• Title, Summary, Keyword: ATP

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Valproic Acid Reduces Reactive Oxygen Species in Fibroblast of X-linked Adrenoleukodystrophy (부신백질형성장애증 섬유모세포에서 발프로산의 항산화능)

  • Kang, Joon Won;Quan, Zhejiu;Jang, Jiho;Kang, Hoon-Chul
    • Journal of the Korean Child Neurology Society
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    • v.23 no.2
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    • pp.45-50
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    • 2015
  • Purpose: X-linked adrenoleukodystrophy (X-ALD) is a fatal, axonal demyelinating, neurodegenerative disease, and is caused by mutations the in ABCD1 (ATP-binding cassette transporter subfamily D member 1). Oxidative damage of proteins caused by very long chain fatty acid accumulating in X-ALD, is an early event in the neurodegenerative cascade. We evaluated valproic acid (VPA) as a possible option for oxidative damage in X-ALD. Method: We generated fibroblast of the childhood cerebral ALD from patient. We evaluated mRNA (ribonucleic acid) level of ABCD2 by real-time polymerase chain reaction, and reactive oxygen species (ROS) levels by flow cytometry. Results: VPA increased expression of ABCD2 in both control and ALD fibroblast. ABCD2 gene mRNA expression was increased 1.76 fold in normal fibroblasts, and 2.22 fold in the X-ALD fibroblasts. ROS levels were decreased in VPA treated X-ALD fibroblast, especially in treated with 1 mM of VPA. ROS levels revealed 13.7 in control fibroblast, on the other hand, 5.83 in X-ALD fibroblast treated with 1 mM of VPA. Conclusion: We propose VPA as a promising novel therapeutic approach in oxidant damage that warrants further clinical investigation in X-ALD.

Potential Antitumor Activity of SIM-89 in Non-Small Cell Lung Cancer Cells

  • Pei, Jun;Chu, Tianqing;Shao, Minhua;Teng, Jiajun;Sha, Huifang;Gu, Aiqing;Li, Rong;Qian, Jialin;Mao, Weifeng;Li, Ying;Han, Baohui
    • Yonsei Medical Journal
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    • v.58 no.3
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    • pp.581-591
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    • 2017
  • Purpose: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. Materials and Methods: Z'-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. Results: c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the $IC_{50}$ values of 297 nmol/L, $1.31{\mu}mol/L$, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. Conclusion: In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.

Relationship of Metabolic Diseases with Physical Activity Depending on Age (연령별 신체활동에 따른 대사성질환과의 관계)

  • Lim, Hyo Kyung;Sull, Jae Woong;Park, Beom Seok;Mun, Ji Young;Hong, Min Hwa;Lee, Yoori;Hwang, Min Ji;Lee, Mi Na;Lee, Ji Young;Kim, In Sik
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.2
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    • pp.144-154
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    • 2018
  • Metabolic disease is associated with abdominal obesity, high blood pressure, and dyslipidemia. Physical activity has beneficial effects on a variety of diseases. This study examined the relationship between metabolic diseases and physical activity according to age. Among a total of 7,295 subjects, the data from 382 individuals in the normal group and 1,525 persons in the metabolic disease group were analyzed. The data were analyzed statistically by one-way ANOVA, the Pearson's correlation coefficient, and multiple regression analysis. The levels of hemoglobin (HB), hematocrit (HCT), and creatinine (CR), were elevated when a high-intensity physical activity was performed, but they were reduced when a low-intensity physical activity was performed in the normal group aged 10~29 years and the metabolic disease group aged 50~69 years. In the normal group and metabolic disease group aged 30~49 years, the level of high density lipoprotein cholesterol (HDL-C) was elevated when high-intensity physical activity was conducted, whereas it was reduced when low-intensity physical activity was performed. No difference in the level of HDL-C depending on age and exercise intensity was observed in the normal group; the level of HDL-C decreased with age and increased with exercise intensity in the metabolic disease group. Physical activity has different effects in metabolic disease depending on age.

