• Title/Summary/Keyword: N-acetyltransferase

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Effect of Acupuncture at ST36 on Ischemia-induced Learning and Memory Deficits in Gerbils

  • Chung, Jin-Yong;Park, Hyun-Jung;Shim, Hyun-Soo;Hahm, Dae-Hyun;Kim, Hee-Young;Lee, Hye-Jung;Kim, Kyung-Soo;Shim, In-Sop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.2
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    • pp.300-305
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    • 2011
  • The present study was investigated the neuroprotective effects of acupuncture at ST36 on learning and memory deficits after transient cerebral ischemia in a gerbil model. The animals were randomly divided into three groups (n=7 in each group): the sham operation group (SHAM), ischemia-induced and ST36 acupuncture group (ISC + ST36), and the ischemia-induced and Tail-acupuncture group (ISC + TAIL). For the acupuncture stimulation, stainless steel needles, 0.3 mm in diameter, were inserted bilaterally into the ST36 locus or the tail and stimulated for 1 min/day for 14 days. Using the Morris water maze test, the animals were tested on spatial learning and memory. In addition, the effects of acupuncture on memory storage and the choline acetyltransferase (ChAT) activity, in the hippocampal CA1 area, were investigated by ChAT immunohistochemistry. Transient cerebral ischemia produced impaired performance on the MWM test (DAY 5: p<0.01 and retention test: p<0.05) and severely decreased ChAT immunoreactivity in the CA1 hippocampal area compared to the SHAM group (p<0.05). However, improved learning and memory were observed (DAY 5: p<0.05 and retention test: p<0.01) as well as a significantly reduced loss of ChAT immunoactivity in the hippocampal CA1 region (p<0.001) after acupuncture stimulation at ST36 were observed. These results show that acupuncture at ST36 ameliorated the learning and memory deficits at least in part through the cholinergic system. The findings of this study provide potential data that acupuncture is useful for the treatment of some of the behavioral impairs of transient cerebral ischemia.

Effects of Rice Bran Extracts Fermented with Lactobacillus plantarum on Neuroprotection and Cognitive Improvement in a Rat Model of Ischemic Brain Injury

  • Hong, Jeong Hwa;Kim, Ji Yeong;Baek, Seung Eun;Ingkasupart, Pajaree;Park, Hwa Jin;Kang, Sung Goo
    • Biomedical Science Letters
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    • v.21 no.2
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    • pp.92-102
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    • 2015
  • This work aimed to study whether rice bran extract fermented with Lactobacillus plantarum (LW) promotes functional recovery and reduces cognitive impairment after ischemic brain injury. Ischemic brain injury was induced by middle cerebral artery occlusion (MCAO) in rats. Four groups were studied, namely the (1) sham, (2) vehicle, (3) donepezil, and (4) LW groups. Animals were injected with LW once a day for 7 days after middle cerebral artery occlusion. LW group showed significantly improved neurological function as compared to the vehicle group, as well as enhanced learning and memory in the Morris water maze. The LW group showed the greatest functional recovery. Moreover, the LW group showed an enhanced more survival cells anti-apoptotic effect in the cortex and neural cell densities in the hippocampal DG and CA1. In addition, this group showed enhanced expression of neurotrophic factors, antioxidant genes, and the acetylcholine receptor gene, as well as synaptophysin (SYP), Fox-3 (NeuN), doublecortin (DCX), and choline acetyltransferase (ChAT) proteins. Our findings indicate that LW treatment showed the largest effects in functional recovery and cognitive improvement after ischemic brain injury through stimulation of the acetylcholine receptor, antioxidant genes, neurotrophic factors, and expression of NeuN, SYP, DCX, and ChAT.

