• Environmental Analysis Health and Toxicology
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• 제18권4호
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• pp.249-254
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• 2003

본 연구는 환경호르몬(endocrine disruptors)으로 분류되었으며, 에스트로젠 화합물의 특성을 지닌 4-Nonylphenol (NP)이 설치류 Pituitary 세포 중 성장호르몬을 분비하는 GH3 세포의 Nitric oxide(NO)을 증가시키는 작용기전을 규명코자 수행되었다 먼저 GH3세포에 NP처리 농도에 따른 NO의 생성을 측정한 결과 NP처리농도 의존적으로 증가시켰다. 이러한 NO의 증가가 genomic action인지를 확인하기 위해 GH3세포의 NO를 증가시키는 효소인 neuronal oxide synthase의 단백질량을 측정한 결과 GH3세포에서 NP에 의한 nNOS의 단백질의 변화는 없었다. 에스트로젠 화합물인 NP가 에스트로젠 리셉터 (ER)와의 관계를 조사하기 위해 ER억제제(ICI 168,780)클 처리한 경우 NP에 의해 증가한 NO가 감소하였다. 또한 유전자 전사억제제인 actinomycin D 및 단백질 발현 억제제인 cycloheximide을 처리한 경우는 NP에 의한 NO 증가억제효과가 없었다. 이러한 결과를 종합해 볼 때 GH3 세포에서 NP는 ER을 매개한 non-genomic action에 의해 NO를 증가키는 것으로 사료된다.

• 한국발생생물학회지:발생과생식
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• 제10권2호
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• pp.85-92
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• 2006

본 논문은 포유동물 난소에서의 신속한 프로게스테론(P4) 선호 전달경로에 관해 현재 통용되는 지식을 요약하였다. P4는 안드로겐과 에스트로겐 합성 과정에서의 중요한 중간 산물이면서 그 자체로도 배란, 난포폐쇄(atresia), 황체형성과정(luteinization)에서 결정적인 역할을 하며, 모든 포유동물의 초기 임신 유지에 필수적이다. 이와 같은 생리적인 중요성에도 불구하고 포유동물 난소에서의 정확한 P4 작용기작은 아직까지도 완전히 알려져 있지 않다. 이러한 관점에서 볼 때, 비유전자 수준이면서 전사와 무관한 P4의 세포내 작용을 매개하는 수용체의 실체에 관해 오래 동안 계속된 의문과 논란은 과학적인 흥미를 유발하는 생식생리학의 주요 관심사이다. 포유류 난소에서 P4는 1) 잘 알려진 유전자 수준의 경로(genomic pathway)인 호르몬이 소위 고전적인 세포 내의 수용체에 결합하고, 이어 리간드-호르몬 복합체가 전사조절물질로 작용하여 표적 유전자 발현을 조절하거나, 2) 유전자에 직접 작용하지 않기 때문에 비유전자 수준이라 불리우는 경로(non-genomic pathway)로 작용한다. P4의 비유전자 수준 작용의 주요한 특징은 (i) 신속하고, (ii) 전사억제제에 반응하지 않고, (iii) 세포막과 연관된 물질들에 의해 신호가 전달된다. 아마도 난소에서 P4의 비유전자 수준 작용은 (a) 세포막 또는 그 근처에 위치한 고전적인 P4 수용체(PGR), (b) 세포막 프로게스틴 수용체(membrane progestin receptors; MPR $\alpha$, MPR $\beta$ and MPR $\gamma$) 패밀리, (c) progesterone receptor membrane component I(PGRMC1), 그리고 (d) serpine I mRNA binding protein(SERBP1)의 세포막 복합체에 의해 매개되는 것으로 추정된다. 포유류 난소에서의 P4 작용에 대한 완전한 이해를 위해서는 향후 많은 연구가 필요할 것이다.

• 대한약학회:학술대회논문집
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• 대한약학회 2004년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.105-105
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• 2004

• The Korean Journal of Physiology and Pharmacology
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• 제7권4호
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• pp.217-221
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• 2003

