• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1992년도 제1회 신약개발 연구발표회 초록집
• /
• pp.42-42
• /
• 1992

ras oncogene은 암조직이나 transformed human cell line에서 거의 공통적으로 발견되는 oncogene으로서 그 product인 p2l 단백질은 C-terminal 25개의 아미노산 외에는 거의 동일한 배열을 가지고 있는 매우 conservative한 단백질이며 C-terminal cysteine이 carboxy methylation되어 있고 또한 palmitic acid와 같은 long chain fatty acid도 결합되어 있다. 보고된 바에 의하면 p21 protein의 palmitation은 ras protein의 세포막에 대한 친화력을 유지시키며 이와 같은 친화력은 cell transforming activity의 기본요건으로 알려져 있다. 이와 같은 관점에서 볼때 p21 단백질의 C-terminal processing현상을 new drug target으로, 즉 p2l 단백질의 C-terminal processing을 억제하므로서 cell transforming activity를 저해 할 수 있을 것이므로 생체내에 존재하는 p21 단백질 C-terminal processing 억제제의 identification 및 purification은 항암제 연구와 밀접한 관계가 있다. 구체적으로 farnesyl-protein transferase inhibitor 혹은 carboxyl methyl inhibitor의 identification 및 purification은 이같은 목적을 달성 할 수 있는 가능성이 크다.

• Preventive Nutrition and Food Science
• /
• 제3권1호
• /
• pp.62-66
• /
• 1998

The effect of dietary capsaicin (8-methyl-N-vanillyl-6-nonenamide, CAP) on drug-metabolizing enzyme activities was investigated in mice. Male ICR mice were divided into 4 groups and fed diets containing 0, 5, 20, 100 ppm CAP for 4 seeks. Hepatic drug-metabolizing enzyme activities and serum alanine aminotransferase and aspartate transaminease activities were measured. There was no difference in hepatic alanine aminotransferse and aspartate transaminase activities among the groups. Hepatic microsomal cytochrome P450 in CAP fed groups, but p-nitrophenol hydroxylase and the cytosolic acitivity of glutathione S-transferase activities were decreased in the dietary CAP supplemetned groups compared to the control. These results suggest that the dietary CAP at a low dose differentially modulates drug-metabolizing enzyme acitvities without causing hepatic toxicity.

• Journal of Interdisciplinary Genomics
• /
• 제5권1호
• /
• pp.1-4
• /
• 2023

Kleefstra syndrome is caused by chromosome 9q34.3 deletion or heterozygous mutations in the Euchromatin Histone Methyl Transferase 1 (EHMT1) gene. The prevalence is estimated 1:25,000 to 1:35,000. Intellectual disability, distinctive facial features, hypotonia in childhood can be accompanied. The spectrum of Kleefstra syndrome includes behavioral/psychiatric problems, hearing and visual impairments, seizures, congenital heart defects, genitourinary defects, and obesity. Therefore, it is necessary to understand the pathophysiology and various manifestation of Kleefstra syndrome and discussing with a multidisciplinary team will help diagnose and treat Kleefstra syndrome patients.

• 한국임상약학회지
• /
• 제16권2호
• /
• pp.155-164
• /
• 2006

Great inter-variability in drug response and adverse drug reactions is related to inter-variability of drug bioavailability, drug interaction and patient's disease and physyological state that cause change in absorption, distribution, metabolism and excretion of drugs. However, these alone do not sufficiently predict and explain inter-variability in drug response. In recent studies, it is reported that inter-variability in drug response and adverse drug reactions may largely resulted from genetically determined differences in drug absoption, distribution, metabolism and drug target proteins. Especially, the major human drug-metabolizing enzymes such as CYP450, N-acetyl tranferase, thiopurine S-methyl transferase, glutathione S-transferase are identified as the major gene variants that cause inter-individual variability in drug's response and adverse drug reactions. These variations may have most significant implications for those drugs that have narrow therapeutic index and serious adverse drug reactions. Therefore, the genetic variation such as polymorphisms in drug metabolizing enzymes can affect the response of individuals to drugs that are used in the treatment of depression, psychosis, cancer, cardiovascular disorders, ulcer and gastrointestinal disorders, pain and epilepsy, among others. This review describes the pharmacogenomics of the drug metabolizing enzymes associated with the drug response and its clinical applications.

