실험적 뇌지주막하출혈 토끼에서의 Malonate 농도 측정

김재중,하영수,백승렬,장정순,김유삼 대한신경외과학회 1995 Journal of Korean neurosurgical society Vol.24 No.10

Malonate is regarded as a reversible competitive inhibitor of succinate dehydrogenase and malate transport in the Krebs cycle and showed neurotoxicity by persistent NMDA receptor activation due to inhibition of ATP production and glutamate utilization. However, little was known about its biological effects and the range of normal concentration of malonate in central nervous system. In order to understand the relationship between malonate and vasospsasm, malonate concentrations in rabbit model of experimental subarachnoid hemorrhage were measured at 0, 4th, and 7th day following SAH in serum, cerebrospinal fluid, and urine using malonyl-CoA synthetase. The results were as follows : 1) Malonate level is increased significantly in serum at the 4th day after subarachnoid hemorrhage that followed by vasospasm(p<0.01). 2) CSF malonate concentration tends to increase at post-SAH 7th day but statistically not significant. 3) The change of urine malonate concentration is not significant. These results suggest that early increase of serum malonate level is significant because clinically important vasospam begin from the fourth through the seven day after hemorrhage. The increased level of serum malonate at this time is due to impairment of cellular metabolism following delayed cerebral ischemia and may influence to development of vasospasm. In conclusion, the measurement of serum malonate concentration after subarachnoid hemorrhage is one of possible candidates for the early diagnosis of vasospasm.

TPA로 야기된 HL-60 세포의 기질부착 저해작용을 이용한 Protein Kinase C 저해 생약의 탐색

김선희,안종석,김삼용,유관희,안병준 충남대학교 약학대학 의약품개발연구소 1993 藥學論文集 Vol.9 No.-

Thirty-five kinds of herbal drugs, believed to be active for treatment of tumors, were selected as the experimental materials for observing their effects on TPA-induced adherence of HL-60 cell and activity of protein kinase C. They were extracted with ethyl ether(E) and ethyl acetate(EA), methanol(M) in sequence. Among the extracts, Sophorae Flos(EA), Paeoniae Radix(EA), Equisetum hiemale(EA), Phellodendri Cortex(E, EA), Mori Cortex radicis(EA), Ferula assafoetida(E, EA), Sophora subprostrata(EA, M) and Cnidium monnieri(E) inhibited the TPA-in-duced adherence of HL-60 cell more than 50% and Sophorae Flos(E, EA, M), Paeoniae Radix(E, EA, M), Eguisetum hiemale(E), Phellodenri Cortex(E,H), Mori Cortex radicis(M), Ferula assafoetida(M), Sophora subprostrata(EA, M), Cnidium monnieri(M) and Artemisia argyi(M) showed inhibiting effects on the activity of protein kinase C more than 50%. The extracts showing good inhibiting effects on the adherence and enzyme activity were Sophorae Flos(EA), Paeoniae Radix(EA), Phellodendri Cortex(E), Sophora subsprostrate(EA) and Equisetum hiemale(EA).

진균성 부비동염 환자의 상악동내 농성 분비물에 대한 세균 배양 및 항생제 감수성 결과

이윤식,김용재,김재호,정유삼,이봉재 대한이비인후과학회 2000 대한이비인후과학회지 두경부외과학 Vol.43 No.10

The Effect of ZD 1839 (Iressa) in the Treatment of RefractoryNon Small Cell Lung Cancer

Yong Tai Kim,Chul Kim,Joo Hyuk Sohn,So Young Park,Soo Young Park,Nae Choon Yu,Young Sam Kim,Se Kyu Kim,Joon Chang,Kil Dong Kim,Kyung Young Chung,Joo Hang Kim 대한암학회 2003 Cancer Research and Treatment Vol.35 No.6

Purpose: The aim of this study was to evaluate theefficacy and the safety of ZD 1839 (Iressa) as a 3rd or4th line chemotherapy regimen in NSCLC patients whoare refractory to a previous chemotherapy regimen.Materials and Methods: Twenty-five patients who wererefractory to previous chemotherapy were selected forthis study. The eligible patients had an ECOG performancestatus of 0 to 2, and an appropriate end organfunction. ZD 1839 (Iressa) 250 mg/d was orally administereduntil the patients experienced disease progressionor unacceptable toxicity.Results: Twenty-five patients were analyzed. The medianage of the patients was 57 years. The response ratewas 12.0% with partial responses in 3 patients. Fourteenpatients (56%) remained in the stable disease state and8 patients progressed. The median overall survival was9.0 months (95% CI 6.7~11.2). The median progressionfree survival was 3 months (95% CI 2.2~3.8). Hematologicaltoxicities of grade 3 or 4 neutropenia, anemia andthrombocytopenia were absent. Non-hematological toxicitieswere grade 2 or 3 skin rashes in 10 (40.0%) patientsand 1 (4.0%) patient and grade 3 nausea in 3 (12.0%) patients.No patient failed to continue chemotherapy due toany drug-related adverse events.Conclusion: The results suggest that ZD 1839 (Iressa)monotherapy is effective and tolerable as a 3rd or 4th linesalvage treatment for NSCLC patients refractory to previouschemotherapy regimens. (Cancer ResTreat. 2003;35:502-506)

