• Biomolecules & Therapeutics
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• 제22권4호
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• pp.275-281
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• 2014

Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophagosome marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium ($MPP^+$) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.

• Molecules and Cells
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• 제40권11호
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• pp.823-827
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• 2017

Genome editing using programmable nucleases such as CRISPR/Cas9 or Cpf1 has emerged as powerful tools for gene knock-out or knock-in in various organisms. While most genetic diseases are caused by point mutations, these genome-editing approaches are inefficient in inducing single-nucleotide substitutions. Recently, Cas9-linked cytidine deaminases, named base editors (BEs), have been shown to convert cytidine to uridine efficiently, leading to targeted single-base pair substitutions in human cells and organisms. Here, we first report on the generation of Xenopus laevis mutants with targeted single-base pair substitutions using this RNA-guided programmable deaminase. Injection of base editor 3 (BE3) ribonucleoprotein targeting the tyrosinase (tyr) gene in early embryos can induce site-specific base conversions with the rates of up to 20.5%, resulting in oculocutaneous albinism phenotypes without off-target mutations. We further test this base-editing system by targeting the tp53 gene with the result that the expected single-base pair substitutions are observed at the target site. Collectively, these data establish that the programmable deaminases are efficient tools for creating targeted point mutations for human disease modeling in Xenopus.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5191-5197
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• 2015

A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

• 대한임상검사과학회지
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• 제40권1호
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• pp.41-47
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• 2008

Colorectal carcinoma is occurred frequently to Korean and so ranked the fourth from various cancers. Due to western dietary life, this cancer has been increased continually. Therefore, the study will be needed to find a candidate gene involved in the development and progression of colorectal carcinoma and to diagnose and treatment helpfully. The striking feature from cancer suppressor genes is known for LOH (loss of heterozygosity), which is the method to find allele genetic loss or mutation of cancer cell. The purpose of this study was designed to find a carcinogenic gene from colon cancer using microsatellite marker on 17th and 18th chromosome from 30 subjects. The LOH was investigated in order of D18S59 57% (17/30), TP53CA 50% (15/30), D18S68 47% (14/30), D18S69 43% (13/30). The genetic mutation depends on loci of colorectal carcinoma was shown higher with 2.44 from colon cancer than with 1.25 from right colorectal carcinoma (p<0.032). The genetic mutation with lymph nodes was investigated higher with 2.69 at mutated group than with 1.14 at non-mutated group (p<0.003). At genetic mutated pattern depends on disease stage, there was higher significant difference at III-IV stage 2.50 than that of I-II stage 1.17, respectively (p=0.015). There was no difference at comparison between histological classification and serological CEA increase. The loss on 18q21 found in this study is highly recurrence loci and was observed 43% for Korean with high recurrence. Therefore, LOH is a very useful tool to detect 18q21 loci in clinical application, prior to the treatment of colorectal carcinoma. After the operation of colorectol carcinoma, the efficient application using LOH at operated part tissue which is designed to protect the recurrence as well as its cure will be needed.

• 한국작물학회지
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• 제53권3호
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• pp.285-291
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• 2008

This study was performed to find out starch properties of rice grains in three varieties with different amylose content, Ilpumbyeo (non-waxy), Goami2 (high amylose), and Hwasunchalbyeo (waxy rice). There was no difference among physico-chemical characteristics of rice grains, but Goami 2 showed $2{\sim}3$ folds higher crude fat (1.36%) than Ilpumbyeo. Pasting properties of RVA showed the highest values of maximum viscosity, breakdown, and final viscosity in Ilpumbyeo. A similar chain length distribution of amylopectin was found in Ilpumbyeo and Hwasunchalbyeo, indicating that DP 12 had the highest distribution. Goami 2 had the highest distribution in DP 14, and showed the lower percent (14.1%) than other rice cultivars. Thermal properties of DSC showed that the values of Tc and Tp of Hwasunchalbyeo were similar to Ilpumbyeo, whereas a slightly higher Tc was observed. The absorbtion enthalpy was also the highest (11.1 mJ/mg) in Hwasunchalbyeo. Goami 2 showed higher To, but the lowest enthalpy (6.52 mJ/mg) compared to Ilpumbyeo (7.92 mJ/mg). Retrogradation properties, which were measured with the gelatinized rice sample used for DSC, and stored in $4^{\circ}C$ during 6 days, indicated that retrogradation absorbtion peak was the first peak at $52.6{\sim}55.2^{\circ}C$, and the second peak above $95^{\circ}C$. Retrogradation enthalpy of Goami 2 was the highest value (5.12 mJ/mg).

