• 제목/요약/키워드: CoA transferase

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소아청소년기의 케톤분해이상질환군 (Ketolytic Defects in Children and Adolescents)

  • 최중완;안석민;김영한;백준우;류혜원;배은주;이홍진
    • 대한유전성대사질환학회지
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    • 제15권3호
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    • pp.147-154
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    • 2015
  • 목적: 우리나라 케톤분해이상질환군의 연령별분포, 임상양상 등을 알아보고자 본 연구를 시행하였다. 방법: 2007년 1월부터 2015년 9월 사이에 소변유기산분석을 시행하였던 2,794명의 환자 중에서 반복부하 유기산분석으로 진단된 67명의 케톤분해이상질환군환자들의 임상양상을 분석하였다. 결과: 케톤분해이상질환군 환자의 분포는 신생아기 1명, 영아기 30명, 소아기 31명, 청소년기 5명으로 나타났고, 가장 많은 주증상은 경련발작이었으며 발달지연을 동반한 경련발작, 발달지연 등이 뒤를 이었다. 결론: 우리나라의 발병빈도는 다른 나라에 비하여 높은 것으로 판단되며, 소아청소년과 의사들의 관심이 필요하다고 판단된다.

Effects of Culture Mechanism of Cinnamomum kanehirae and C. camphora on the Expression of Genes Related to Terpene Biosynthesis in Antrodia cinnamomea

  • Zhang, Zhang;Wang, Yi;Yuan, Xiao-Long;Luo, Ya-Na;Luo, Ma-Niya;Zheng, Yuan
    • Mycobiology
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    • 제50권2호
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    • pp.121-131
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    • 2022
  • The rare edible and medicinal fungus Antrodia cinnamomea has a substantial potential for development. In this study, Illumina HiSeq 2000 was used to sequence its transcriptome. The results were assembled de novo, and 66,589 unigenes with an N50 of 4413 bp were obtained. Compared with public databases, 6,061, 3,257, and 2,807 unigenes were annotated to the Non-Redundant, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes databases, respectively. The genes related to terpene biosynthesis in the mycelia of A. cinnamomea were analyzed, and acetyl CoA synthase (ACS2 and ACS4), hydroxymethylglutaryl CoA reductase (HMGR), farnesyl transferase (FTase), and squalene synthase (SQS) were found to be upregulated in XZJ (twig of C. camphora) and NZJ (twig of C. kanehirae). Moreover, ACS5 and 2,3-oxidized squalene cyclase (OCS) were highly expressed in NZJ, while heme IX farnesyl transferase (IX-FIT) and ACS3 were significantly expressed in XZJ. The differential expression of ACS1, ACS2, HMGR, IX-FIT, SQS, and OCS was confirmed by real-time quantitative reverse transcription PCR. This study provides a new concept for the additional exploration of the molecular regulatory mechanism of terpenoid biosynthesis and data for the biotechnology of terpenoid production.

생쥐에서의 인삼추출액의 장기간 투여에 의한 간장 DT-Diaphorase 활성의 증가 (Increase in Hepatic DT-Diaphorase Activity by Chronic Administration of Panax ginseng Extract to Mice)

  • Lee, Kang-Mee;Wie, Myung-Bok;Song, Dong-Keun;Kim, Yong-Sik;Kim, Yung-Hi
    • Journal of Ginseng Research
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    • 제17권2호
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    • pp.123-126
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    • 1993
  • Effects of chronic administration of ginseng extracts (30 or 150 mg/kg/day for 52 days, p.o.) to mice on the activities of DT-diaphorase and glutathione S-transferase (GST) in the liver and the brain were studied. The DT-diaphorase activity in the liver was increased over 2-fold at the dose of both 30 and 150 mg/kg/day, while there was no change in the activity of the enzyme in the brain. The GST activity in the liver was increased in a dose-dependent fashion up to 142% of the control value at the dose of 150 mg/kg/day. while there was no change in the activity of the enzyme in the brain. The ginseng-induced increase in the activities of these hepatic phase II drug-metabolizing enzymes which are involved in the detoxification of carcinogens, is suggested to underlie, at least in part, the anticarcinogenic activity of Panax ginseng.

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Comparative Genome Analysis of Psychrobacillus Strain PB01, Isolated from an Iceberg

  • Choi, Jun Young;Kim, Sun Chang;Lee, Pyung Cheon
    • Journal of Microbiology and Biotechnology
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    • 제30권2호
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    • pp.237-243
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    • 2020
  • A novel psychrotolerant Psychrobacillus strain PB01, isolated from an Antarctic iceberg, was comparatively analyzed with five related strains. The complete genome of strain PB01 consists of a single circular chromosome (4.3 Mb) and a plasmid (19 Kb). As potential low-temperature adaptation strategies, strain PB01 has four genes encoding cold-shock proteins, two genes encoding DEAD-box RNA helicases, and eight genes encoding transporters for glycine betaine, which can serve as a cryoprotectant, on the genome. The pan-genome structure of the six Psychrobacillus strains suggests that strain PB01 might have evolved to adapt to extreme environments by changing its genome content to gain higher capacity for DNA repair, translation, and membrane transport. Notably, strain PB01 possesses a complete TCA cycle consisting of eight enzymes as well as three additional Helicobacter pylori-type enzymes: ferredoxin-dependent 2-oxoglutarate synthase, succinyl-CoA/acetoacetyl-CoA transferase, and malate/quinone oxidoreductase. The co-existence of the genes for TCA cycle enzymes has also been identified in the other five Psychrobacillus strains.