Microbial Malonyl - CoA Decarboxylase

Kim, Yu Sam,Kolattukudy, P. E. 생화학분자생물학회 1985 BMB Reports Vol.12 No.4

Malonyl-CoA decarboxylase was partially purified from Mycobacterium tuberculossi H37Ra. The molecular weight of the enzyme was 44,000 and the pI and pH optimum (were 6.7 and 5.5, respectively. The enzyme showed a typical Michaelis-Menten substrate saturation, with an apparent Km and V of 0.2mM and 3. 85μ㏖/min/㎎, respectively. It catalyzed decarboxylation of methylmaonyl-CoA only at 5% of the rate observed with malonyl-CoA, whereas malonic acid and succinyl-CoA were not decarboxylated. Antibodies prepared against malonyl-CoA decarboxylase from the uropygial glands of goose and rat liver mitochondria did not inhibit the bacterial enzyme. Avidin did not inhibit the enzyme suggesting that biotin was not involved in the reaction. Thiol-directed reagents inhibited the enzyme as did CoA, acetyl-CoA, propionyl-CoA, methylmalonyl-CoA, and succinyl-CoA. Malonyl-CoA decarboxylase was also partially purified from malonategrown Pseudomonas fluorescens. The molecular weight of this enzyme was 56,000 and the pH optimum and apparent Km were 5.5 and 1mM, respectively. Unlike the mycobacterial enzyme, this enzyme was insensitive to p-hydroxymercuribenzoate, acetyl-CoA, and propionyl-CoA, and it was less sensitive to inhibition by succinyl-CoA and CoA than the mycobacterial enzyme. The size and properties of the two bacterial enzymes suggest that these are quite unlike the mammalian and avian enzymes and that they constitute a different class of malonyl-CoA decarboxylases.

Arabidopsis Small Rubber Particle Protein Homolog SRPs Play Dual Roles as Positive Factors for Tissue Growth and Development and in Drought Stress Responses

Kim, Eun Yu,Park, Ki Youl,Seo, Young Sam,Kim, Woo Taek American Society of Plant Biologists 2016 PLANT PHYSIOLOGY - Vol.170 No.4

<P>Lipid droplets (LDs) act as repositories for fatty acids and sterols, which are used for various cellular processes such as energy production and membrane and hormone synthesis. LD-associated proteins play important roles in seed development and germination, but their functions in postgermination growth are not well understood. Arabidopsis (Arabidopsis thaliana) contains three SRP homologs (SRP1, SRP2, and SRP3) that share sequence identities with small rubber particle proteins of the rubber tree (Hevea brasiliensis). In this report, the possible cellular roles of SRPs in postgermination growth and the drought tolerance response were investigated. Arabidopsis SRPs appeared to be LD-associated proteins and displayed polymerization properties in vivo and in vitro. SRP-overexpressing transgenic Arabidopsis plants (35S:SRP1, 35S:SRP2, and 35S:SRP3) exhibited higher vegetative and reproductive growth and markedly better tolerance to drought stress than wild-type Arabidopsis. In addition, constitutive over-expression of SRPs resulted in increased numbers of large LDs in postgermination seedlings. In contrast, single (srp1, 35S:SRP2-RNAi, and srp3) and triple (35S:SRP2-RNAi/srp1srp3) loss-of-function mutant lines exhibited the opposite phenotypes. Our results suggest that Arabidopsis SRPs play dual roles as positive factors in postgermination growth and the drought stress tolerance response. The possible relationships between LD-associated proteins and the drought stress response are discussed.</P>