Study of Hedyotis Diffusa Methanol Extract on Anti-tumoral Effect and Mechanism (백화사설초(白花蛇舌草) 메탄올 추출물(抽出物)의 항종양(抗腫瘍) 효과(效果) 및 항암(抗癌) 기전(機轉)에 관(關)한 연구(硏究))

  • No, Hoon-Jeong;Moon, Gu;Moon, Seok-Jae;Won, Jin-Hee;Moon, Young-Ho;Park, Rae-Gil
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.6 no.1
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    • pp.81-97
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    • 2000
  • Objectives: This experimental study was carried out to evaluate the effects of aqueous and methanol extracts of Hedyotis diffusa which has long been used for cancer treatment in oriental medicines on the induction of apoptotic cell death in human lymphoid leukemia cell line, HL-60. Methods: Cells were treated with various concentrations (200 to $0.4{\mu}g$) and periods (6 to 30 hr) of $H_2O$ and methanol extracts of Hedyotis diffusa. Then, cells were tested for viability by MTT assay. Cells wrere treated with $200{\mu}g/ml$ of methanol extract fork various periods. Genomic DNA was isolated, separated, on 1.5% agarose gels, stained with ethidium bromide and visualized under UV light. Cells were treated with $200{\mu}g/ml$ of each extract for 16 hr. Then, cells were treated with Hoechst dye 33342 and observed by fluorescence microscopy. Cells were treated with various doses of each for 12 hr and $100{\mu}g/ml$ of methanol extract for various periods. Lysate from the cells used to measure the activity of Caspase-1 and-3 proteases by using fluorogenic peptide substrates including acetyl-YVAD-AMC and acetyl-DEVD-AMC, respectively. Cells were treated with $200{\mu}g/ml$ of each extract for various periods. Cell lysates were immunoprecipated with anti-JNKl antibodies. The immune complex was reacted with $32^p-ATP$ and c-Jun as a substrate. The phosphotransferase activity of JNKI was measured by using PhosphoImage analyzer (Fuji Co., Japan). Nuclear extracts were isolated and incubated with oligonucleotide probe of $NF-{\kappa}B$. Transcriptional activation of ${\kappa}B$ was measured by using EMSA and visualized by PhosphoImage analyzer (Fuji Co, Japan). Cell lysates were prepared and analyzed by Western blotting with anti-Bc12 antibodies and anti-Bax antibodies. Cells were pretreated with various doses of methanol extract for 2 hr. Then, the extract was removed by centrifugation. Cells were resuspended with RPMI-1640 media containing 0.3% agarose, 10% FBS, overlayred onto bottom layer agarose and incubated at $CO_2$ incubator for 6 days. The number of colony was counted under light microscopy ($\time100$). Results: The death of HL-60 cells was markedly induced by the addition of methanol extract of Hedyotis diffusa in a dose and time-dependent manners. The apoptotic characteristic ladder pattern of DNA strand break was observed in death of HL-60 cells. In addition, it was shown nucleus chromatin condensation and fragmentation under Hoechst staining. Therefore, Hedyotis diffusa extract-induced death of HL-60 cells is mediated by apoptotic signaling processes. The activity of Caspase 3-like proteases remained in a basal level in HL-60 cells treated with aqueous extract of Hedyotis diffusa. However, it was markedly increased in HL-60 cells treated with methanol extract of Hedyotis diffusa. In addition, the phosphotransferase activity of JNKl was increased in HL-60 cells treated with methanol extract of Hedyotis diffusa. Furthermore, the activation of transcriptional activator, $NF-{\kappa}B$ was markedly induced by methanol extract of Hedyotis diffusa. Anti-apoptotic Bc12 was cleaved into 23Kda fragment by treatment of methanol extract of Hedyotis diffusa. However, expression of proapoptotic Bax protein was increased by treatment of methanol extract of Hedyotis diffusa in a time-dependent manner. Furthermore, methanol extract markedly inhibited the colony forming efficiency of HL-60 cells in semisolid agar culture. Conclusions: Above results suggest that methanol extract of Hedyotis diffusa induces the apoptotic death of human leukemic HL-60 cells via activations of Caspase-3 proteases, JNKI, transcriptional activator $NF-{\kappa}B$, In addition, our results also suggest that methanol extract of Hedyotis diffusa reduces the malignant potential of HL-60 cells via down regulation of colony forming effciency through cleavage of Bc12 as well as induction of Bax.

