Phenylethanolamine N-methyltransferase: 부신, 뇌간, 시상하부 효소의 조절

전양숙,서유헌,Chun, Yang-Sook,Suh, Yoo-Hun 대한약리학회 1996 대한약리학잡지 Vol.32 No.2

To determine the regulatory mechanism of phenylethanolamine N-methyltransferase (PNMT) in the adrenal gland and in central nervous system, we observed the change of enzyme activity and mRNA level of PNMT in the adrenal gland, the brain stem, and hypothalamus of rats, which were injected with two neuroleptic agents(reserpine and haloperidol ). Reserpine depleting catecholamines in presynaptic vesicle increased PNMT activities in the adrenal gland and the brain stem to 150% of the control in time-dependent manner, but not in the hypothalamus. Haloperidol blocking dopamine receptor decreased PNMT activities in the adrenal gland and the hypothalamus, but not in the brain stem. Thus, the results indicate that catecholamines inhibit synthesis of epinephrine in the brain stem and the adrenal gland, and that dopamine stimulates synthesis of epinephrine in the hypothalamus and the adrenal gland. In addition, since the change of mRNA levels were nearly in accordance with the change of activities, the transcriptional regulation of PNMT is considered the mechanism of the regulation of epinephrine neuron.

Characterization of Plasma Membrane-associated NADPH and NADH Oxidoreductases in Bovine Liver

Yang-Sook Chun(전양숙),Jong-Wan Park(박종완) 한국실험동물학회 1999 Laboratory Animal Research Vol.15 No.3

Session E : Enzymes : Mechanism of Action and Regulation : TISSUE SPECIFICITY OF RAT PHENYLETHANOLAMINE - N - METHYLTRANSFERASE

서유헌,전양숙,최웅,김성수,박찬웅,김종국 ( Yoo Hun Suh,Yang Sook Chun,Woong Choi,Sung Soo Kim,Chan Woong Park,Jong Gook Kim ) 한국생화학분자생물학회 (구 한국생화학회) 1993 추계학술대회집 Vol.- No.-

Molecular Cloning of Human Genomic DNA for Epinephrine Synthesizing Enzyme, Phenylethanolamine N-Methyltransferase

서유현,허성오,전양숙,김현식,임정규,박찬웅,Suh, Yoo-Hun,Huh, Sung-Oh,Chun, Yang-Sook,Kim, Hun-Sik,Lim, Jung-Kyoo,Park, Chan-Woong The Korean Society of Pharmacology 1988 대한약리학잡지 Vol.24 No.1

카테콜아민 생합성에 관여하는 마지막 효소인 phenylethanolamine N-methyltransferase는 Norepinephrine을 epinephrine으로 전환시키는 중요한 효소이다. PNMT효소의 발현은 epinephrine 신경세포의 발현에 필수적이다. 따라서 PNMT유전자를 크로닝하여 그 구조를 결정하고, 유전자 발현연구를 하는 것은 상당히 중요한 일이다. 그러나 최근에 저자가 bovine cDNA를 처음으로 분리하여 그 구조를 보고한 것 외에는 아직까지 인간 PNMT cDNA나, 전체 genomic DNA의 분리 보고는 없다. 이에 저자들은 인간 PNMT유전자의 전체구조와 여러 종(species) 사이의 진화적인 관계를 규명하기 위해서 human genomic library(Charon 4A)를 만들고, 이 library 이용하여 bovine cDNA를 probe로 13.1 Kb길이의 genomic clone을 분리 크로닝하는데 성공하였다. 이 유전자는 두개의 EcoRI site가 포함되어 있어서, EcoRI제한효소에 의해서 7.5 Kb, 5.0 Kb,0.6 Kb로 분리되었으며, Southern과 dot blot 실험 에서 보면 5.0 Kb와 0.6 Kb에 exon이 흩어져 존재하고 있으며, 7.5 Kb는 flanking sequence로 판명되었다. To obtain information about the structure of the human phenylethanolamin N-methyltransferase (PNMT) and to further define the extent of the evolutionary relationships among PNMT molecules of several spesies, a full length cDNA clone for bovine adrenal PNMT was used to screen a charon 4A genomic library. One phage was isolated and identified, which included the entire PNMT gene. The length of inserted genomic DNA was 13.1-Kilobase (Kb) containing two internal EcoRI sites. Construction of a restriction map and subsequent Southern and dot blot analysis with 5'-and3'-specific cDNA probes allowed the identification of exon-containing fragments. This is the first report of the cloning of gene for human epinephrine synthesizing enzyme.

허혈/재관류 심장의 산화손상에서 미토콘드리아의 역할

박종완(Jong-Wan Park),전양숙(Yang-Sook Chun),김명석(Myung-Suk Kim) 대한약리학회 1996 대한약리학잡지 Vol.32 No.2