• 한국균학회지
• /
• 제28권1호
• /
• pp.55-59
• /
• 2000

까치버섯(Polyozellus multiplex) 메탄올 추출물과 물 추출물은 산화 유발물질인 $H_2O_2$에 대하여 메탄올 추출물과 물 추출물에서 각각 53.5%, 29.4%의 생존율을 보여 까치버섯 추출물의 항산화 효과를 확인하였다. 까치버섯 메탄올 추출물과 물 추출물을 이용하여 동물에 강력한 발암물질인 MHNG를 투여한 후 항산화 효소계를 측정한 결과, 물 추출물은 항산화효소인 glutathione S-transferase(GST)와 superoxide dismutase(SOD) 활성과 조직내의 해독물질인 glutathione(GSH)의 함량을 높여 주었다. 또한 0.5%의 까치버섯 물 추출물은 암억제 유전자인 p53회 발현을 매우 증가시켰다. 이상의 결과로 까치버섯(Polyozellus multiplex)은 항산화 능이 있으며 특히, 물 추출물은 체내의 항산화 효소를 활성화시키고 항산화 물질의 함량을 높여주었고 암 억제유전자인 p53의 발현을 증가시켜 항암효과가 있음을 보여주었다.

• 한국환경농학회지
• /
• 제8권1호
• /
• pp.47-54
• /
• 1989

동양종(東洋種)꿀벌 (Apis cerana F.)에 대(對)한 살충제(殺蟲劑)의 독성(毒性) 및 해독능력(解毒能力)을 조사(調査)하고 농약한계 사용량 결정에 기여하기 위하여 7가지 대표적인 살충제의 꿀벌에 대한 독성 및 해독효소의 활성을 조사하였다. 효소 활성은 해독효소로 알려진 microsomal oxidases, glutathione S-transferasecs, esterase와 DDT-dehydrochlorinase를 조사했고 성충(成蟲)일벌의 중장(中腸)을 사용하여 측정하였다. $LC_{50}$치의 측정 결과는 다음과 같다. 1. 공시 살충제중 DDT가 19ppm으로 독성(毒性)이 가장 낮았고 EPN이 0.75ppm으로 독성(毒性)이 가장 강(强)했다. 2. 준치사농도(準致死濃度)의 농약(農藥)이 성충(成蟲)일벌의 microsomal oxidase에 미치는 영향은 malathion 및 demeton S-methyl 처리가 aldrin epoxidase활성을 저해시켰고 N-demethylase활성은 carbayl 처리구에서 증대(增大)되었다. 3. Glutathione S-transferase(DCNB conjugation)활성은 diazinon과 malathion처리구에서 증대되었다. 4. Esterase는 malathion 및 permethrin처리구에서 ${\alpha}-NA$ esterase 활성(活性)의 저해(沮害)를 보였고 carboxylesterase와 AchE 활성은 거의 영향이 없었다. 5. DDT-dehydrochlorinase 활성은 carbaryl, malathion과 demeton S-methyl 처리구에서 저해를 보였다.

• 대한의생명과학회지
• /
• 제16권1호
• /
• pp.25-32
• /
• 2010

Sprague-Dawley(SD) rats were orally administered with $N^G$-nitro-L-arginine methyl ester(L-NAME) which inhibits or blocks the production of nitric oxide from L-arginine in vascular endothelial cells and vessel tissue to statistically examine the effects of nitric oxide on some physiological changes such as blood pressure and heart rate, and to confirm the apoptosis induced by the suppressed nitric oxide activity in some related organs under light microscope. Systolic blood pressure significantly increased 28.5% by the chronic treatment of L-NAME for 8 weeks (P<0.001), no significant difference, however, was observed in heart rate between the control group and the L-NAME-treated group regardless of their age. Hematoxylin-eosin staining showed some histological alterations only in kidney among the examined organs; heart, liver, pancreas, and adrenal gland from the L-NAME-treated group. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) test showed a strong positive reaction, representing that the chronic treatment of L-NAME facilitates apoptosis, in the cortex and medulla of kidney, but not any significance detectable in the other organs. These results conclude that chronic treatment of L-NAME significantly increases blood pressure, and that the followed inhibition of nitric oxide synthesis occurs a typical inducement of apoptosis in kidney.