• 한국동물학회지
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• 제33권1호
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• pp.53-62
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• 1990

양서류의 여포난자를 생체외에서 배양하면서 호르몬을 처리하면 난자의 성숙(핵붕괴)을 일으킨다. 본 연구는 북방산개구리의 여포난자를 배양하면서 난자내 단백질 분해효소들의 활성변화를 유도하여 이것이 난자의 성숙에 어떠한 영향을 미치는가를 조사하였다. chymotrypsin의 저해제로 알려진 N$\alpha$ -tosyl-L-phenylalanine-chloromethyl-ketone(TPCK)을 배양액에 처리하면 비교적 낮은 농도(0.001-1 $\mu$M)에서는 호르몬의 도움없이도 난자의 성숙을 유도하나 높은 농도 (100 $\mu$M)에서는 호르몬에 의한 난자의 성숙까지도 억제하는 이중적인 효과를 나타내었다. Trypsin의 저해제인 N$\alpha$ -tosyl-L-phenylalanine-chloromethyl-ketone(TPCK)은 성숙유도능력이 없을 뿐 아니라 progesterone에 의한 난자의 성숙을 억제하였다. Trypsin을 직접 처리했을 때에는 농도에 의존하여(0.001-1$\mu$g/2ml) 호르몬의 도움없이도 난자의 성숙을 유도함을 발견하였다. TLCK나 TPCK의 억제효과는 성숙 초기에만 나타났다. 본 결과는 양서류 난자의 성숙조절 과정에 몇종의 단백질 분해효소들이 참여한다는 것을 시사해주고 있다.

• Genomics & Informatics
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• 제11권4호
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• pp.239-244
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• 2013

Somatic mutation is a major cause of cancer progression and varied responses of tumors against anticancer agents. Thus, we must obtain and characterize genome-wide mutational profiles in individual cancer subtypes. The Cancer Genome Atlas database includes large amounts of sequencing and omics data generated from diverse human cancer tissues. In the present study, we integrated and analyzed the exome sequencing data from ~3,000 tissue samples and summarized the major mutant genes in each of the diverse cancer subtypes and stages. Mutations were observed in most human genes (~23,000 genes) with low frequency from an analysis of 11 major cancer subtypes. The majority of tissue samples harbored 20-80 different mutant genes, on average. Lung cancer samples showed a greater number of mutations in diverse genes than other cancer subtypes. Only a few genes were mutated with over 5% frequency in tissue samples. Interestingly, mutation frequency was generally similar between non-metastatic and metastastic samples in most cancer subtypes. Among the 12 major mutations, the TP53, USH2A, TTN, and MUC16 genes were found to be frequent in most cancer types, while BRAF, FRG1B, PBRM1, and VHL showed lineage-specific mutation patterns. The present study provides a useful resource to understand the broad spectrum of mutation frequencies in various cancer types.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.7.1-7.12
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• 2018

Recent findings from The Cancer Genome Atlas project have provided a comprehensive map of genomic alterations that occur in hepatocellular carcinoma (HCC), including unexpected mutations in apolipoprotein B (APOB). We aimed to determine the clinical significance of this non-oncogenetic mutation in HCC. An Apob gene signature was derived from genes that differed between control mice and mice treated with siRNA specific for Apob (1.5-fold difference; P < 0.005). Human gene expression data were collected from four independent HCC cohorts (n = 941). A prediction model was constructed using Bayesian compound covariate prediction, and the robustness of the APOB gene signature was validated in HCC cohorts. The correlation of the APOB signature with previously validated gene signatures was performed, and network analysis was conducted using ingenuity pathway analysis. APOB inactivation was associated with poor prognosis when the APOB gene signature was applied in all human HCC cohorts. Poor prognosis with APOB inactivation was consistently observed through cross-validation with previously reported gene signatures (NCIP A, HS, high-recurrence SNUR, and high RS subtypes). Knowledge-based gene network analysis using genes that differed between low-APOB and high-APOB groups in all four cohorts revealed that low-APOB activity was associated with upregulation of oncogenic and metastatic regulators, such as HGF, MTIF, ERBB2, FOXM1, and CD44, and inhibition of tumor suppressors, such as TP53 and PTEN. In conclusion, APOB inactivation is associated with poor outcome in patients with HCC, and APOB may play a role in regulating multiple genes involved in HCC development.

