• 제목/요약/키워드: O-methyltransferase gene

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Sensitive and Noninvasive Detection of Aberrant SFRP2 and MGMT-B Methylation in Iranian Patients with Colon Polyps

  • Naini, M Alizade;Mokarram, P;Kavousipour, S;Zare, N;Atapour, A;Zarin, M Hassan;Mehrabani, G;Borji, M
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권4호
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    • pp.2185-2193
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    • 2016
  • Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.

ASSOCIATION BETWEEN TOURETTE DISORDER AND CATECHOL-O-METHYL TRANSFERASE(COMT) GENE IN KOREAN SUBJECTS (한국인에 있어서의 뚜렛 장애와 COMT유전자간의 상관 관계에 대한 연구)

  • Kim, Boong-Nyun;Lim, Jae-In;Cho, Soo-Churl
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • 제15권2호
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    • pp.178-184
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    • 2004
  • Objectives : This study was conducted to investigate the association of the COMT polymorphism with the TD in Korean sample of families with TD probands. The relationship between risk alleles and specific clinical features (tic severity, comorbidity, drug response) was also explored. Method : Patients were recruited from the Tic Disorder clinic at the Child & Adolescent Psychiatric Division of Seoul National University Hospital and assessed through 2 stage evaluation. Firstly, all the patients and parents received semistructured interview using Korean version of K-SADS-PL. Secondly all the patients received clinical interview and tic severity assessment with Korean version of YGTSS. The subjects in control group were recruited from the health promotion center in out hospital and were evaluated by SCL-90 and SCID-IV. Through these process, total of 42 children and adolescents with TD, their 84 parents and 86 control subjects were finally recruited. Genotyping for The Val158Met polymorphism of the COMT gene was done by standardized method. After collection of genetic data of all the patients, parents and control subjects, case-control comparison and tranmission dysequilibrium test was executed by SPSS version 11. Result : From the case-control comparison, the frequency of L-allele and LL genotype was significantly higher in TD group. However, no differences were found from the TDT. No significant differences were found in in family history of tic, ADHD, OCD, drug response and comorbid conditions among the three different genotypes in patients with TD. Conclusion : Though this study results should be interpreted cautiously due to small sample size and negative finding in TDT test, this study is the first report that there is positive association between the functional polymorphism of COMT gene the TD.

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Effect of Moutan Cortex Radicis on gene expression profile of differentiated PC12 rat cells oxidative-stressed with hydrogen peroxide (모단피의 PC12 cell 산화억제 효과 및 neuronal 유전자 발현 profile 분석에 대한 연구)

  • Kim Hyun Hee;Rho Sam Woong;Na Youn Gin;Bae Hyun Su;Shin Min Kyu;Kim Chung Suk;Hong Moo Chang
    • Journal of Physiology & Pathology in Korean Medicine
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    • 제17권2호
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    • pp.529-541
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    • 2003
  • Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

Molecular characterization of juvenile hormone signaling pathway-related genes in the brackish water flea Diaphanosoma celebensis (기수산 물벼룩의 유충 호르몬(Juvenile hormone) 신호전달경로 관련 유전자의 특성 분석)

  • Hayoung Cho;Jewon Yoo;Young-Mi Lee
    • Korean Journal of Environmental Biology
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    • 제40권3호
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    • pp.255-266
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    • 2022
  • In crustaceans, molting is regulated by interactions between ecdysteroid and juvenile hormone (JH) signaling pathway-related genes. Unlike the ecdysteroid signaling pathway, little information on the role of JH signaling pathway-related genes in molting is available in zooplanktonic crustaceans. In this study, three genes (juvenile hormone acid O-methyltransferase (JHAMT), methoprene-tolerant (Met), and juvenile hormone epoxide hydrolase (JHEH)) which are involved in the synthesis, receptor-binding, and degradation of JH were identified using sequence and phylogenetic analysis in the brackish water flea, Diaphanosoma celebensis. Transcriptional changes in these genes during the molting cycle in D. celebensis were analyzed. Sequence and phylogenetic analysis revealed that these putative proteins may be functionally conserved along with those of insects and other crustaceans. In addition, the expression of the three genes was correlated with the molting cycle of D. celebensis, indicating that these genes may be involved in the synthesis and degradation of JH, resulting in normal molting. This study will provide information for a better understanding of the role of JH signaling pathway-related genes during the molting process in Cladocera.