• Molecules and Cells
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• 제27권1호
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• pp.113-118
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• 2009

In this study, we have shown the transcriptional regulation of the human GD3 synthase (hST8Sia I) induced by valproic acid (VPA) in human neuroblastoma SK-N-BE(2)-C cells. To elucidate the mechanism underlying the regulation of hST8Sia I gene expression in VPA-stimulated SK-N-BE(2)-C cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5'-flanking region of the hST8Sia I gene by the transient expression method showed that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-${\kappa}B$, functions as the VPA-inducible promoter of hST8Sia I in SK-N-BE(2)-C cells. Site-directed mutagenesis and electrophoretic mobility shift assay indicated that the NF-${\kappa}B$ binding site at -731 to -722 was crucial for the VPA-induced expression of hST8Sia I in SK-N-BE(2)-C cells. In addition, the transcriptional activity of hST8Sia I induced by VPA in SK-N-BE(2)-C cells was strongly inhibited by SP600125, which is a c-Jun N-terminal kinase (JNK) inhibitor, and $G{\ddot{O}}6976$, which is a protein kinase C (PKC) inhibitor, as determined by RT-PCR (reverse transcription-polymerase chain reaction) and luciferase assays. These results suggest that VPA markedly modulated transcriptional regulation of hST8Sia I gene expression through PKC/JNK signal pathways in SK-N-BE(2)-C cells.

• Asian-Australasian Journal of Animal Sciences
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• 제33권2호
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• pp.187-196
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• 2020

Objective: Porcine respiratory disease is one of the most important health problems causing significant economic losses. To understand the genetic basis for susceptibility to swine enzootic pneumonia (EP) in pigs, we detected 102,809 single nucleotide polymorphisms in a total of 249 individuals based on genome-wide sequencing data. Methods: Genome comparison of susceptibility to swine EP in three pig breeds (Jinhua, Erhualian, and Meishan) with two western lines that are considered more resistant (Duroc and Landrace) using cross-population extended haplotype homozygosity and F-statistic (F_ST) statistical approaches identified 691 positively selected genes. Based on quantitative trait loci, gene ontology terms and literature search, we selected 14 candidate genes that have convincible biological functions associated with swine EP or human asthma. Results: Most of these genes were tested by several methods including transcription analysis and candidate genes association study. Among these genes: cytochrome P450 1A1 and catenin beta 1 (CTNNB1) are involved in fertility; transforming growth factor beta receptor 3 plays a role in meat quality traits; Wnt family member 2, CTNNB1 and transcription factor 7 take part in adipogenesis and fat deposition simultaneously; plasminogen activator, urokinase receptor (completely linked to AXL receptor tyrosine kinase, r² = 1) plays an essential role in the successful ovulation of matured oocytes in pigs; colipase like 2 (strongly linked to SAM pointed domain containing ETS transcription factor, r² = 0.848) is involved in male fertility. Conclusion: These adverse genes susceptible to swine EP may be selected while selecting for economic traits (especially reproduction traits) due to pleiotropic and hitchhiking effect of linked genes. Our study provided a completely new point of view to understand the genetic basis for susceptibility or resistance to swine EP in pigs thereby, provides insight for designing sustainable breed selection programs. Finally, the candidate genes are crucial due to their potential roles in respiratory diseases in a large number of species, including human.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1163-1168
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• 2016

Cholangiocarcinoma (CCA) is the bile duct cancer which constitutes one of the important public health problems in Thailand with high mortality rate, especially in the Opisthorchis viverrini (a parasite risk factor for CCA) endemic area of the northeastern region of the country. This study aimed to identify potential biomarkers from the plasma peptidome by CCA patients. Peptides were isolated using 10 kDa cut-off filter column and the flow-through was then used as a peptidome for LC-MS/MS analysis. A total of 209 peptides were obtained. Among these, 15 peptides were concerned with signaling pathways and 12 related to metabolic, regulatory, and biosynthesis of secondary metabolite pathways. Five exclusive peptides were identified as potential biomarkers, i.e. ETS domain-containing transcription factor ERF (P50548), KIAA0220 (Q92617), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 (P42338), LP2209 (Q6XYC0), and casein kinase II subunit alpha (P19784). Three of these biomarkers are signaling related molecules. A combination of these biomarkers for CCA diagnosis is proposed.