• 한국환경교육학회지:환경교육
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• 제11권1호
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• pp.151-164
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• 1998

Conclusion and the improvement plan according to the survey on recycling wastes in 'the program of woman and environmental education' mainly for the chairwomen of the women's association of the apartment house in City and County of Chungchongnamdo during the first half of 1998 (from March tp April) are as follows. 1. Conclusion 1) It showed that the rate of recognition for recycle has no difference by regional groups and the rate of recognition is 57.4% but they mainly know vaguely or they do not know. 2) It showed that the rate they do not know how the separated wastes are recycled is 30.4% and the scope of their knowledge is approximative.(52.6%) 3) It showed that it is the housewives who mainly do the separate garbage collection (72.7%) and 19.1% of the people have no interest in the separate discharge. 4) It showed that the rate they filter the garbage or remove water from the garbage at house is 53.1%. And 20% of the people in the urban region dump untreated wastes but 8.5% of the people in the rural region do the same, so the rate of using garbage in the rural region is higher than that in the urban region. 5) It showed that the separate state of the garbage is 29.2% for the removal of toothpick and paper and 47.4% for the removal of vinyl and stopper. 6) It showed that 66.7% of the motive for recycling waste is the education activity for environment by the women's association and SAEMAEUL association and 34.5% of that is the influence of TV and radio. 7) It showed that the rate of making compost and feed using garbage in the rural region is higher than that in the urban region and in some urban regions, the rate they sprinkle the garbage in provisional compost state on the floor garden is high. 8) It showed that the recognition rate for the material of separately collected garbage corresponding to the separate waste system of 5-6 classification is 12.5% 9) It showed that the major variable which has an effect on the recycle is the education activity for environment by the neighborhood meeting(P<0.05) and by the women's association of saemaeul activity(P<0.05)

• 사학연금연구
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• 제5권
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• pp.53-95
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• 2020

정부에서는 공적연금 운용 업무를 수행하는 연금공단에 대해서 지방세특례제한법상 조세감면 혜택을 부여해 왔으나, 2014년도부터는 지방자치단체의 재정확충을 위해서 지방세 특례를 폐지하였다. 이러한 지방세 특례 폐지가 연금재정에 부정적인 영향을 미치게 됨에 따라, 본 연구에서는 현행 사학연금공단에 대한 지방세 감면 폐지의 문제점를 살펴보고, 이를 통해 법 개정 등의 개선방안을 모색하고자 하였다. 구체적으로 2014년 말에 시행된 지방세 감면 규정의 일괄적인 폐지는 2002년에 개정된 연금소득 과세원칙에 비추어볼 때 과세원칙 위배와 함께 미적립 연금충당부채를 지니고 있는 연금공단의 제도적인 특성을 감안하지 않는 문제점이 있어 이를 검토하고 이에 대한 개선방안을 다음과 같이 제시하고자 한다. 본 연구에서 제시하는 개선방안은 다음과 같다. 첫째, 과거와 같이 사학연금공단에 대한 지방세특례를 부활하여 연금재정의 안정화를 제고할 필요가 있다. 둘째, 연금소득 원칙상 갹출 시 공제, 운용 시 비과세 및 연금 수령 시 과세를 하도록 하고 있으므로 현행 연기금을 운용하고 있는 사학연금공단에 대하여 운용단계에서 지방세를 부과하는 것은 연금소득 과세 원칙상 재검토가 필요하다. 셋째, 현재 연금기금의 운용이익에 대해서는 법인세가 비과세되으나 지방세는 과세가 되고 있어 국세와 지방세의 형평성 측면에서 문제가 있으므로 원칙적인 검토가 필요하다. 넷째, 미적립 연금충당부채를 지니고 있는 연금공단의 성격을 고려하여 현행 지방세의 부과는 연금공단의 기관 특성을 고려하지 않은 것으로 보여진다. 마지막으로, 가장 공적인 업무를 수행하고 있는 기관임에도 불구하고 타 비영리법인에서는 아직도 지방세특례가 존재하고 있는 실정이다. 따라서 사학연금공단은 공적인 업무를 수행하는 기관임에도 불구하고 지방세 특례가 폐지되었으므로 이에 대한 지원이 필요하다. 본 연구는 사학연금공단의 연금재정 안정화와 함께 과세원칙에 부합하도록 운용단계에서 반드시 필요한 연금관리 조직의 지방세 특례 부여 방안을 모색함으로써 사학연금공단의 지방세 지원의 타당성과 개선방안을 제시했다는 점에서 연구의 의의가 있다.