Synthesis of a Novel Series of Imidazo[1,2-α]pyridines as Acyl-CoA: Cholesterol Acyltransferase (ACAT) Inhibitors

  • Jin, Ying-Lan;Rho, Mun-Chual;Gajulapati, Kondaji;Jung, Hwa-Young;Boovanahalli, Shanthaveerappa K.;Lee, Jee-Hyun;Song, Gyu-Yong;Choi, Jung-Ho;Kim, Young-Kook;Lee, Kyeong;Choi, Yong-Seok
    • Bulletin of the Korean Chemical Society
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    • 제30권6호
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    • pp.1297-1304
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    • 2009
  • A novel series of imidazo[1,2-$\alpha$]pyridines was designed, synthesized, and tested for their ability to inhibit acyl- CoA:cholesterol acyltransferase. Preliminary lead optimization efforts resulted in the identification of ACAT inhibitors represented by analogues 5b, 5c, 6a, 6c, 7b, and 7c. The ACAT inhibitory activity of these compounds was further established by potent inhibition of cholesteryl ester formation in HepG2 cells by a representative analogue 7b.

Nicorandil alleviated cardiac hypoxia/reoxygenation-induced cytotoxicity via upregulating ketone body metabolism and ACAT1 activity

  • Bai, Yan Ping;Han, Lei Sen
    • The Korean Journal of Physiology and Pharmacology
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    • 제23권1호
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    • pp.37-45
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    • 2019
  • To study the effect of nicorandil pretreatment on ketone body metabolism and Acetyl-CoA acetyltransferase (ACAT1) activity in hypoxia/reoxygenation (H/R)-induced cardiomyocytes. In our study, we applied H9c2 cardiomyocytes cell line to evaluate the cardioprotective effects of nicorandil. We detected mitochondrial viability, cellular apoptosis, reactive oxygen species (ROS) production and calcium overloading in H9c2 cells that exposed to H/R-induced cytotoxicity. Then we evaluated whether nicorandil possibly regulated ketone body, mainly ${\beta}$-hydroxybutyrate (BHB) and acetoacetate (ACAC), metabolism by regulating ACAT1 and Succinyl-CoA:3-ketoacid coenzyme A transferase 1 (OXCT1) protein and gene expressions. Nicorandil protected H9c2 cardiomyocytes against H/R-induced cytotoxicity dose-dependently by mitochondria-mediated anti-apoptosis pathway. Nicorandil significantly decreased cellular apoptotic rate and enhanced the ratio of Bcl-2/Bax expressions. Further, nicorandil decreased the production of ROS and alleviated calcium overloading in H/R-induced H9c2 cells. In crucial, nicorandil upregulated ACAT1 and OXCT1 protein expressions and either of their gene expressions, contributing to increased production of cellular BHB and ACAC. Nicorandil alleviated cardiomyocytes H/R-induced cytotoxicity through upregulating ACAT1/OXCT1 activity and ketone body metabolism, which might be a potential mechanism for emerging study of nicorandil and other $K_{ATP}$ channel openers.

당귀천궁복합물이 대퇴골 골절 동물모델에서 골 유합에 미치는 영향 (Effects of Extracts from Cnidium officinale and Angelica sinensis on Bone Fusion in Mice with Femoral Fracture)

  • 김상우;오민석
    • 한방재활의학과학회지
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    • 제34권2호
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    • pp.1-14
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    • 2024
  • Objectives The purpose of this study is to evaluate the fracture healing effect of extracts from Cnidium officinale and Angelica sinensis (CO/AS) in mice with femoral fracture. Methods C57BL/6 mice were randomly divided into normal, control (phospate-bufferd saline), positive control (tramadol), CO/AS extract 40 mg/kg and 80 mg/kg. By using Collier's method, all groups except normal group went through femoral fracture. Aspartate aminotransferase (AST), alanine transferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and creatinine were measured to evaluate the safety of CO/AS. Hematoxylin & eosin, Safranin O staining, x-ray, tensile and compressive force were conducted to assess the effect of CO/AS on fracture. Results The liver function test showed AST, ALT and LDH in CO/AS at 14th and 28th days were not significantly different compared with control group. The renal function test showed BUN in CO/AS at 14th days and BUN and creatinine in CO/AS at 28th days were significantly decreased compared with control group. The morphological & histological analysis and x-ray showed that CO/AS promoted cartilage and callus formation process compared with control group. The tensile and compressive forces test showed tensile in CO/AS 40 mg/kg and tensile & compressive forces in CO/AS 80 mg/kg were significantly increased compared with control group. Conclusions CO/AS extract showed the possibility that it promotes early fracture union and increases bone tensile and compressive strength, while does not have hepatotoxicity. In conclusion, CO/AS has a potential to promote healing of bone fracture and this study warranted the clinical usage of CO/AS at bone fracture.