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Effects of Pinacidil, a Potassium-Channel Opener, on Biodistribution of Thallium-201 in Tumor-Bearing Mice ($K^+$ 통로개방제 Pinacidil이 종양이식 생쥐에서 Tl-201의 체내분포에 미치는 영향)

  • Lee, Jae-Tae;Chun, Kyung-Ah;Lee, Sang-Woo;Kang, Do-Young;Ahn, Byeong-Cheol;Jun, Soo-Han;Lee, Kyu-Bo;Ha, Jeoung-Hee
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.4
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    • pp.303-311
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    • 2000
  • Purpose: Thallium behaves similarly to potassium in vivo. Potassium channel opener (K-opener) opens ATP-sensitive $K^+$-channel located at cell membrane, resulting in potassium efflux from cytosol. We have previously reported that K-opener can alter biokinetics of Tl-201 in cultured cells and in vivo. Malignant tumor cells have high Na-K ATPase activity due to increased metabolic activities and dedifferentiation, and differential delineation of malignant tumor can be possible with Tl-201 imaging. K-opener may affect tumoral uptake of Tl-201 in vivo. To investigate the effects of pinacidil (one of the potent K-openers) on the localization of the tumor with Tl-201 chloride, we evaluated the changes in biodistribution of Tl-201 with pinacidil treatment in tumor-bearing mice. Materials and Methods: Baltic mice received subcutaneous implantation of murine breast cancer cells in the thigh and were used for biodistribution study 3 weeks later. $100{\mu}g$ of pinacidil dissolved in $200{\mu}l$ DMSO/PBS solution was injected intravenously via tail vein at 10 min after 185 KBq ($5{\mu}Ci$) Tl-201 injection. Percentage organ uptake and whole body retention ratio of Tl-201 were measured at various periods after injection, and values were compared between control and pinacidil-treated mice. Results: Pinacidil treatment resulted in mild decrease in blood levels of Tl-201, but renal uptakes were markedly decreased at 30-min, 1- and 2-hour, compared to control group. Hepatic, intestinal and muscular uptake were not different. Absolute percentage uptake and tumor to blood ratios of Tl-201 were lower in pinacidil treated mice than in the control group at all time points measured. Whole body retention ratio of Tl-201 was lower in pinacidil treated mice ($58{\pm}4%$ ), than in the control group ($67{\pm}3%$) at 24 hours after with injection of $100{\mu}g$ pinacidil. Conclusion: K-opener did not enhance, but rather decreased absolute tumoral uptake and tumor-to-blood ratios of Tl-201. Decreased whole body retention ratio and renal uptake were observed with pinacidil treatment in tumor-bearing mice.

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Sequencing analysis of the OFC1 gene on the nonsyndromic cleft lip and palate patient in Korean (한국인 비증후군성 구순구개열 환자의 OFC1 유전자의 서열 분석)

  • Kim, Sung-Sik;Son, Woo-Sung
    • The korean journal of orthodontics
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    • v.33 no.3
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    • pp.185-197
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    • 2003
  • This study was performed to identify the characteristics of the OFC1 gene (locus: chromosome 6p24.3) in Korean patients, which is assumed to be the major gene behind the nonsyndromic cleft lip and palate. The sample consisted of 80 subjects: 40 nonsyndromic cleft lip and palate patients (proband, 20 males and females, mean age 14.2 years); and 40 normal adults (20 males and 20 females, mean age 25.6 years). Using PCR-based assay, the OFC1 gene was amplified, sequenced, and then searched for similar protein structures. Results were as follows: 1. The OFC1 gene contains the microsatellite marker 'CA' repeats. The number of the reference 'CA' repeats was 21 times, and formed as TA(CA)11TA(CA)10. But, in Koreans, the number of tandem 'CA' repeats was varied from 17 to 26 except 18, and 'CA' repeats consisted of TA(CA)n. 2. Nine allelic variants were found. Distribution of the OFC1 allele was similar between the patients and control group. 3. There was a replacement of the base 'T' to 'C' after 11 tandem 'CA' repeats in Koreans compared with Weissenbach's report. However, the difference did not seem to be the ORF prediction results between Koreans and Weissenbach's report. 4. The BLAST search results showed the Telomerase reverse transcriptase (TERT) and the Nucleotide binding protein 2 (NBP2) as similar proteins. The TERT was a protein product by the hTERT gene in the locus 5p15.33 (NCBI Genome Annotation; NT023089) The NBP2 was a protein product by the ABCC3 (ATP-binding cassette, sub-family C) gene in the locus 17q22 (NCBI Genome Annotation; NT010783). 5. In the Pedant-Pro database analysis, the predictable protein structure of the OFC1 gene had at least one transmembrane region and one non-globular region.