• 생명과학회지
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• 제20권5호
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• pp.655-661
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• 2010

흑색종세포주 SK-MEL-2에서 레티노이드에 의한 GD3합성효소(hST8Sia I)의 발현억제기작을 규명하게 위하여 hST8Sia I의 프로모터 활성을 조사해 본 결과 -1146에서 -646영역에서 레티노이드에 의한 활성억제를 나타내었다. 또한 부위특이적 변이와 ChIP분석은 -731에서 -722영역에 위치한 전사인자NF-kB 결합부위가 hST8Sia I의 레티노이드에 의한 활성억제에 중요하게 관여하고 있음을 나타내었다. 이러한 발현 억제는 PKC/ERK 신호전달경로를 통하여 일어난다는 것을 신호전달경로 저해제를 이용한 RT-PCR과 프로모터 활성조사에 의해 규명하였다.

• Asian-Australasian Journal of Animal Sciences
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• 제32권4호
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• pp.494-500
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• 2019

Objective: Feed consumption contributes a large percentage for total production costs in the poultry industry. Detecting genes associated with feeding traits will be of benefit to improve our understanding of the molecular determinants for feed efficiency. The objective of this study was to identify candidate genes associated with feed conversion ratio (FCR) via genomewide association study (GWAS) using sequence data imputed from single nucleotide polymorphism (SNP) panel in a Chinese indigenous chicken population. Methods: A total of 435 Chinese indigenous chickens were phenotyped for FCR and were genotyped using a 600K SNP genotyping array. Twenty-four birds were selected for sequencing, and the 600K SNP panel data were imputed to whole sequence data with the 24 birds as the reference. The GWAS were performed with GEMMA software. Results: After quality control, 8,626,020 SNPs were used for sequence based GWAS, in which ten significant genomic regions were detected to be associated with FCR. Ten candidate genes, ubiquitin specific peptidase 44, leukotriene A4 hydrolase, ETS transcription factor, R-spondin 2, inhibitor of apoptosis protein 3, sosondowah ankyrin repeat domain family member D, calmodulin regulated spectrin associated protein family member 2, zinc finger and BTB domain containing 41, potassium sodium-activated channel subfamily T member 2, and member of RAS oncogene family were annotated. Several of them were within or near the reported FCR quantitative trait loci, and others were newly reported. Conclusion: Results from this study provide valuable prior information on chicken genomic breeding programs, and potentially improve our understanding of the molecular mechanism for feeding traits.

• 대한화장품학회지
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• 제47권3호
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• pp.205-212
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• 2021

본 연구는 피부 섬유아세포에 자외선을 조사하거나 TNF-α를 처리하면 세포에 따라 MMP-1의 발현이 다르게 나타나는데, 이것이 MMP-1 프로모터의 다형성에 의해서 나타남을 밝히기 위해 수행되었다. 시판하는 23 종의 primary 섬유아세포에 대하여 MMP-1 프로모터의 -1607 부위의 유전형을 분석한 결과 6 개의 1G/1G 유전형, 10 개의 1G/2G 유전형, 7 개의 2G/2G 유전형을 가진 섬유아세포를 확인할 수 있었다. Hs68과 Detroit 551 세포주는 1G/2G 유전형을 가지는 것으로 확인되었다. 1G/1G 유전형은 TNF-α 처리에 의해 대조군에 비해 MMP-1이 2 배 높게 발현되었으며, 자외선에 의해서는 거의 발현되지 않았다. 1G/2G 유전형의 경우는 TNF-α 처리에 의해 MMP-1이 2.45 배 높게 발현되었으며, 자외선에 의해서는 1.4 배 MMP-1이 발현되었다. 2G/2G 유전형의 경우는 TNF-α 처리에 의해 MMP-1이 1.35 배 발현되었으며, 자외선에 의해서는 2.5 배로 높게 발현되었다. 즉 1G 유전형은 TNF-α에 의해, 2G 유전형은 자외선에 의해 발현이 유도되는 것으로 추정할 수 있으며, -1607 위치에 하나 더 삽입된 G에 의해서 Ets 전사인자가 결합할 수 있는 site가 만들어져서 MMP-1의 발현이 증가한다고 추정할 수 있으며, 피부 노화와 관련하여 섬유아세포에서는 이에 대한 연구가 전혀 진행되어 있지 않아서 향후 추가로 연구되어야 할 부분이다. 피부는 내인성 노화와 광노화의 영향을 동시에 받는 기관이므로, 피부 노화를 개선하기 위한 타겟으로 MMP-1의 발현을 분석할 경우에는 실험 조건에 적합한 유전형을 가지는 세포를 선택하여 연구를 진행하는 전략을 세워야 할 필요성이 대두된다.