• Journal of Ginseng Research
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• 제40권2호
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• pp.135-140
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• 2016

Background: Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng. Methods: The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. Results: The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. Conclusion: FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNKep53ecaspase-3 signaling cascade.

• Journal of Ginseng Research
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• 제42권1호
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• pp.81-89
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• 2018

Background: BIOGF1K, a compound-K-rich fraction, has been shown to display anti-inflammatory activity. Although Panax ginseng is widely used for the prevention of photoaging events induced by UVB irradiation, the effect of BIOGF1K on photoaging has not yet been examined. In this study, we investigated the effects of BIOGF1K on UVB-induced photoaging events. Methods: We analyzed the ability of BIOGF1K to prevent UVB-induced apoptosis, enhance matrix metalloproteinase (MMP) expression, upregulate anti-inflammatory activity, reduce sirtuin 1 expression, and melanin production using reverse transcription-polymerase chain reaction, melanin content assay, tyrosinase assay, and flow cytometry. We also evaluated the effects of BIOGF1K on the activator protein-1 signaling pathway, which plays an important role in photoaging, by immunoblot analysis and luciferase reporter gene assays. Results: Treatment of UVB-irradiated NIH3T3 fibroblasts with BIOGF1K prevented UVB-induced cell death, inhibited apoptosis, suppressed morphological changes, reduced melanin secretion, restored the levels of type I procollagen and sirtuin 1, and prevented mRNA upregulation of MMP-1, MMP-2, and cyclo-oxygenase-2; these effects all occurred in a dose-dependent manner. In addition, BIOGF1K markedly reduced activator-protein-1-mediated luciferase activity and decreased the activity of mitogen-activated protein kinases (extracellular response kinase, p38, and C-Jun N-terminal kinase). Conclusion: Our results strongly suggest that BIOGF1K has anti-photoaging activity and that BIOGF1K could be used in anti-aging cosmeceutical preparations.

• Journal of Plant Biotechnology
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• 제36권3호
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• pp.281-288
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• 2009

Seed germination is the important stage to express many genes for regulation of energy metabolism, starch degradation and cell division from seed dormancy state. For the functional analysis of seed germination mechanisms, we were analyzed the rice cDNA clones (Oryzasativa cultivar Ilpum) obtained from seed imbibition during 48 hours. Total number of 18,101 Expressed Sequence Tags (ESTs) were clustered using SeqMan program. Among them, 8,836 clones were identified as unique clones. We identified the chitinase gene specifically expressed in seed germination and amylase gene involved to starch degradation from the full length cDNA analysis, and several genes were registered to NCBI GeneBank. To analyzed the commonly expressed genes between inmature seed and germinated seed, 25,66 inmature ESTs and 18,101 germinated ESTs were clustered using SeqMan program and identified 2,514 clones as commonly expressed unigene. Among them, alpha-glubulin and alcohol dehydrogenase I were supposed to LEA genes only expressed in the immature and germinated seed stages. For the clustering of orthologous group genes, we further analyzed the 8,836 EST clones from germinating seeds using NCBI clusters of orthologous groups database. Among the clones, 5,076 clones were categorized into information storage and processing, cellular processes and signaling, metabolism and poorly characterized genes, proportioning 783 (14.29%), 1,484 (27%), 1,363 (24.8%) and 1,869 (34%) clones to the previous four categories, respectively.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4469-4475
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• 2015

Transient receptor potential melastain 7 (TRPM7) is a bifunctional protein with dual structure of both ion channel and protein kinase, participating in a wide variety of diseases including cancer. Recent researches have reported the mechanism of TRPM7 in human cancers. However, the correlation between TRPM7 and prostate cancer (PCa) has not been well studied. The objective of this study was to investigate the potential the role of TRPM7 in the apoptosis of PC-3 cells, which is the key cell of advanced metastatic PCa. In this study, we demonstrated the influence and potential function of TRPM7 on the PC-3 cells apoptosis induced by TNF-related apoptosis inducing-ligand (TRAIL). The study also found a novel up-regulated expression of TRPM7 in PC-3 cells after treating with TRAIL. Suppression of TRPM7 by TRPM7 non-specific inhibitors ($Gd^{3+}$ or 2-aminoethoxy diphenylborate (2-APB) ) not only markedly eliminated TRPM7 expression level, but also increased the apoptosis of TRAIL-treated PC-3 cells, which may be regulated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway accompany with up-regulated expression of cleaved Caspase-3, (TRAIL-receptor 1, death receptors 4) DR4, and (TRAIL-receptor 2, death receptors 5) DR5. Taken together, our findings strongly suggested that TRPM7 was involved in the apoptosis of PC-3 cells induced by TRAIL, indicating that TRPM7 may be applied as a therapeutic target for PCa.