Endotoxin-induced inflammation disturbs melatonin secretion in ewe

  • Herman, Andrzej Przemyslaw;Wojtulewicz, Karolina;Bochenek, Joanna;Krawczynska, Agata;Antushevich, Hanna;Pawlina, Bartosz;Zielinska-Gorska, Marlena;Herman, Anna;Romanowicz, Katarzyna;Tomaszewska-Zaremba, Dorota
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.12
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    • pp.1784-1795
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    • 2017
  • Objective: The study examined the effect of intravenous administration of bacterial endotoxin-lipopolysaccharide (LPS) -on the nocturnal secretion of melatonin and on the expression of enzymes of the melatonin biosynthetic pathway in the pineal gland of ewes, taking into account two different photoperiodic conditions: short-night (SN; n = 12) and long-night (LN; n = 12). Methods: In both experiments, animals (n = 12) were randomly divided into two groups: control (n = 6) and LPS-treated (n = 6) one. Two hours after sunset, animals received an injection of LPS or saline. Blood samples were collected starting one hour after sunset and continuing for 3 hours after the treatment. The ewes were euthanized 3 hours after LPS/saline treatment. The concentration of hormones in plasma was assayed by radioimmunoassay. In the pineal gland, the content of serotonin and its metabolite was determined by HPLC; whereas the expression of examined genes and protein was assayed using real-time polymerase chain reaction and Western Blot, respectively. Results: Endotoxin administration lowered (p<0.05) levels of circulating melatonin in animals from LN photoperiod only during the first hour after treatment, while in ewes from SN photoperiod only in the third hour after the injection. Inflammation more substantially suppressed biosynthesis of melatonin in ewes from SN photoperiod, which were also characterised by lower (p<0.05) cortisol concentrations after LPS treatment compared with animals from LN photoperiod. In the pineal gland of ewes subjected to SN photoperiod, LPS reduced (p<0.05) serotonin content and the expression of melatonin biosynthetic pathway enzymes, such as tryptophan hydroxylase and arylalkylamine-N-acetyltransferase. Pineal activity may be disturbed by circulating LPS and proinflammatory cytokines because the expression of mRNAs encoding their corresponding receptors was determined in this gland. Conclusion: The present study showed that peripheral inflammation reduces the secretion of melatonin, but this effect may be influenced by the photoperiod.

Classification of HDAC8 Inhibitors and Non-Inhibitors Using Support Vector Machines

  • Cao, Guang Ping;Thangapandian, Sundarapandian;John, Shalini;Lee, Keun-Woo
    • Interdisciplinary Bio Central
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    • v.4 no.1
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    • pp.2.1-2.7
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    • 2012
  • Introduction: Histone deacetylases (HDAC) are a class of enzymes that remove acetyl groups from ${\varepsilon}$-N-acetyl lysine amino acids of histone proteins. Their action is opposite to that of histone acetyltransferase that adds acetyl groups to these lysines. Only few HDAC inhibitors are approved and used as anti-cancer therapeutics. Thus, discovery of new and potential HDAC inhibitors are necessary in the effective treatment of cancer. Materials and Methods: This study proposed a method using support vector machine (SVM) to classify HDAC8 inhibitors and non-inhibitors in early-phase virtual compound filtering and screening. The 100 experimentally known HDAC8 inhibitors including 52 inhibitors and 48 non-inhibitors were used in this study. A set of molecular descriptors was calculated for all compounds in the dataset using ADRIANA. Code of Molecular Networks. Different kernel functions available from SVM Tools of free support vector machine software and training and test sets of varying size were used in model generation and validation. Results and Conclusion: The best model obtained using kernel functions has shown 75% of accuracy on test set prediction. The other models have also displayed good prediction over the test set compounds. The results of this study can be used as simple and effective filters in the drug discovery process.

