• Fisheries and Aquatic Sciences
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• 제14권1호
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• pp.31-42
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• 2011

Three novel hepcidin isoforms were isolated and characterized from the perciform fish species Oplegnathus fasciatus. These hepcidin isoforms (designated rbhepc5, rbhepc6 and rbhepc7) were found to share a conserved, tripartite gene structure and a considerable sequence homology one another. A comparison of their mature peptide sequences with those of other perciform hepcidin orthologs indicated that these three hepcidin isoforms as well as four other isoforms previously identified in this species, appear to belong to the HAMP2 group of hepcidin genes. Analysis of the 5'-upstream sequences showed that the proximal non-coding regions of rbhepc5~7 do not possess canonical TATA signals; instead, they harbor several binding motifs for transcription factors involved in immune modulation. Reverse transcriptase-PCR analysis demonstrated that the rbhepc5~7 are expressed predominantly in the liver, and that the transcription of rbhepc5~7 is rapidly induced in the liver, but not in other tissues, by experimental challenge with any of three different bacterial species. However, transcription of rbhepc6 appeared to be negligible under both basal and stimulated conditions, as judged by the redundancy count of randomly chosen reverse transcriptase-PCR clones.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.499-505
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• 2012

Chemoprevention represents a strategy designed to protect cells or tissues against various carcinogens and carcinogenic metabolites derived from exogenous or endogenous sources. Recent studies indicate that plant-derived triterpenoids, like oleanolic acid, may exert cytoprotective functions via regulation of the activity of different transcription factors. The chemopreventive effects may be mediated through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor. Activation of Nrf2 by triterpenoids induces the expression of phase 2 detoxifying and antioxidant enzymes such as NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) - proteins which can protect cells or tissues against various toxic metabolites. On the other hand, inhibition of other transcription factors, like NF-${\kappa}B$ leads to the decrease in the pro-inflammatory gene expression. Moreover, the modulation of microRNAs activity may constitute a new mechanism responsible for valuable effects of triterpenoids. Recently, based on the structure of naturally occurring triterpenoids and with involvement of bioinformatics and computational chemistry, many synthetic analogs with improved biological properties have been obtained. Data from in vitro and in vivo experiments strongly suggest synthetic derivatives as promising candidates in the chemopreventive and chemotherapeutic strategies.

• Molecules and Cells
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• 제39권2호
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• pp.156-162
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• 2016

Estrogen receptor ${\alpha}$ (ER-${\alpha}$), which is involved in bone metabolism and breast cancer, has been shown to have transcriptional targets. Dlx3 is essential for the skeletal development and plays an important role in osteoblast differentiation. Various osteogenic stimulators and transcription factors can induce the protein expression of Dlx3. However, the regulatory function of ER-${\alpha}$ in the Dlx3 mediated osteogenic process remains unknown. Therefore, we investigated the regulation of Dlx3 and found that ER-${\alpha}$ is a positive regulator of Dlx3 transcription in BMP2-induced osteoblast differentiation. We also found that ER-${\alpha}$ interacts with Dlx3 and increases its transcriptional activity and DNA binding affinity. Furthermore, we demonstrated that the regulation of Dlx3 activity by ER-${\alpha}$ is independent of the ligand (estradiol) binding domain. These results indicate that Dlx3 is a novel target of ER-${\alpha}$, and that ER-${\alpha}$ regulates the osteoblast differentiation through modulation of Dlx3 expression and/or interaction with Dlx3.

• Journal of Digestive Cancer Research
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• 제6권1호
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• pp.6-10
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• 2018

The importance of signal transducer and activator of transcription 3 (STAT3) signaling in gastric carcinogenesis was firmly evaluated in the previous studies. Fully activated STAT3 induces various target genes involving tumor invasion and epithelial-mesenchymal transition (EMT), and mediates interaction between cancer cells and microenvironmental immune cells. Thus, suppression of STAT3 activity is an important issue for inhibition of gastric carcinogenesis and invasion. Unfortunately, data from clinical studies of direct inhibitor targeting STAT3 have been disappointing. SH2-containing protein tyrosine phosphatase 1 (SHP-1) effectively dephosphorylates and inhibits STAT3 activity, which has not been extensively studied gastric cancer research field. However, by summarizing recent data, it is evident that protein and gene expression of SHP-1 are minimal in gastric cancer cells, and induction of SHP-1 effectively downregulates phosphorylated STAT3 and inhibits cellular invasion in gastric cancer cells. Several SHP-1 inducers have been investigated in the experimental studies, including proton pump inhibitor, arsenic trioxide, and other natural compounds. Taken together, we suggest that modulation of SHP-1/STAT3 signaling axis may present a new way for treatment of gastric cancer, and development of effective SHP-1 inducer may be an important task in the future search field of gastric cancer.