• BMB Reports
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• 제46권8호
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• pp.422-427
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• 2013

Although BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be fully elucidated. Here, we explore the possible involvement and detail role of JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9-induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by SP600125 treatment in MSCs. The effects of inhibitor are reproduced with adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What is most noteworthy, however, is that inhibition of JNKs activity resulted in reduction of BMP9-induced osteogenic differentiation of MSCs, implying that activation of JNKs is essential for BMP9 osteoinductive activity.

• 한국발생생물학회지:발생과생식
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• 제15권1호
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• pp.61-69
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• 2011

Previously, we have shown that Bcl2l10 as a member of Bcl-2 family, key regulators of the apoptotic process, is dominantly expressed in oocytes of ovary but several member of the Bcl-2 family are not expressed in oocytes. Recent our studies had been processed about roles and regulatory mechanisms of Bcl2l10 in oocytes. Microinjection of Bcl2l10 RNAi into the cytoplasm of germinal vesicle oocytes resulted in metaphase I (MI) arrest and exhibited abnormalities in their spindles and chromosome configurations (Yoon et al., 2009). The present study was conducted to elucidate the downstream genes regulated by Bcl2l10 and signaling networks in Bcl2l10 RNAi microinjected oocytes by using microarray analysis. Surprisingly, we found that a large proportion of genes regulated by Bcl2l10 RNAi were involved in the cell cycle and actin skeletal system regulation as important upstream genes of Bcl2l10. Among the transcripts with highly significant fold changes more than 2-fold, Tpx2 and Cep192 are 16.1- and 8.2-fold down regulated respectively by Bcl2l10 RNAi. Tpx2 and Cep192 are known as cofactors that control Aurora A kinase activity and localization. Therefore, we concluded that Bcl2l10 may have important roles during oocyte meiosis as functional upstream regulator of Tpx2 and Cep192.

• Molecules and Cells
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• 제39권2호
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• pp.103-110
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• 2016

As a degenerative joint disease, osteoarthritis (OA) constitutes a major cause of disability that seriously affects the quality of life of a large population of people worldwide. However, effective treatment that can successfully reverse OA progression is lacking until now. The present study aimed to determine whether two small non-coding RNAs miR-29a and miR-140, which are significantly down-regulated in OA, can be applied together as potential therapeutic targets for OA treatment. MiRNA synergy score was used to screen the miRNA pairs that potentially synergistically regulate OA. An in vitro model of OA was established by treating murine chondrocytes with IL-$1{\beta}$. Transfection of miR-29a and miR-140 via plasmids was investigated on chondrocyte proliferation and expression of nine genes such as ADAMTS4, ADAMTS5, ACAN, COL2A1, COL10A1, MMP1, MMP3, MMP13 and TIMP metallopeptidase inhibitor 1 (TIMP1). Western blotting was used to determine the protein expression level of MMP13 and TIMP1, and ELISA was used to detect the content of type II collagen. Combined use of miR-29a and miR-140 successfully reversed the destructive effect of IL-$1{\beta}$ on chondrocyte proliferation, and notably affected the MMP13 and TIMP1 gene expression that regulates extracellular matrix. Although co-transfection of miR-29a and miR-140 did not show a synergistic effect on MMP13 protein expression and type II collagen release, but both of them can significantly suppress the protein abundance of MMP13 and restore the type II collagen release in IL-$1{\beta}$ treated chondrocytes. Compared with single miRNA transfection, cotransfection of both miRNAs exceedingly abrogated the suppressed the protein production of TIMP1 caused by IL-$1{\beta}$, thereby suggesting potent synergistic action. These results provided1novel insights into the important function of miRNAs' collaboration in OA pathological development. The reduced MMP13, and enhanced TIMP1 protein production and type II collagen release also implies that miR-29a and miR-140 combination treatment may be a possible treatment for OA.