위령선 추출물이 Human Neuroblastoma 세포주에서 $CoCl_2$에 의해 유도된 세포사멸에 미치는 보호효과 (Protective Effect of Clematidis Radix Extract on $CoCl_2$-induced Apoptosis in Human Neuroblastoma Cells)

  • 박정우;임형호
    • 한방재활의학과학회지
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    • 제24권2호
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    • pp.41-50
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    • 2014
  • Objectives The purpose of this study was to evaluate the effects of Clematidis radix extract on $CoCl_2$-induced apoptosis in SH-SY5Y human neuroblastoma cells. Methods In order to investigate the protective effect of Clematidis radix on $CoCl_2$-induced cytotoxicity in neuronal cells, MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, DAPI(4,6-diamidino-2-phenylindoleI) staining, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling) assay, DNA fragmentation assay and western blotting were performed on SH-SY5Y human neuroblastoma cells. Results Cells treated with $CoCl_2$ exhibited several apoptotic features, while cells pre-treated with Clematidis radix prior to $CoCl_2$ exposure showed a decrease in the occurrence of apoptotic features. $CoCl_2$ increased HIF-$1{\alpha}$ expression, in contrast, Clematidis radix treatment decreased $CoCl_2$-induced HIF-$1{\alpha}$ expression. Pre-treatment with the extract of Clematidis radix suppressed Bax, cytochrome c, and caspase-3 expressions, and also increased Bcl-2 expression in SH-SY5Y human neuroblastoma cells. Conclusions These results suggest that Clematidis radix may exert a protective effect on $CoCl_2$-induced apoptosis in SH-SY5Y human neuroblastoma cells.

Kinesin superfamily KIF1A와 결합하는 미세소관 불안정화 단백질 SCG10의 규명 (SCG10, a Microtubule-Destabilizing Factor, Interacts Directly with Kinesin Superfamily KIF1A Protein in Brain)

  • 문일수;석대현
    • 생명과학회지
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    • 제19권7호
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    • pp.859-865
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    • 2009
  • 미세소관은 세포골격단백질의 중요한 구성 단백질로 축삭돌기 내에서는 세포막 방향으로 정렬되어 있다. Kinesin superfamily (KIFs)는 세포 내에서 미세소관을 따라 세포 내 소포들을 운반하는 분자 자동차 (molecular motor) 단백질이다. 본 연구에서 우리는 효모 two-hybrid system을 사용하여 KIF1A의 coiled-coil 영역과 결합하는 단백질로 미세소관 불안정화 요소인 SCG10 단백질을 분리하였다. SCG10은 KIFs에서 KIF1A와만 특이적으로 결한 하며, KIF1A의 400에서 820아미노산 부위가 SCG10과의 결합에 필수적임을 효모 two-hybrid assay로 확인하였다. 또한 SCG10의 coiled-coil영역은 KIF1A와의 결합에 필수영역임을 확인하였으며 단백질간의 결합은 Glutathione S-transferase pull-down assay를 통하여 확인하였다. 생쥐의 뇌 파쇄액에 SCG10항체로 면역침강을 행하여 KIF1A를 확인한 결과KIF1A는 SCG10과 특이적으로 같이 침강하였다. 이러한 결과들은 KIF1A는 SCG10와 결합하여 SCG10이 포함된 소포를 미세소관을 따라 이동시킴을 시사한다.

Synthesis and Ligand Based 3D-QSAR of 2,3-Bis-benzylidenesuccinaldehyde Derivatives as New Class Potent FPTase Inhibitor, and Prediction of Active Molecules

  • Soung, Min-Gyu;Kim, Jong-Han;Kwon, Byoung-Mog;Sung, Nack-Do
    • Bulletin of the Korean Chemical Society
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    • 제31권5호
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    • pp.1355-1360
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    • 2010
  • In order to search new inhibitors against farnesyl protein transferase (FPTase), a series of 2,3-bis-benzylidenesuccinaldehyde derivatives (1-29) were synthesized and their inhibition activities ($pI_{50}$) against FPTase were measured. From based on the reported results that the inhibitory activities of dimers 2,3-bis-benzylidenesuccinaldehydes were higher than those of monomers cinnamaldehydes, 3D-QSARs on FPTase inhibitory activities of the dimers (1-29) were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The statistical qualities of the optimized CoMFA model II ($r^2{_{cv.}}$= 0.693 and $r^2{_{ncv.}}$= 0.974) was higher than those of the CoMSIA model II ($r^2{_{cv.}}$ = 0.484 and $r^2{_{ncv.}}$ = 0.928). The dependence of CoMFA models on chance correlations was evaluated with progressive scrambling analyses. And the inhibitory activity exhibited a strong correlation with steric factors of the substrate molecules. Therefore, from the results of graphical analyses on the contour maps and of predicted higher inhibitory active compounds, it is suggested that the structural distinctions and descriptors that contribute to inhibitory activities ($pI_{50}$) against FPTase will be able to applied new inhibitor design.