한국산 해양 의충동물 개불에서 Anthraquinone 및 Sterol 성분연구

장성근,박영현,채석,김인규,서영완,조기웅,신종헌,Chang, Sung-keun,Park, Yong-Hyun,Chai, Seuk,Kim, In-Kyu,Seo, Young-Wan,Cho, Ki-woong,Shin, Jong-Heon 대한화학회 1998 대한화학회지 Vol.42 No.1

한국 연해에 서식하고 있는 의충동물 개불(Urechis unicintus)로 부터 강심작용과 관련된 $Na^+,K^+-ATPase$ 저해 작용 및 cyclic AMP phosphodiesterase 저해 작용이 높은 anthraquinones화합물인 chrysophanol, physcion 및 1-o-methyl-2methoxychrysophanol을 분리하였다.주로 HMQC, HMBC 및 NOE 등의 분광학적 방법으로 이들의 구조를 밝혔다. Three anthraquinones, chrysophanol, physcion and 1-o-methyl-2-methoxychrysophanol which have $Na^+,K^+-ATPase$ and cyclic AMP phosphodiesterase lowering activities related to cardiotonic action were isolated from the Korean marine echiura, Urechis unicintus. Spectroscopic methods, including HMQC, HMBC and NOE studies, were used to establish the structures.

직업적인 크롬 노출이 혈중 Homocysteine, Folate와 Vitamin B12 농도에 미치는 영향

김기웅 ( Ki Woong Kim ),김규상 ( Kyoo Sang Kim ),박인정 ( In Jeong Park ),강성규 ( Seong Kyu Kang ),오성수 ( Sung Soo Oh ),정효석 ( Hyo Seok Jeong ),장성근 ( Sung Keun Chang ) 한국산업위생학회 2006 한국산업보건학회지 Vol.16 No.3

We evaluated the relations among exposure and urinary levels of Cr, folate, vitamin B12 and Hcy levels in the workers chronically exposure to Cr. Subjects were 104 male employees, 65 workers exposed to Cr in 9 electroplating plants and 39 office workers who had never been occupationally exposed to hazardous substances including Cr. The geometric mean(GM) of Cr in workplace was 0.069±0.101 ㎎/m3 and urinary Cr was 0.483±0.394 ㎎/g creatinine and airborne Cr concentration was significantly correlated to the urinary concentration of Cr(r=0.900, p=0.000). The geometric mean concentration of urinary Cr in control group was 0.301±0.255 ㎎/g creatinine. In comparing the workers exposed to Cr with controls, significantly higher mean plasma levels were found of Hcy(11.3±4.9 vs 9.4±4.7 μmol/ℓ, p=0.05), but vitamin B12 levels (181.8±68.7 vs 216.0±64.3 nmol/ℓ, p=0.01) was significantly decreased. Hcy concentrations correlated positively with airborne Cr concentrations(r=0.287, p=0.004) and urinary Cr concentrations(r=0.244, p=0.015) but folate concentrations correlated negatively with airborne(r=-0.234, p=0.020) and urinary Cr concentrations(r=-0.640, p=0.090), respectively. No correlations were observed between vitamin B12, airborne and urinary Cr concentrations. Also, Hcy concentrations correlated positively with vitamin B12(r=0.295, p=0.0020 and negatively with folate concentrations(r=-0.196, p=0.046). The various biological(i.e. age and serum indicates) or lifestyle factors(i.e. medication, smoking, alcohol and coffee intake), also taken into account as potential confounders, did not influence the correlations found. Thus, this study found evidence that Cr might be associated with elevated plasma levels of Hcy. Furthermore, elevated plasma levels of Hcy were significantly associated with folate and vitamin B12 concentration.

급성 납중독된 흰쥐의 이물질 대사효소의 활성도에 관한 연구

김기웅,송용범,장성근 ( Ki Woong Kim,Young Beam Song,Sung Keun Chang ) 생화학분자생물학회 1994 BMB Reports Vol.27 No.2

In rats treated with lead nitrate and/or red ginseng extract mixture we observed a change in the level of hepatic cytochrome P-450 and electron transport system for P-450 dependent reaction, and a content of zinc protoporphyrin (ZPP) and hemoglobin (Hb) in whole blood. The contents of cytochrome P-450 and b_5, and the activity of ECDEase, AHHase and NADPH-cytochrome C (P-450) reductase were slowly decreased according to the dosage of lead nitrate. On the other hand, the activity of NADH-bs reductase was increased according to the dosage of lead nitrate, but in case of treatment with red ginseng mixture, this enzyme activity was slightly decreased. In whole blood, the contents of hemoglobin and ZPP were not shown any critical change but lead content increased according to dosage of lead nitrate. These results suggest that content and activity of cytochrome P-450-dependent monooxygenase may be dependent on specificity of substrates and exposure duration.