Effects of the Genetic Polymorphisms on Urinary Excretion of 1-Hydroxypyrene and 2-Naphthol (일반인구에서 유전자 다형성이 요중 1-hydroxypyrene 및 2-naphthol의 배설량에 미치는 영향)

  • Hwang Moon-Young;Cho Byung-Mann;Moon Seong-Bae
    • Journal of Environmental Science International
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    • v.14 no.5
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    • pp.499-511
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    • 2005
  • This study was performed to determine the effects of genetic polymorphisms, such as glutathione S-transferase ${\mu}1(GSTM1)$, glutathione S-transferase ${\Theta}1\;(GSTM1)$, glutathione S-transferase ${\pi}l (GSTP1)$, aryl hydrocarbon N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), cytochrome P450 1A1 (CYP1A1) on the concentrations of urinary 1-hydroxypyrene (1-OHP) and 2-naphthol in general population with no occupational exposure to polycyclic aromatic hydrocarbons (PAHs). Study subjects were 257 men who visited a health promotion center in Susan. A questionnaire was used to obtain detailed data about age, smoking, drinking, body fat mass, intake of fat etc. Urinary l-OHP and 2-naphthol concentration were analyzed by HPLC system with a fluorescence detector. A multiplex PCR method was used to identify the genotypes for GSTM1 and GSTT1. The polymorphisms of GSTP1, NAT2, CYP1A1 and CYP2E1 were determined by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Urinary 1-OHP concentration was higher in deleted genotype of GSTM1, increased as smoking and alcohol drinking increased. Urinary 2-naphthol concentration was also rely on the age and smoking. Neither genetic polymorphism nor drinking-related factors were significantly related to urinary 2-naphthol concentration. No significant relation was found between physical characteristics and concentrations of urinary PAHs metabolites in the subjects, but the geometric mean of urinary 1-OHP and 2-naphthol was higher in the group with higher value compared to median value. These data suggest that in general population occupationally not exposed to PAHs, urinary concentration of PAHs metabolites is influenced by smoking, alcohol drinking and deleted genotype of GSTM1 in 1-OHP and smoking in 2-naphthol.

Identification of DC21 as a Novel Target Gene Counter-regulated by IL-12 and IL-4

  • Kong, Kyoung-Ah;Jang, Ji-Young;Lee, Choong-Eun
    • BMB Reports
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    • v.35 no.6
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    • pp.623-628
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    • 2002
  • The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.

Effects of Silkworm(Bombyx mori L..) Powder on Lipofuscin, Acetylcholine and Its Related Enzyme Activities in Brain of Rats (뇌조직의 리포푸신, 아세틸콜린 및 그 관련효소 활성에 미치는 누에분말의 영향)

  • 최진호;김대익;박수현;김정민;조원기;이희삼;류강선
    • Journal of Life Science
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    • v.10 no.6
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    • pp.564-569
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    • 2000
  • This study was designed to investigate the effect of silkworm (Bombyx mori L.) powder on lipofuscin, acetylcholine (ACh) and its related enzyme activities in brain of rats. Sprague-Dawley (SD) male rats ($160{\pm}10g$) were fed basic diet (control group), and experimental diets (SWP-200 and SWP-400 groups) added 200 and 400 mg/kg BW/day for 6 weeks. In case of liver membranes, lipofuscin (LF) levels resulted in a slight decreases (4.6% and 11.5%, respectively) in SWP-200 and SWP-400 groups compared with control group. But in case of barin as the most sensitive organ, LF levels were remarkably inhibited about 16.7% and 20.0% in SWP-200 and SWP-400 groups compared with control group. There were no significant differences in acetylcholine (ACh) syntheses as a very important neurotransmitter, and choline acetyltransferase (ChAT) activities as a synthesis enzyme of ACh, and acetylcholinesterase (AChE) activities as a hydrolysis enzyme, which were concerned in transmission of neuron through synapses in brain of SWP-200 and SWP-400 groups compared with control group. Monoamine oxidase-B (MAO-B) activities were significantly inhibited (about 10.2%) in brain of SWP-400 groups compared with control group. These results suggest that inhibiting effects of LF accumulation and MAO-B activity of silkworm powder (SWP) may play a pivotal role in attenuating a various age-related changes for improvement of brain function.

