but any possible influence on HSCs remains unclear. Therefore. we evaluated the in-hibitory effects of CPS on Platelet-derived growth factor(PDGF)-BB-induced hepatic stellate cells (HSCs) proliferation and activation. The CPS suppressed HSC activation. including PDGF-BB-induced proliferation. u -smooth muscle actin (a-SMA) expression and collagen accumulation. Additionally, CPS inhibited PDGF-BB-induced Akt and ERK1/2 phosphorylation. Furthermore, in HSCs, CPS inhibited the PDGF-BB-in-duced increases in a一SMAand collagen type 1 expression. via Akt and ERK1/2 inhibition. These results in-dicate that CPS can ameliorate hepatic fibrosis by inhibiting the Akt and ERK1/2 pathway.

Tetrabromobisphenol A가 인간 유방암 세포 MCF-7에서 Fatty Acid Synthase 발현에 미치는 영향

김지연, 이기호, 진순우, 정혜광 충남대학교 약학대학 의약품개발연구소 2021 藥學論文集 Vol.36 No.-

Breast cancer is the most common malignant cancer and the major cause of mortality due to cancer in females worldwide, and the morbidity has increased gradually over recent years. Cancer cells require more energy and nutrients than normal cells for rapid growth and proliferation, which can be satisfied from lipids. Therefore, lipogenesis occurs more actively in cancer cells. In previous studies, fatty acid synthase (FASN) overexpression in breast cancer patients was found to be a poor prognostic factor for disease, suggesting the possibility of FASN inhibitor as a drug target in breast cancer treatment. protein kinase B (Akt) and AMP-activated protein kinase (AMPK) were reported to regulate sterol regulatory element-binding protein-1c (SREBP-1c) which is transcription facfor of FASN. Tetrabromobisphenol A (TBBPA), the most common industrial brominated flame retardant, acts as a cytotoxic, neurotoxic, and immunotoxicant, causing inflammation. However, despite the harmful effects of TBBPA, the effects and mechanisms of TBBPA on fatty acid synthesis in breast cancer cells are unclear. Therefore, this study investigated the effect of TBBPA on fatty acid synthesis in breast cancer cells. In human breast cancer MCF-7 cells, treatment with TBBPA significantly induced the expression of FASN and SREBP-1c. Furthermore, TBBPA induced phosphorylation of Akt and suppressed phosphorylation of AMPK. Taken together, these results suggest that TBBPA may induce lipid synthesis by regulating SREBP-1c via Akt and AMPK signaling pathway in breast cancer MCF-7 cells.

Induction of Cytochrome P450 1A and 2B by α-and β-Ionone in Sprague Dawley Rats

Jeong, Hye Gwang,Chun, Young-Jin,Yun, Chul-Ho,Moon, Chang-Kiu,Lee, Hye-Sook,Han, Sang Seop,Lee, Eung-Seok,Jeong, Tae Cheon 영남대학교 약품개발연구소 2002 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

β-lonone has been reported to induce the cytochrome P450 (P450) 2B1 in rats. In this study, the effects of and an isomer, α-lonone, on liver P450 1A and 2B experssion in Sprague Dawley rats were investigated. Subctaneous administration of α-and β-ionone 72 and 48hr prior to sacrificing the animals induced the liver microsomal P450 1A and 2B proteins. P450 2B1 induction was associated with the accumulation of its corresponding mRNA. Induction by β-ionone was much higher than that by α-ionone in both the mRNA and protein levels. When the route of administration was compared. P450 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of α- and β-ionone for 24 h induced P450 2B-1selective pantoxyresorufin O-depentylase activity comparably in a dose-dependent manner. In addition, α- and β-ionone might be potent P450 2B1 inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.