• Natural Product Sciences
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• 제17권1호
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• pp.26-32
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• 2011

Novel tyrosinase inhibitors are important for pigmentation in the skin. Following extraction of tyrosinase inhibitors from edible vegetables or fruits, we found that the Prunus persica flesh extract (PPFE) exhibited potential inhibitory activity for melanogenesis. PPFE showed tyrosinase inhibitory activity in an enzymatic assay and PPFE also significantly inhibited the melanin formation in cultured mouse melan-a cells. Moreover, real-time RT-PCR analysis revealed that the inhibition of melanin production by PPFE was closely related to marked suppression of mRNA expression of tyrosinase and tyrosinase-related protein-1 and -2 (TRP-1 and TRP-2) in melan-a cells. Further investigation found that the modulation of tyrosinase expression by PPFE was associated with the transcriptional regulation of the microphthalmia-associated transcription factor (MITF). PPFE inhibited the promoter activity of MITF and suppressed MITF mRNA expression in melan-a cells. These results indicate that PPFE down-regulates melanogenesis-associated gene expression through MITF-mediated transcriptional regulation and these events might be related to the hypopigmentary effects of PPFE.

• BMB Reports
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• 제44권6호
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• pp.399-404
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• 2011

In this study, powder of Orostachys japonicus A. Berger (O. japonicus) was extracted with 95% ethyl alcohol and fractionated using a series of organic solvents, including n-hexane (hexane), dichloromethane (DCM), ethylacetate (EtOAc), n-butanol (BuOH), and water ($H_2O$). We investigated the anti-inflammatory effects of these O. japonicus extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Their effects on the expression of inflammatory mediators and transcription factors were analyzed by Western blotting. DCM fraction significantly inhibited formation of reactive oxygen species (ROS) as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Phosphorylation of the pro-inflammatory transcription factor complex nuclear factor-kappa B (NF-${\kappa}$B) p65 and expression of inducible nitric oxide synthase (iNOS), one of its downstream proteins, were also suppressed by DCM fraction. These effects were regulated by upsteam proteins in the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathways. Taken together, our data suggest that O. japonicus could be used as a potential source for anti-inflammatory agents.

• 한국동물학회지
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• 제28권2호
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• pp.108-119
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• 1985

Stress protein (SP) 遺傳子發現의 調節機構를 밝히기 위한 한가지 방편으로 환경의 stress와 pH가 SP의 合成誘導에 어떤 作用을 하는지를 SDS-PAGE를 이용해서 分析하였다. 蛋白質合成의 전반적 양상은 MEF와 SCK 세포에서 달랐으나 SP의 양상은 동일하였다. 그중에서 $SP_70$의 誘導와 感衰의 kinetics는 특히 흥미로웠다. $SP_70$의 kinetics는 酸性 pH와 正常 pH에서 類似하였으나 最大量의 SP 合成에 필요한 溫度와 그 處理時間은 pH에 의해 달리 나타나서, 酸性 pH 에서는 자은 溫度와 짧은 處理時間에서 나타나고 더욱 오래 지속되는 경향을 보였다. SP의 合成誘導와 SP mRNA의 축적은 actinomycin D에 의해 阻止되는 사실로 미루어 SP의 合成이 誘導되기 위해서는 새로운 mRNA의 合成이 필요함을 알수 있었고, cycloheximide 처리의 결과는 SP의 合成誘導에 앞서서 어떤 特異한 蛋白質의 合成은 일어나지는 않음을 알수 있었다. 이상과 같은 몇가지 實驗結果는 MEF와 SCK 세포에서 SP의 合成誘導는 일차적으로 轉寫水潗에서 調節되며, $SP_70$의 合成은 自動調節됨과 아울러 SP의 水潗은 세포늬 stress 상태와 相關關係가 있는 것으로 推論할수 있음을 보여주었다.

