• Journal of Microbiology and Biotechnology
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• 제8권6호
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• pp.705-709
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• 1998

In the course of screening for the substances suppressing bleb formation of K562 cell induced by phorbol 12, 13-dibutyrate (PDBu), an inhibitor, chaetoglobosin A (CgA) was isolated from a cultured broth of unidentified fungus. CgA showed a strong inhibitory activity with the $IC_{50}$ value of 60 pM against bleb formation on K562 cells induced by PDBu, but it did not inhibit the activity of protein kinase C (PKC) in vitro. The inhibitory activity of CgA might be due to the modulation of actin filaments on the cell membrane. CgA exhibited strong cytotoxicity against various human cancer cell lines.

• Genomics & Informatics
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• 제9권2호
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• pp.64-68
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• 2011

Monomelic amyotrophy (MA), also known as Hirayama disease, occurs mainly in young men and manifests as weakness and wasting of the muscles of the distal upper limbs. Here, we sought to identify a genetic basis for MA. Given the predominance of MA in males, we focused on candidate neurological disease genes located on the X chromosome, selecting two X-linked candidate genes, androgen receptor (AR ) and ubiquitin-like modifier activating enzyme 1 (UBA1). Screening for genetic variants using patients' genomic DNA revealed three known genetic variants in the coding region of the AR gene: one nonsynonymous single-nucleotide polymorphism (SNP; rs78686797) encoding Leu57Gln, and two variants of polymorphic trinucleotide repeat segments that encode polyglutamine (CAG repeat; rs5902610) and polyglycine (GGC repeat; rs3138869) tracts. Notably, the Leu57Gln polymorphism was found in two patients with MA from 24 MA patients, whereas no variants were found in 142 healthy male controls. However, the numbers of CAG and GGC repeats in the AR gene were within the normal range. These data suggest that the Leu57Gln polymorphism encoded by the X-linked AR gene may contribute to the development of MA.

• Animal cells and systems
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• 제15권4호
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• pp.301-309
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• 2011

Charcot-Marie-Tooth disease (CMT) is clinically heterogeneous hereditary motor and sensory neuropathies with genetic heterogeneity, age-dependent penetrance, and variable expressivity. Rare copy number variations by nonrecurrent rearrangements have recently been suggested to be associated with Charcot-Marie-Tooth 1A (CMT1A) neuropathy. In our previous study, we found three Korean CMT1A families with rare copy number variations (CNVs) on 17p12 by nonrecurrent rearrangement. Careful clinical examinations were performed in all the affected individuals with rare CNVs (n=19), which may be the first full study of a subject from a large CMT1A family with nonrecurrent rearrangement. The clinical phenotype showed no significant difference compared with common CMT1A patients, but with variable phenotypes. In particular, a broad intrafamilial phenotypic spectrum was observed within the same family, which may suggest the existence of a genetic modifier. This study may broaden the understanding of the role of CNVs in the pathogenesis of CMT.

• Journal of Plant Biology
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• 제36권2호
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• pp.127-132
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• 1993

Self-incompatibility in Brassica campestris is controlled by multi-allele system in a single genetic locus, the S locus, and it is elucidated that S-glycoproteins are S gene products. In this experiments, we examined the genetic mode(pollen tube behavior and segregation of S-glycoprotein), characteristic of S-glycoproteins and DNA constitution within nuclear genome on S gene family that unexplained by single locus model, and investigated the segregation pattern of S-glycoproteins in bred F1 generation. By diallel cross among the 15 plants within one family the existence of three types of homozygotes and three types of heterozygotes were observed, and segregation of S-allele could not explained by single locus model. From the results of IEF-immunoblot analysis for non-segregated individual plant, the segregation pattern of S specific bands was corresponded with results of diallel cross except with one case(SaSa genotype). The molecular weight of 6 different S-genotype varied in near by 50 kD, and each genotype expressed with 2 or 3 bands. Specific bands in SaSa, SbSb, ScSc has almost similar molecular weight between them. Southern analysis of genomic DNA probed with S-glycoprotein cDNA for 6 different genotypes revealed that there are clear difference in polymorphism, multiple bands of hybridization, when restriction enzymes of EcoR I were used. It could be assumed that there are several sequences related to the S-glycoprotein structural genes within their nuclear genome. Therefore, we suggested the possibilities that S-allele system could be controlled by multi-locus, that dominance-recessive interactions could be explained by modifier gene or supressor gene based on the results of abnormal segregation of S-glycoprotein in bred F1. The F2 analyses are progressing in now.

• BMB Reports
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• 제48권8호
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• pp.445-453
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• 2015

Endoplasmic Reticulum (ER) is an organelle where most secretory and membrane proteins are synthesized, folded, and undergo further maturation. As numerous conditions can perturb such ER function, eukaryotic cells are equipped with responsive signaling pathways, widely referred to as the Unfolded Protein Response (UPR). Chronic conditions of ER stress that cannot be fully resolved by UPR, or conditions that impair UPR signaling itself, are associated with many metabolic and degenerative diseases. In recent years, Drosophila has been actively employed to study such connections between UPR and disease. Notably, the UPR pathways are largely conserved between Drosophila and humans, and the mediating genes are essential for development in both organisms, indicating their requirement to resolve inherent stress. By now, many Drosophila mutations are known to impose stress in the ER, and a number of these appear similar to those that underlie human diseases. In addition, studies have employed the strategy of overexpressing human mutations in Drosophila tissues to perform genetic modifier screens. The fact that the basic UPR pathways are conserved, together with the availability of many human disease models in this organism, makes Drosophila a powerful tool for studying human disease mechanisms. [BMB Reports 2015; 48(8): 445-453]