To clarify the roles of gonadal steroids on pancreatic exocrine secretion, effects of progesterone and estradiol-$17{\beta}$ on spontaneous and secretagogue-induced exocrine response of isolated perfused rat pancreas were investigated. Intra-arterial infusion of progesterone resulted in significant increase of the spontaneous pancreatic fluid and amylase secretion dose-dependently. However, estradiol-$17{\beta}$ did not exert any influence on spontaneous pancreatic exocrine secretion. Exogenous secretin, cholecystokinin (CCK), and acetylcholine markedly stimulated pancreatic fluid and amylase secretion. Progesterone initially enhanced secretin-induced amylase secretion, but this stimulatory response declined thereafter to basal value. Moreover, secretin-induced fluid secretion was not affected by infusion of progesterone. Therefore, initial increase of secretion-induced amylase secretion by progesterone seems to be a non-specific action by washout effect of secretin. Estradiol-$17{\beta}$ failed to change the secretin-induced fluid and amylase secretion. Both progesterone and estradiol-$17{\beta}$ did not exert any influence on CCK-induced fluid and amylase secretion. Acetylcholine-induced exocrine secretion of isolated perfused pancreas also was not affected by intra-arterial infusion of progesterone or estradiol-$17{\beta}$. It is concluded from the above results that progesterone could enhance the spontaneous pancreatic fluid and amylase secretion of isolated perfused rat pancreas through non-genomic shortterm action, and that these effects could be masked by more potent stimulants such as secretin, CCK, and acetylcholine.

• 약학회지
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• 제54권3호
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• pp.180-186
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• 2010

Aldosterone, mineralocorticoid hormone, has important functions related to the regulation of blood pressure and balance of fluids and electrolytes in the distal region of the nephron. By genomic and non-genomic action of aldosterone, the physiological kidney functions are modulated. However, many of them except several kind of sodium channel have not been identified and analyzed yet. In this study, proteomic technologies with two-dimensional gel electrophoresis (2-DE) gel using aldosterone rat model were applied to analyze and identify the aldosterone dependently expressed proteins in rat kidney cortex. As a result, the established aldosterone rat model exhibited the normal physiological responses to aldosterone and modulated proteins were identified, which included 15 increased and 3 decreased proteins on 2-DE analysis. Among them, 11 proteins were identified as changed proteins by LC-MS/MS analysis. These proteins identified as aldosterone induced proteins were involved in several cellular pathways such as cytoskeleton remodeling, energy metabolism, amino acid metabolism, and chaperone process. In conclusion, our data could provide the insights into the new mechanism underlying regulation of kidney functions by aldosterone.

• Genomics & Informatics
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• 제19권4호
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• pp.43.1-43.12
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• 2021

Campylobacter jejuni is one of the most prevalent organisms associated with foodborne illness across the globe causing campylobacteriosis and gastritis. Many proteins of C. jejuni are still unidentified. The purpose of this study was to determine the structure and function of a non-annotated hypothetical protein (HP) from C. jejuni. A number of properties like physiochemical characteristics, 3D structure, and functional annotation of the HP (accession No. CAG2129885.1) were predicted using various bioinformatics tools followed by further validation and quality assessment. Moreover, the protein-protein interactions and active site were obtained from the STRING and CASTp server, respectively. The hypothesized protein possesses various characteristics including an acidic pH, thermal stability, water solubility, and cytoplasmic distribution. While alpha-helix and random coil structures are the most prominent structural components of this protein, most of it is formed of helices and coils. Along with expected quality, the 3D model has been found to be novel. This study has identified the potential role of the HP in 2-methylcitric acid cycle and propionate catabolism. Furthermore, protein-protein interactions revealed several significant functional partners. The in-silico characterization of this protein will assist to understand its molecular mechanism of action better. The methodology of this study would also serve as the basis for additional research into proteomic and genomic data for functional potential identification.

• Biomolecules & Therapeutics
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• 제29권2호
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• pp.234-247
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• 2021

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the Erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2006년도 Principles and Practice of Microarray for Biomedical Researchers
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• pp.83-89
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• 2006

Cellular functions are carried out by a concerted action of biochemical pathways whose components have genetic interactions. Abnormalities in the activity of the genes that constitute or modulate these pathways frequently have oncogenic implications. Therefore, identifying the upstream regulatory genes for major biochemical pathways and defining their roles in carcinogenesis can have important consequences in establishing an effective target-oriented antitumor strategy We have analyzed the gene expression profiles of human liver cancer samples using cDNA microarray chips enriched in liver and/or stomach-expressed cDNA elements, and identified groups of genes that can tell tumors from non-tumors or normal liver, or classify tumors according to clinical parameters such as tumor grade, age, and inflammation grade. We also set up a high-throughput cell-based assay system (cell chip) that can monitor the activity of major biochemical pathways through a reporter assay. Then, we applied the cell chip platform for the analysis of the HCC-associated genes discovered from transcriptome profiling, and found a number of cancer marker genes having a potential of modulating the activity of cancer-related biochemical pathways such as E2F, TCF, p53, Stat, Smad, AP-1, c-Myc, HIF and NF-kB. Some of these marker genes were previously blown to modulate these pathways, while most of the others not. Upon a fast-track phenotype analysis, a subset of the genes showed increased colony forming abilities in soft agar and altered cell morphology or adherence characteristics in the presence of purified matrix proteins. We are currently analyzing these selected marker genes in more detail for their effects on various biological Processes and for Possible clinical roles in liver cancer development.