• 생명과학회지
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• 제15권3호
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• pp.344-351
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• 2005

산화질소(NO)와 칼슘 결합 단백질은 중추신경계의 다양한 세포들에서 나타나며, 이들은 각각 중요 신호전달 분자와 칼슘 완충 분자이다. 본 연구는 햄스터의 시각피질에서 뇌산화질소 합성효소 (nNOS)와 parvalbumin을 포함하는 뉴런들의 분포와 이들의 co-localization 양상을 면역세포화학적 기법을 이용하여 알아보았다. 햄스터 시각피질에서 parvalbumin에 대한 면역 반응성을 나타내는 뉴런들의 전체 수는 nNOS에 대한 면역 반응성을 보이는 뉴런들의 수보다 17배나 많았다. 가장 큰 차이는 시각피질 제5충에서 발견되었으며, 이곳에서 parvalbumin-면역 반응성 뉴런이 nNOS-면역 반응성 뉴런들의 수보다 54.7배나 높았다. nNOS-또는 parvalbumin-면역 반응성 뉴런들은 크기와 형태, 분포 방식이 시각피질에서 유사하게 나타났다. 그러나 이색 면역형광 기법은 햄스터 시각피질에서 nNOS와 parvalbumin을 모두 발현하는 뉴런은 없음을 보여주었다. 본 연구의 결과는 nNOS와 칼슘 결합 단백질 사이의 co-localization양상이 종간에 차이가 존재함을 나타내며 또한 시각피질에 있는 nNOS-면역 반응성 뉴런들의 다양성과 이질성뿐만 아니라 동물 다양성 이해의 중요성을 함께 제시한다고 볼 수 있다.

• 대한임상검사과학회지
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• 제50권2호
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• pp.177-182
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• 2018

본 연구는 zerumbone이 단구의 유주에 어떠한 영향을 미치는지 알아보고자 진행되었다. 단구는 다양한 염증 질환의 중요한 매개자로 인식되고 있으며, 활성, 유주 등 단구의 기능 조절을 통해 염증 질환을 조절하는 가능성이 보고 되고 있다. 염증 발생 시 증가하는 케모카인인 MCP-1에 의해 단핵구 세포주 THP-1의 유주가 유발되는 것을 확인하였다. 10 ng/mL의 농도에서 유주가 발생하였으며, 100 ng/mL과 200 ng/mL의 농도에서 가장 높은 유주 현상이 나타났다. MCP-1에 의해 유발된 THP-1 유주는 zerumbone 존재 시 50% 이상 감소하였다. MCP-1 수용체인 CCR2 신호전달 과정의 중요 2차 전달자인 cAMP의 배양액 내 농도는 zerumbone 단독 처리 시 세포 단독 배양 조건에 비해 증가하였으며, MCP-1 단독 처리 시에는 의미있게 감소하였다. 그러나, zerumbone과 MCP-1을 동시에 처리했을 때에는 다시 cAMP의 증가가 관찰되었다. MCP-1 처리에 의해 일어나는 Erk 인산화도 zerumbone과 동시 처리 시 감소하는 결과를 확인했다. 본 연구는 염증성 질환에 중요한 매개자로 인식되고 있는 단구의 유주 현상을 조절하는 zerumbone의 가능성을 보여준다.

• 생명과학회지
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• 제21권11호
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• pp.1641-1651
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• 2011

TNF ligand 군에 속하는 Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L)은 death receptor를 통한 세포사멸을 유도하는 것으로 알려졌다. TRAIL은 정상세포에서는 세포사를 일으키지 않고 암세포에서만 특이적으로 세포사멸을 유도함으로써 잠재력 있는 항암제로 주목을 받고 있다. 그러나, 최근 연구에 의하면 악성 신장암과 간암과 같은 일부 암에서는 TRAIL에 의한 세포사에 저항성을 가지는 것으로 알려져 있다. 그러므로, TRAIL 만으로는 다양한 악성종양을 위한 치료법으로 적절하지 않다. TRAIL에 대한 저항성을 가지는 분자적 기전을 이해하고, TRAIL 저항성을 극복할 수 있는 증감제를 밝혀내는 것이 보다 효율적인 TRAIL을 이용한 암세포 치료 전략에 필요하다. 화학치료제들이 TRAIL 수용체인 death receptor의 발현을 증가시키고, 세포 내의 TRAIL에 의한 신호전달 체계를 활성화 시키는 것으로 알려져 있고, 이러한 기전을 통하여 다양한 화학치료제들이 TRAIL에 의한 세포사멸을 증가시키는 것을 확인하였다. 이 논문에서, 우리는 TRAIL에 의한 세포 사멸을 증가시키기 위한 생물학적 약물을 정리하고, 그 분자적 기전을 고찰한다.