Restoration of the blood flow after a period of ischemia is accompanied by generation of toxic oxygen radicals. This phenomenon may account for the occurrence of reperfusion-mediated tissue injury in ischemic hearts. In in vitro studies, although oxygen radicals can be generated from a variety of sources, including xanthine oxidase system, activated leucocytes, mitochondria and others, the most important source and mechanism of oxygen radical production in the post-ischemic reperfused hearts is unclear. In the present study, we tested the hypothesis that the respiratory chain of mitochondria might be an important source of oxygen radicals which are responsible for the development of the reperfusion injury of ischemic hearts. Langendorff-perfused, isolated rat hearts were subjected to 30 min of global ischemia at 37˚C, followed by reperfusion. Amytal, a reversible inhibitor of mitochondrial respiration, was employed to assess the mitochondrial contributions to the development of the reperfusion injury. Intact mitochonria were isolated from the control and the post-ischemic reperfused hearts. Mitochondrial oxygen radical generation was measured by chemiluminescence method and the oxidative tissue damage was estimated by measuring a lipid peroxidation product, malondialdehyde(MDA). To evaluate the extent of the reperfusion injury, post-ischemic functional recovery and lactate dehydrogenase(LDH) release were assessed and compared in Amytal-treated and -untreated hearts. Upon reperfusion of the ischemic hearts, MDA release into the coronary effluent was markedly increased. MDA content of mitochondria isolated from the post-ischemic reperfused hearts was increased to 152% of preischemic value, whereas minimal change was observed in extramitochondrial fraction. The generation of superoxide anion was increased about twice in mitochondria from the reperfused hearts than in those from the control hearts. Amytal inhibited the mitochondrial superoxide generation significantly and also suppressed MDA production in the reperfused hearts. Additionally, Amytal prevented the contractile dysfunction and the increased release of LDH observed in the reperfused hearts. In conclusion, these results indicate that the respiratory chain of mitochondria may be an important source of oxygen radical formation in post-ischemic reperfused hearts, and that oxygen radicals originating from the mitochondria may contribute to the development of myocardial reperfusion injury.

Epinephrine 합성효소인 phenylethanolamine N-methyltransferase의 인간 genomic DNA의 유전자 크로닝

서유현(Yoo Hun Suh),허성오(Sung Oh Huh),전양숙(Yang Sook Chun),김현식(Hun Sik Kim),임정규(Jung Kyoo Lim),박찬웅(Chan Woong Park) 대한약리학회 1988 대한약리학잡지 Vol.24 No.1

카테콜아민 생합성에 관여하는 마지막 효소인 phenylethanolamine N-methyltransferase는 Norepinephrine을 epinephrine으로 전환시키는 중요한 효소이다. PNMT효소의 발현은 epinephrine 신경세포의 발현에 필수적이다. 따라서 PNMT유전자를 크로닝하여 그 구조를 결정하고, 유전자 발현연구를 하는 것은 상당히 중요한 일이다. 그러나 최근에 저자가 bovine cDNA를 처음으로 분리하여 그 구조를 보고한 것 외에는 아직까지 인간 PNMT cDNA나, 전체 genomic DNA의 분리 보고는 없다. 이에 저자들은 인간 PNMT유전자의 전체구조와 여러 종(species) 사이의 진화적인 관계를 규명하기 위해서 human genomic library(Charon 4A)를 만들고, 이 library 이용하여 bovine cDNA를 probe로 13.1 Kb길이의 genomic clone을 분리 크로닝하는데 성공하였다. 이 유전자는 두개의 EcoRI site가 포함되어 있어서, EcoRI제한효소에 의해서 7.5 Kb, 5.0 Kb,0.6 Kb로 분리되었으며, Southern과 dot blot 실험 에서 보면 5.0 Kb와 0.6 Kb에 exon이 흩어져 존재하고 있으며, 7.5 Kb는 flanking sequence로 판명되었다. To obtain information about the structure of the human phenylethanolamin N-methyltransferase (PNMT) and to further define the extent of the evolutionary relationships among PNMT molecules of several spesies, a full length cDNA clone for bovine adrenal PNMT was used to screen a charon 4A genomic library. One phage was isolated and identified, which included the entire PNMT gene. The length of inserted genomic DNA was 13.1-Kilobase (Kb) containing two internal EcoRI sites. Construction of a restriction map and subsequent Southern and dot blot analysis with 5 -and 3 -specific cDNA probes allowed the identification of exon-containing fragments. This is the first report of the cloning of gene for human epinephrine synthesizing enzyme.

선천성 고혈압 성장 백서에서의 카테콜아민 합성효소에 관한 연구

서유헌,전양숙,최웅,김헌식,임정규,김성수,박찬웅,조현섭 대한내분비학회 1989 Endocrinology and metabolism Vol.4 No.3

Central catecholaminergic nerves have an integral place in the central connections of the autonomic nervous system. It has long been thought that sympathetic nervous system plays an importantpart in the regulation of blood pressure, but there is no firm evidence of excessive activity of the sympathetic nervous system in development and maintenance of essential hypertension. It seems clear that central catecholaminergic systems participate in the regulation of normal blood pressure. However, it is not yet clear which system is altered in hypertension and which changes are of primary causal importance and which are secondary in nature. In the present study, we investigated activities of catecholamine synthesizing enzymes tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), phenylethanolamine N-methyl transferase (PNMT) in various regions of the brain and the adrenals in spontaneous hypertensive (SH) and normotensive wistar rats at 16 weeks of age when the hypertension is fixed. TH, DBH and PNMT activities n the adrenal glands of SH rats were significantly higher than that those of normotensive wistar rats. TH activity was higher in the hypothalamus of SH rats than that of wistar control rats. In the medulla, DBH activity of SH rats was lower than that of wistar rats. But PNMT activity was higher in the medulla of SH rats than that of wistar rats. These results suggest the possibility of over-activity of the adrenal medulla of SH rats and a participation of both norepinephrine and epinephrine neurons in the maintenance of hypertension. (J. Kor Soc Endocrinol 4:231~239, 1989)