Malonate - Induced Isocitrate Lyase in Pseudomonas fluorescence

Kim, Yu Sam,Jang, Sei Heon 생화학분자생물학회 1987 BMB Reports Vol.14 No.2

Chlorinated dibenzodioxins are formed as contaminants in the manufacture of a variety of products which used chlorophenols and chlorobenzenes as starting materials. Among them 2, 3, 7, 8, -tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic contaminant produced during a commercial synthesis of the herbicide, 2, 4, 5-trichlorophenoxyacetic acid. In rats, TCDD caused a delayed onset, long term depression in the biliary excretion of ouabain that is maximal about 10 days after 10 or 25 ㎍/㎏ TCDD (Yang and Peterson, Toxicol. Appl. Pharmacol. 40:485, 1977). Our object was to determine if other halogenated dibenzo-p-dioxins also produce similar effects. A single dose of 2, 3, 7, 8-TCDD, 2, 3, 7-tribromodibenzo-p-dioxin (TBDD), 1, 2, 3, 7, 8, 9-hexachlorodibenzo-p-dioxin (HCDD), 1, 2, 4, 6, 7, 9-hexachlorodibenzo-pdioxin(HCDD), or 1, 3, 6, 8-tetrachlorodibenzo-p-dioxin (TCDD) was given to male rats (25 ㎍/㎏, po) and the biliary excretion of ouabain assessed 10 days later. Treatment of 2, 3, 7, 8-TCDD, 2, 3, 7-TBDD and to a lesser extent 1, 2, 3, 7, 8, 9-HCDD increased the plasma concentration of ouabain and decreased its excretion into bile. Comparing control rats to those treated with halogenated dibenzo-p-dioxin, percent recovery of ouabain in bile in 60 min was 62, 28, 34, and 50% (control, 2, 3, 7, 8-TCDD, 2, 3, 7-TBDD, and 1, 2, 3, 7, 8, 9-HCDD, respectively). Other two compounds 1, 2, 4, 6, 8, 9-HCDD and 1, 3, 6, 8-TCDD had no effects in biliary excretion of ouabain. The magnitude of depression in ouabain excretion by those compounds was closely related to the binding affinity of the compound to liver cytosol and their induction potency of aryl hydrocarbon hydroxylase (AHH) activity. This results support recent proposal of Poland and Glover that the toxic effects produced by halogenated aromatic hydrocarbons are mediated by their binding to a liver cytosol protein which is the induction receptor for enzyme including AHH(Mol. Pharmacol. 17:86, 1980).

Purification and Properties of Glcose - 6 - phosphate Dehydrogenase from the uropygial Gland of Duck

Kim, Yu Sam,Seo, Kyong Hoon 생화학분자생물학회 1988 BMB Reports Vol.15 No.4

NADPH for the biosynthesis of fatty acids was known to be generated mainly through pentose phosphate pathway and pyruvate-malate cycle in liver and adipose tissue. Since the uropygial gland is a specialized organ which produces surface lipid, it is interesting to examine the major NADPH supplying route in this gland. For this purpose, the activities of the key enzymes in the both pathways shown above were measured. The activity of the glucose-6-phosphate dehydrogenase was seven times higher than that of malic enzyme, suggesting that pentose phosphate pathway would be the major NADPH supplying route. Therefore the glucose-6-phosphate dehydrogenase was purified in 121 fold by 2', 5'-ADP agarose affinity chromatography and DEAF-sephacel ion exchange chromatography and its properties were characterized. The purity of the enzyme was over 95% and the molecular size of subunit determined by SDS PAGE was 57, 500 dalton. The optimum pH for the enzyme was 9∼10. Km and Vmax for glucose-6-phosphate and NADP were 10.1 μM, 4.41 μM and 250 μmole min^(-1) ㎎,^(-1) 207 mole min 1 ㎎^(-1) respectively. The enzyme showed high substrate specificity for glucose-6-phosphate and NADP, comparing with substrate analogs such as D-galactose-E-phosphate, 2-deoxy-glucose-6-phosphate and BAD. ATP was a non-competitive inhibitor to the both substrates, glucose-6-phosphate and NADP. On the other hand, NADPH was a non-competitive inhibitor to glucose-6-phosphate and competitise to NADP. Various nucleotides effected little on the activity of the enzyme at pH 9. Mg, Mn ions positively acted on the activity of the dehydrogenase and phosphate ion influenced negatively.

Isolation of Nihydrin Positive Compounds ( S ) Containing Esterase Activity from Pine Pollen

Kim, Yu Sam,Park, Jin Kyu 생화학분자생물학회 1988 BMB Reports Vol.15 No.4

A citomase, which hydrolyze cutin ester, was expected from pine pollen Therefore pine pollen was incubated in water. And esterase activity in the water extract was measured by using p-nitrophenyl acetate (PNA) and p-nitrophenyl palmitate (PNP) as model substrates. However, the compound(S) which hydrolyze PNA and PNP was not enzyme but ninhydrin-positive compound(S). One of the compound(S) was identified as glycine.

Monomer Composition of Pear and Persimmon Cutin

Kim, Yu Sam,Jang, Sei Heon,Espelie, Karl 생화학분자생물학회 1987 BMB Reports Vol.14 No.2

Monomer composition of pear and persimmon cutin was analyzed by a combined,; gas chromatography-mass spectrometry (GC-mass). Those cutins, which are surface biopolyesters covered the fruits, were isolated by treatment with ammonium oxalateoxalic acid and pectinase. The cutins, defatted by extraction, were depolymerized by metal hydride reduction. Ether extractable fraction of the reaction mixture w as silylated and analyzed by GC-mass. Persimmon cutin was composed of a relatively small number of monomers which is mainly w-hydoxy-9, 10-epoxyoctadecanoic acid (47.8%). Pear cutin was composed of a larger number of monomers which include long chain fatty alcohol, fatty acid and dicarboxylic acids indicating suberin characteristics. Relative amount of w-hydroxy-9, 10-epoxyoctadecanoic acid in pear cutin (76.1%) was considerably higher than that in persimmon cutin.