숙성 토하젓의 기능성분 및 토하젓 소스 개발에 관한 연구

  • 박복희
    • Proceedings of the SOHE Conference
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    • pp.39-43
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    • 1997
  • Toha-jeod was manufactured by seven methods ; low salt group (L:15% sodium chloride), high salt g group (H:23% sodium chloride), 50% conventional soybean sauce group (S), low salt group containing 2% w wheat bran (W2%-L), high saIt group containing 2% wheat bran (W2%-H),high salt group containing 2% wheat bran (W2%-H), high salt group containing 4% wheat bran (W4%-H). After these seven groups were refrigerated at $4{\pm}1^{\circ}C$, they were sampled at intervals of three months and analyzed functional components. The free amino acid in Toha-jeod which are omitine, glutamic acid, leucine, alanine, lysine and valine increased gradually up to six months of fermentation and decreased by nine months. Conventional soybean sauce group increased continuously during the fermentation process. Hypoxanthine was altered almost among other nueletides. ATP was not detected, IMP and inosine had disapapted after the six months fermentation. Polyene fatty acids and n-3 fatty acids were decreased and s saturated fatty acids were not altered in the group containing wheat bran during fermentation. In the Hunter values, the group containing wheat bran and high salt group showed lower level than the group n not containing wheat bran and low salt group. Redness indicating the value of Toha-jeod increased as Toha-jeod was fermentated. Low salt group and conventional soybean sauce group were superior to other groups in the extent of redness. As the fermentation of Toha-jeod progressed for a long time, molecular weight distribution tended to become less molecular and the formation of chitin oligosaccharides was increased significantly. After nine months of fermentation, 24.75% chitin oligosaccharides [($GlcNAd_4$ ~ ($GlcNAd_8$, M.W. 823~1789] were created in the high salt group containing 2% wheat bran. [($GlcNAd_6$. M.W. 1236J , that is NACOS-6, which was reported as an antitumor activity material, was present in 4.01~4.37% of total Toha chitin content. 66.30% chitin oligosaccharides were created in conventional soybean sauce.

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The Storage Stability of Semi-Salted and Dried Mackerel by Free-Oxygen Absorber (탈산소제에 의한 반염건고등어 저장중의 품질안정성)

  • LEE Eung-Ho;CHUNG Young-Hoon;JOO Dong-Sik;KIM Jeong-Hee;OH Kwang-Soo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.18 no.2
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    • pp.131-138
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    • 1985
  • The preservative effect of modified-atmosphere storage on the shelf-life of packed semi-salted and dried mackerel, Scomber japonicus, was examined. The semi-salted and dried mackerel fillets were packed in laminated plastic film bags (polyester/nylon/casted polypropylene: $12{\mu}m/15{\mu}m/60{\mu}m,\;15{\times}16cm$) filled with air (control, C), nitrogen gas (N), deoxygenized air (O) prepared by using free-oxygen absorber enclosed in the bag, in vacuum(V), and stored at $5^{\circ}C$. The quality of packed sample during the storage were examined in terms of viable cell counts of bacteria, thiobarbituric acid(TBA) value, perozide value(POV), volatile basic nitrogen(VBN), trimethylamine(TMA), adenosine triphosphate(ATP) and its related compounds and sensory evaluation. The results obtained are as follows: The pH of all the samples was in the range of $6.1{\pm}0.2$, and the contents of VBN and amino nitrogen of them increased during storage. In color values, L value(lightness) decreased while a and b values (red and yellow) revealed a tendency to increase during storage. The viable cell counts of the control sample(C) increased to $3.0{\times}10^6/g$ after 15 days storage but those of the other samples(V, N and O)were in the range of $2{\sim}6{\times}10^5/g$ after 20 days storage. The content of TMA increased during storage, but the histamine content showed a little change during storage and its content of all samples were less than 16 mg/100g. The inosinic acid(IMP) was rapidly degraded while inosine and hypoxanthine increased during storage. The TBA value of the control(C) reached a peak in 9 days and then decreased gradually while that of the sample(O) showed a little change during storage. The changes in POV of all the samples during storage showed a similar tendency to the TBA value. Fatty acid composition of raw mackerel consists of $35.6\%$ of saturated acid, $30.3\%$ of monoenoic acid and $34.2\%$ of polyenoic acid. The major fatty acid of the sample products were oleic acid($C_{18:1}$), palmitic acid($C_{16:0}$), docosahexaenoic acid($C_{22:6}$). The contents of polyenoic acid such as $C_{22:6},\;C_{20:5}$ decreased during storage while the other fatty acids showed a little change. From the results of sensory evaluation, the shelf-life of the control sample(C) was about 7 days and that of sample(V), (N) and (O) was about 15 days. It was concluded that deoxygenized atmosphere(free-oxygen absorber enclosed in the bag) was a good condition for preserving the quality of semi-salted and dried mackerel.