벤젠 대사에 있어서 GST Subfamily와 NQO1 유전자다형성의 영향

정효석(Hyo Seok Jeong),김기웅(Ki-Woong Kim),이종은(Jong Eun Lee),이원택(Won Taek Lee),박경아(Kyung Ah Park),장성근(Sung Keun Chang) 대한해부학회 2003 Anatomy & Cell Biology Vol.36 No.4

본 연구는 정유회사 근로자 90명를 대상으로 하여 benzene의 노출농도와 대사산물인 phenol의 배설량을 측정한 후, benzene의 대사에 관여하는 glutathione S-transferase (GST)M1, GSTT1, GSTP1과 NAD(P)H: quinone oxidoreductase (NQO1) 유전자다형성을 분석하여 이들 효소의 유전자 아형 (genotype)에 따라 benzene의 대사에 어떠한 영향을 미치는지를 파악하고자 하였다. 연구 대상자들이 노출되는 benzene의 평균농도는 0.042±0.069 (mean±S.D) mg/m3이었고, 뇨중으로 배설되는 phenol의 평균 배설량은 7.42±11.3 (mean±S.D) mg/g creatinine으로, 상관성 (r)은 0.604 (p⁄0.01)이었다. benzene의 대사와 이들 효소의 유전자다형성에 대한 상관성을 보면, benzene의 대사산물인 phenol의 배설량과 GSTM1과 GSTT1 null 아형에서는 0.769과 0.863의 상관성을 보였고 (p⁄0.01), present 아형보다 다소 높은 상관성을 보였다. 또한 GSTP1의 경우에도 GSTP1*1/*1 유전자 아형이 GSTP1*1/*2 (r = 0.413, p⁄0.05)보다 높은 상관성을 보였다. 그리고 NQO1에서의 polymorphic site가 존재하는 아형(r = 0.833, p⁄0.01)과 존재하는 않는 유전자 아형 (r = 0.877, p⁄0.01)에서 비슷한 상관성을 보였다. 이러한 현상은 Cytochrome P450 2E1 CYP2E1에 의하여 benzene의 대사가 촉진되어 phenol의 생성이 증가되고, 포합반응 은 활성이 결여된 GST subfamily null 유전자 아형보다 present 아형에 의해서 이루어지는 것으로 보인다. 또한 NQO1의 경우에 polymorphic site가 있는 유전자와 없는 유전자 아형에서 비슷한 상관성을 보인 것은 phenol이 semiquinone계 물질로 대사 변형되는 기전보다 다른 기전을 통하여 대사 변형되는 경로가 우세하기 때문에 상대적으로 생성되는 물질의 양이 적어서 유전자 아형에 따른 차이를 보이지 않은 결과로 생각된다. The higher concentration of traces of aromatic hydrocarbons prevailing in the refinery atmosphere causes severe occupational health hazard to refinery workers. In this study, the biochemical role of genetic polymorphism in modulating urinary excretion of benzene metabolite as phenol level has been investigated in 90 workers exposed to benzene in the petroleum refinery plants of Korea. Glutathione S-transferase (GST) subfamily as GSTM1, GSTT1 and GSTP1 and NAD(P)H: quinone oxidoreductase 1 (NQO1) gene polymorphisms were determined by polymerase chain reaction (PCR)-based methods. The mean concentration of volatile benzene in the refinery environment was 0.042 mg/m3 (SD, 0.069) and that of urinary phenol was 7.42 mg/g creatinine (SD, 11.3). The airborne benzene concentration was significantly related to the concentration of phenol in urine (r = 0.640, p⁄0.01). However, all the genotypes of GST subfamily and NQO1 except small sample size of genotypes in GSTM1 and GSTT1 none of them were higher than that of present genotype. Also, it was higher in the GSTP1*1/*1 than in the GSTP1*1/*2. The various biological (i.e. age and liver function parameters) or lifestyle factors (i.e. medication, smoking, alcohol and coffee intake), also taken into account as potential confounders, did not influence the correlations found. These results suggested that GST subfamily and NQO1 genotypes might play an important role in the metabolism of benzene.

흰쥐에 있어서 납과 카드뮴이 Hepatic Microsomal Electron Transport System 활성도에 미치는 영향

김주봉,장성근,김기웅,송용범,김무호 순천향대학교 1994 논문집 Vol.17 No.3

In rats treated with lead nitrate and cadmium chloride we observed a change of he level of hepatic microsomal protein, cytochrome P-450 and ??, and electron transport system for P-450 dependent reaction. The contents of microsomal protein, P-450 and b5, and activity of NADPH-cytochrome C(P-450) reductase were decreased according to the dosage of lead nitrate and cadmium chloride. On the other hand, the activity of NADH-cytochrome ?? reductase was increased according to the dosage of lead nitrate and cadmium chloride. These results suggest that the content and activity of cytochrome dependent mono-oxygenase may be dependent on specificity of substrates, and electron transport occurred through two pathway, that is, NADPH-cytochrome C(P-450) reductase and ?? reductase but NADH-cytochrome ?? reductase was mainly act as a mobile carrier so-called second electron carrier.