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Anti-apoptotic and Neuroprotective Effects of Acupuncture at $LR_3$ on Focal Brain Ischemic Injury Induced by Intraluminal Filament Insertion in Rats (다종(多種)의 태충(太衝)($LR_3$) 침척요법(鍼刺療法)이 Intraluminal Filament 삽입술로 유발된 백서(白鼠)의 허혈성 국소 뇌손상에 미치는 영향)

  • Yim, Hyun-Jin;Cho, Myung-Rae;Youn, Dae-Hwan;Na, Chang-Su;Ryu, Chung-Ryeol
    • Journal of Acupuncture Research
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    • v.24 no.2
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    • pp.125-140
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    • 2007
  • Objectives: This study was performed to investigate the effects of acupuncture therapy(AT, AT-9), electro-acupuncture therapy(EAT) and low level laser acupuncture therapy(LAT) at LRJ on the focal ischemia-induced by intraluminal filament insertion in rats. Methods : In the present syudy, the focal ischemia was induced by Intraluminal filament insertion into left middle cerebral artery. The subjects were divided into five groups after focal brain ischemia. (n=15, in each group) : Control with no treatment, AT with acupuncture at $LR_3$, AT-9 with acupuncture at $LR_3$ and rotating 9 times in a clockwise direction, EAT with electro-acupuncture at $LR_3$ and LAT with invasive laser acupuncture at $LR_3$. Anti-apoptotic and neuroprotective effects of acupuncture were observed by mGluR5 mRNA, Bax mRNA, Bcl-2 mRNA, Cytochrome C protein, Cresyl violet-stain and Choline acetyltransferase (ChAT)-stain in the hippocampus. Results: 1. In LAT, mGluR5, Cresyl violet-stain and ChAT-stain were increased. 2. In LAT, Cytochrome C protein was decreased. 3. In AT-9, Bax, Cytochrome C protein and the Bax/Bcl-2 ratio were decreased. 4. In AT-9, Bcl-2, Cresyl violet-stain and ChAT-stain were increased. 5. In EAT, Bcl-2 and Cresyl violet-stain were increased. Conclusions: These results suggests that LAT and AT-9 show anti-apoptotic and neuro-protective effects and that LAT and AT-9 may be useful for managing stroke by focal brain ischemia.

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Enhanced Production of Albumin-erythropoietin by Histone Deacetylase Inhibitors in Recombinant CHO Cells (유전자재조합 CHO 세포에서 Histone Deacetylase Inhibitor를 이용한Albumin-erythropoietin 생산성 증진)

  • Kim, Su-Jin;Seo, Joon-Serk;Choi, Sung-Hun;Cha, Hyun-Myoung;Lim, Jin-Hyuk;Shin, Soo-Ah;Shin, Yeon-Kyeong;Kim, Dong-Il
    • KSBB Journal
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    • v.30 no.1
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    • pp.44-51
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    • 2015
  • Chinese hamster ovary (CHO) cells are the most widely used mammalian host for the commercial production of recombinant proteins. However, they show relatively low yields of recombinant proteins in comparison with microbial cells. Various strategies have been tried to overcome this drawback. The acetyl moieties are attached to the N-terminus of histone by histone acetyltransferase (HAT) while histone deacetylase (HDAC) removes histone-bound acetyl groups. HDAC inhibitor (HDACi), such as sodium butyrate, sodium propionate and valproic acid, can enhance specific productivity of CHO cells. Human albumin-erythropoietin (Alb-EPO) is a novel 105 kDa protein comprising recombinant human EPO fused to human albumin. In this study, we examined the effects of HDACi on the production of Alb-EPO in CHO cells with various concentrations in the range of 0-1 mM. The results showed that sodium butyrate was found to be the best HDACi for enhancing productivity. It enhanced not only the production of Alb-EPO but also the apoptosis of recombinant CHO cells.