• 한국해양생명과학회지
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• 제7권2호
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• pp.145-153
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• 2022

수은은 생물 축적과 먹이사슬을 통한 생물 농축되며, 미량에서도 유해한 영향을 나타내기 때문에 해양 환경 내에서 중요한 문제가 되고 있다. 그러나 해양 소형 갑각류에 대한 수은의 생물 영향은 다른 금속에 비해 연구가 미흡하다. 본 연구에서는 기수산 물벼룩 Diaphanosoma celebensis을 아치사 농도(0.2, 0.4, 0.8 ㎍/l)의 무기 수은(HgCl₂)에 48시간 노출시킨 후, 대사 관련 유전자의 발현 양상을 조사하였다. 해독효소 유전자 5종(cytochrome P450; cyp360A1, cyp361A1, cyp4AP3, cyp4C122, cyp370C5)과 소화효소 6종(alpha amylase (AMY), alpha amylase related protein (AMY-like), trypsin (TRYP), chymotrypsin-like protein (CHY), lipase (LIP), pancreatic lipase-related protein (PLRP))의 유전자 발현을 quantitative real time reverse transcription polymerase chain reaction (qRT-PCR)을 이용하여 분석하였다. Cyp 유전자의 경우 clan2에 속하는 cyp370C5와 clan4에 속하는 cyp4AP3 유전자의 발현이 농도 의존적으로 유의하게 증가하였다. 한편 소화효소 유전자 중에서는 단백질 소화와 관련 있는 TRYP 유전자의 발현이 농도 의존적으로 증가하였다. 이러한 결과는 cyp370C5와 cyp4AP3가 수은 독성을 해독하는 과정에서 중요한 역할을 담당할 것으로 보이며, 수은이 소화효소 유전자의 발현을 조절함으로써 에너지 대사에 영향을 미칠 수 있음을 제시한다. 본 연구는 해양 소형 갑각류에서 수은에 대한 분자 수준의 영향을 이해하는데 도움이 될 것이다.

• Asian-Australasian Journal of Animal Sciences
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• 제29권8호
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• pp.1102-1110
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• 2016

The mammalian target of rapamycin (mTOR) regulates cellular processes such as cell growth, metabolism, transcription, translation, and autophagy. Rapamycin is a selective inhibitor of mTOR, and induces autophagy in various systems. Autophagy contributes to clearance and recycling of macromolecules and organelles in response to stress. We previously reported that vitrified-warmed mouse oocytes show acute increases in autophagy during warming, and suggested that it is a natural response to cold stress. In this follow-up study, we examined whether the modulation of autophagy influences survival, fertilization, and developmental rates of vitrified-warmed mouse oocytes. We used rapamycin to enhance autophagy in metaphase II (MII) oocytes before and after vitrification. The oocytes were then subjected to in vitro fertilization (IVF). The fertilization and developmental rates of vitrified-warmed oocytes after rapamycin treatment were significantly lower than those for control groups. Modulation of autophagy with rapamycin treatment shows that rapamycin-induced autophagy exerts a negative influence on fertilization and development of vitrified-warmed oocytes.

• Molecules and Cells
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• 제42권2호
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• pp.123-134
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• 2019

Lysophosphatidic acid (LPA) is an endogenous lysophospholipid with signaling properties outside of the cell and it signals through specific G protein-coupled receptors, known as $LPA_{1-6}$. For one of its receptors, $LPA_1$ (gene name Lpar1), details on the cis-acting elements for transcriptional control have not been defined. Using 5'RACE analysis, we report the identification of an alternative transcription start site of mouse Lpar1 and characterize approximately 3,500 bp of non-coding flanking sequence 5' of mouse Lpar1 gene for promoter activity. Transient transfection of cells derived from mouse neocortical neuroblasts with constructs from the 5' regions of mouse Lpar1 gene revealed the region between -248 to +225 serving as the basal promoter for Lpar1. This region also lacks a TATA box. For the region between -761 to -248, a negative regulatory element affected the basal expression of Lpar1. This region has three E-box sequences and mutagenesis of these E-boxes, followed by transient expression, demonstrated that two of the E-boxes act as negative modulators of Lpar1. One of these E-box sequences bound the HeLa E-box binding protein (HEB), and modulation of HEB levels in the transfected cells regulated the transcription of the reporter gene. Based on our data, we propose that HEB may be required for a proper regulation of Lpar1 expression in the embryonic neocortical neuroblast cells and to affect its function in both normal brain development and disease settings.