흰쥐에 있어서 Styrene에 의한 간장의 Microsomal Cytochrome P450의 유도

이준연,박상신,정효석,문영한,김기웅,장성근 大韓産業醫學會 1997 대한직업환경의학회지 Vol.9 No.4

The effects of styrene on the induction of cytochrome P-450s (P450), (P4501A1/2, P4502B1/2 and P4502E1) and activities of other related enzymes were investigated in the male Sprague Dawley rats which were treated with styrene 500(S1), 1.000(S2), 1,500(S3) mg/kg in olive oil intraperitoneally once a day for two days and sacrificed for the preparation of liver microsomes after 24 hrs. 1. The contents of total protein and P450 in the microsomes derived from the styrene treated groups were slightly higher than those from the control group except those from the S3 group (1,500 mg styrene/kg body weight). The decreases in microsomal protein contents was prominent in the S3 (p<0.05), but the P450 contents was increased significantly in the S2(P<0.05). 2. The activities of NADPH-450 and NADH b5 reductase in hepatic microsomes derived from the treated groups were significantly increased in the treated groups (p<0.05). 3. The activities of PROD were also prominently increased with the treatment of styrene except in S3 group, but the activity of EROD was decreased by styrene treatment. The activities of pNPH in the styrene treated groups were higher than that of the control group(p<0.05). 4. Western blotting with monoclonal antibodies against P4502B1/2 isozymes showed the presence of P4502B1/2 in hepatic microsomes from the rats treated with styrene, and the increase in the densities of immunoblots were corelated with the dosages of styrene. The blot densities against P4501A1/2 and P4502E1 were slightly increased in the styrene treated groups compared with the control group. These results suggested that styrene could primarily induce P4502B1/2 as major and P4501A1/2 and P4502E1 in minor forms for the metabolism of styrene in rats.

혈중납이 흰쥐의 Microsomal Cytochrome P-450 Monooxygenase 활성도에 미치는 영향

박기현,장성근,윤영안,김기웅,박종안 순천향대학교 1993 논문집 Vol.16 No.3

In rats treated with lead nitrate and/or red ginseng extract mixture we observed a change in the level of hepatic cytochrome P-450 and electron transport system for P-450 dependent reaction, and content of Zincprotoporphyrin(ZPP) and Hemoglobin(Hb) in whole blood. The content of cytochrome P-450 and ?? , and the activity of ECHEase, AHHase and NADPH-cytochrome C(p-450) reductase were slowly decreased according to the dosage of lead nitrate. On the other hand, the activity of ?? reductase was increased according to the dosage of lead nitrate, but in case of treatment with red ginseng mixture, this enzyme activity was slightly decreased. In whole blood, the content of hemoglobin and ZPP were not shown any critival change but lead content increased according to dosage of lead nitrate. These results suggest that content and activity of cytochrome P-450-dependent monoxygenase may be dependent on specificity of substrates, and the acute exposure of lead nitrate and red ginseng extract mixture was not affected any biological significance.

수태가 Cytochrome P-450과 P-450 관련 효소들의 활성도와 유도성에 미치는 영향

김무호,장성근,송용범,박종안,김기웅 순천향대학교 1993 논문집 Vol.16 No.1

To clarify the characteristics on hepatic microsomal xenobiotics metabolism in non-pregnant female rats compared with the changes observed during pregnancy of rats, the activities and inducibility of cytochrome P-450(P-450) and its related enzymes in rat liver were measured. The content of P-450 and ??, and the activities of P-450 dependent arylhydrocarbon hydroxylase(AHH) and ethoxycoumarin deethylase(ECDE), and NADPH-reductase and NADH-cytochrome ?? reductase were increased during preganacy of rats treated with 3-methylcholanthrene(MC). Pregnancy did not result from the induction of any specific P-450 isozyme. The inducibility of P-450 by 3-MC was similar to that of non-pregnant rats, and MC has caused the induction of only P-450 c isozyme. These results suggest that although P-450 content was slightly increased overall xenobiotic metabolizing ability of microsomal mixed function oxidase and the inducibility of P-450 and its related enzymes by administration of MC are not significantly changed during pregnancy in SD rats, the homeostatic reaction of an organism for the xenobiotic metabolism was preserved and activated.