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Characteristics of Food Components in Granular Ark and Ark Shell (고막 및 새고막의 부위별 식품성분 특성)

  • Kim Kui Shik;Kim Jeung Hoon;Bae Tae Jin;Park Choon-Kyu;Kim Myung-Hee
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.35 no.5
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    • pp.512-518
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    • 2002
  • In order to effectively utilize of granular ark and ark shell, lipid and fatty acid compositions, free amino acids, nucleotides and their related compounds and minerals in the muscle and viscera of raw and cooked specimens were analyzed. The major constituents of non-polar lipids in the granular ark and ark shell were triglycerides, which showed higher content in viscera than the muscle. The polar lipids in the granular ark and ark shell were mainly consisted of phosphatidylcholine and phosphatidylethanolamine. The major fatty acids of total lipid were 16:0, 20:5n-3, 18:1n-9, 16:1n-7, 18:0 and 22:6n-3 both the granular ark and ark shell. The major nucleotides and the related compounds were adenosine monophosphate and adenosine diphosphate and they had higher content in the muscle than in viscera both samples, free amino acids such as taurine, glycine, alanine, glutamic acid, phenyl alanine and aspartic acid were abundant both the granular ark and ark shell. In the raw muscle of granular ark, glycine, alanine and $\alpha$-amino-iso-butyric acid were high level, but glutamic acid, aspartic acid and phenyl alanine were low level compared with those of cooking muscle. In the raw muscle of ark shell, taurine and $\alpha$-amino-iso-butyric acid were high content, but the glutamic acid and aspartic acid were low level compared with those of cooking muscle. Minerals in the granular ark and ark shell were chiefly consisted of potassium, sodium, magnesium, iron and calcium.

Effects of Low Level of Levan Feeding on Serum Lipids, Adiposity and UCP Expression in Rats (저농도 레반 공급이 혈중 지질 및 체지방 형성과 UCP 발현에 미치는 영향)

  • 강순아;홍경희;장기효;김소혜;조여원
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.31 no.5
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    • pp.788-795
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    • 2002
  • This study described the effect of levan (9-2,6-linked fructose polymer) feeding on serum lipids, adiposity and uncoupling protein (UCP) expression in growing rats. Levan was synthesized from sucrose using bacterial levansucrase. UCP is a mitochondrial protein that uncouples the respiratory chain from oxidative Phosphorylation and generates heat instead of ATP, thereby increase energy expenditure. We observed that 3% or 5% levan containing diet reduced serum triglyceride levels, visceral and peritoneal fat mass and induced the UCP expression in rats fed high fat diet in previous study. To determine whether the intake of low level of levan may have the hypolipidemic and anti-obesity effect, 4 wk old Sprague Dawley male rats were fed AIN-76A diet for 6 wk, and sub-sequently fed 1% or 2% levan solution for further 5 wk. Intake of 1% levan in liquid form reduced serum triglyceride and serum total cholesterol levels to 50% and 66% of control group, respectively. Although epididymal and peritoneal fat masses were not affected by levan feeding, visceral fat mass was lower in 1% levan group compared to control group. The expression of UCP2 mRNA in brown adipose tissue, skeletal muscle and hypothalamus and UCP3 mRNA in skeletal muscle were not changed by levan feeding, while the UCP2 mRNA in white adipose tissue was up-regulated by levan feeding. In conclusions, intake of low level of levan solution reduced serum triglyceride and total cholesterol, restrained the visceral fat accumulation and increased UCP expression in white adipose tissue in rats. This study suggests that hypolipidemic and anti-obesity effect of levan attributed to anti-lipogenesis and inefficeint energy utilization by up-regulation of UCPs.