• BMB Reports
• /
• 제28권2호
• /
• pp.149-154
• /
• 1995

Protein methylase II (S-adenosyl-L-methionine : protein O-methyl-transferase, EC 2.1.1.24; PM II) was purified approximately 1250-fold from porcine testis by fractional precipitation and DEAE-cellulose chromatography, followed by gel filtration on a Sephadex G-75 column and HPLC on a Protein Pak 125 column. The molecular weight of the enzyme was estimated to be 33,000 daltons by SDS-PAGE, which agreed with the value determined by gel filtration. Isoelectric focusing of purified PM II showed a single protein species with an isoelectric point of 6.2. The optimum pH for the reaction was 6.0. The $K_m$ value of the enzyme was $1{\times}10^{-5}M$ with a $V_{max}$ value of 769 pmol/min/mg of enzyme. S-adenosyl-L-homocysteine is a competitive inhibitor of PM II with a $K_i$ value of $1.38{\times}10^{-6}M$.

• 생약학회지
• /
• 제31권3호
• /
• pp.351-356
• /
• 2000

The hepatoprotective effects of bergenin and its derivative, acetylbergenin, were evaluated against D-galactosamine-induced liver damage in rats. Bergenin is a C-glucoside of 4-O-methyl gallic acid that has been isolated from the cortex of Mallotus japonicus (Euphorbiaceae). Acetylbergenin was synthesized from acetylation of bergenin to increase lipophilic and physiological activities. Bergenin (50, 100 and 200 mg/kg) and acetylbergenin (25, 50 and 100 mg/kg) were administered orally once daily for successive 5 days after the injection of galactosamine (400 mg/kg, i.p.), respectively. The substantially elevated serum enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and ${\gamma}-glutamyltransferase$ due to galactosamine treatment were dose-dependently restored towards normalization by post-treatment with bergenin and acetylbergenin. Bergenin and acetylbergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content induced by galactosamine in a dose-dependent manner. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. These results suggest that effects of bergenin and acetylbergenin may be related to complex mechanisms that involve prevention of lipid peroxidation and preservation of hepatic glutathione. The results of this study clearly indicate that bergenin and acetylbergenin have potent hepatotherapeutic action against galactosamine-induced hepatotoxicity in rats, and lipophilic acetylbergenin is more active in the antihepatotoxic effects against galactosamine than much less lipophilic bergenin.

• Biomolecules & Therapeutics
• /
• 제8권4호
• /
• pp.293-298
• /
• 2000

Bergenin is a C-glucoside of 4-O-methyl gallic acid that has been isolated from the cortex of Mallotus japonicus (Euphorbiaceae). Acetylbergenin was synthesized by acetylation from bergenin to increase lipophilic and physiological activities. The therapeutic effects of bergenin and acetylbergenin were evaluated against carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. Bergenin and acetylbergenin were administered orally once daily for successive 5 days, after the intraperitoneal injection of a mixture 0.5 m1/kg of $CCl_4$ in olive oil (1:1). The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and ${\gamma}$-glutamyltransferase induced by $CCl_4$ were restored towards normalization by posttreatment with bergenin and acetylbergenin. Bergenin and acetylbergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of glutathione content induced by $CCl_4$ in a dose dependent fashion. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. These results suggest that therapeutic effects of bergenin and acetylbergenin may be related complex mechanisms that involve prevention of lipid peroxidation and preservation of hepatic GSH. The results of this study clearly indicate that bergenin and acetylbergenin have potent hepatothrapeutic action against $CCl_4$-induced hepatotoxicity in rats. In addition, acetylbergenin 50 mgHg showed almost the same levels of hepatoprotective activity as those of bergenin 100 mgAg, indicating the fact that lipophilic acetylbergenin is more effective in the hepatoprotective action against $CCl_4$ than bergenin.