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10387-10391
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• 2015

Background: This study aimed to identify any association between the p73 gene G4C14-to-A4T14 polymorphism and risk of non-small cell lung cancer (NSCLC) in the south of China. Materials and Methods: We genotyped the p73 gene polymorphism of peripheral blood DNA from 168 patients with NSCLC and 195 normal controls using HRM (high resolution melting) and PCR-CTPP (polymerase chain reaction with confronting two-pair primers). Results: The results of genotyping by HRM and PCR-CTPP were consistent with direct sequencing, the p73 genotype distribution in 168 lung cancer patients being as follows: GC/GC 101 cases (60.1%), GC/AT 59 cases (35.1%), AT/AT 8 cases (4.8%). The carriers of AT/AT genotype had a significantly reduced risk of NSCLC (OR=0.370; 95%CI: 0.170-0.806; p=0.010) as compared with non-carriers. However, we found no relations between p73 genotypes and histological type (p=0.798, $x^2=0.452$), tumor stage (p=0.806, $x^2=0.806$), or lymph node metastasis (p=0.578, $x^2=1.098$). Conclusions: Our findings suggest that the p73 G4C14-to-A4T14 polymorphism may be a modifier of NSCLC susceptibility in the Chinese population.

• Archives of Pharmacal Research
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• 제16권4호
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• pp.259-264
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• 1993

Three cell lines, CHO, L929 and B16 which are non-tumorigenic and cancer cells, respectively, were first tested for their survival in the presence of radioprotective ginseng protein fraction(GPF0. The influence of three radioprotectors-CPF, cysteamine, and 1-Methyl-2-bis[(2-methylthio)vinyl] quinolinium iodide (MVQI) on DNA repair capacity of UV damaged cells survival test, the GPF showed higher cytotoxicity in L929 and B16 than in CHO cells. However, the degree of cell killing was also investigated by measuring $^3H$-thymidine incorporation of PUVA treated cells. In cell survival test, the GPF showed higher cytotoxicity in L929 and B16 than in CHO cells. However, the degree of cell killing was not high enough to consider it as an antitumorigenic agent. Variable results were obtained in the effects on DNA repair capacity depending on the protectors and cell lines used. In pretreatment, the presence of GPF and MVOI brought about a sinificant increase in the capacity in both CHO and B16 cells. However, in L929, the enhancing effect was not shown. In all three cell lines, cysteamine showed lower repair capacity than control, suggesting the primary damage reduction in stronger enhancing effects in L929 and B16 cells, while it was weaker in CHO cells. Here also cystemine hsowed a very little or no increase in the capacity in all three cell lines. These results demonstrate that GPF has mild cytotoxicity in tumorignic cells and that GPF and MVQI enhance DNA repair capacity of UV damaged cells, whether they are tumorigenic or not. On the other hand, cysteamine shows only damage reduction effect. Celles of different genetic origin seem to give different responses to the modifier and different modifiers may possibly work by different mechanisms.

• 생명과학회지
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• 제29권7호
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• pp.800-808
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• 2019

샤르코-마리-투스병(Charcot-Marie-Tooth disease: CMT)은 희귀 말초신경병의 그룹으로, 진행성 근육 약화 및 위축, 감각 소실, 상지 및 하지의 무반사 증상을 나타낸다. CMT1A는 PMP22 유전자가 존재하는 17p12 지역의 직렬 중복으로 발병하는데, 유전자형-표현형의 상관성이 느슨하여 2차 유전적 요인의 존재를 암시한다. 최근 MIR149의 rs71428439 (n.83A>G)와 rs2292832 (n.86T>C) 변이가 후기 발병 및 가벼운 증상의 표현형과 연관성이 있는 것으로 보고되었다. 본 연구는 CMT1A 기계내 임상적 표현형의 이질성이 MIR149의 SNP과 연관성이 있는지를 규명하기 위해 수행하였으며, 조사 대상으로는 가계내 표현형의 차이가 심한 6 CMT1A 대 가계를 대상으로 하였다. 그 결과, MIR149의 rs71428439와 s2292832 유전자형은 가족내의 늦은 발병과 약한 중증도의 유전적 요인으로 작용할 수 있음을 제시하였다. 특히, AG+GG (n.83A>G)와 TC+CC 유전자형(n.86T>C)은 발병 시기가 늦고 경미한 증상을 보였다. 운동신경 전기전도도(MNCV)는 MIR149 유전형과 연관이 없는 것으로 보였는데, 이러한 결과는 이전 연구와 일치한다. 따라서 본 연구는 MIR149의 rs71428439와 rs2292832 변이는 CMT1A 가계내 표현형적 이질성의 원인 중 하나로 작용할 가능성을 제시한다. 본 연구는 가계 내 증상의 차이가 심한 6 대가족을 사용하여 연구를 수행한 것은 의미가 크다고 여겨지며, 이런 결과는 CMT1A 환자의 분자 진단과 치료에 도움을 줄 수 있을 것으로 기대된다.