• 생명과학회지
• /
• 제30권6호
• /
• pp.501-512
• /
• 2020

제주조릿대 잎은 항염, 해열 및 이뇨작용을 가지고 있어 위궤양, 목마름 및 토혈 치료를 위한 민간의약으로 사용되어 왔다. 본 저자들은 제주조리대 잎에서 분리한 피토케미칼 풍부 추출물(PRE)과 그 에틸아세테이트 분획물(EPRE)은 여러 위암 세포주에서 세포사멸을 유도하는 항암 효과가 있다고 보고한 바 있다. 본 연구는 EPRE의 세포사멸 유도 기전에 관여하는 분자표적들을 탐색하기 위하여 EPRE을 처리한 SNU-16 세포에서 mRNA와 microRNA (miRNA)의 프로파일 변화를 분석하였다. RNA sequencing 분석을 통해 총 2,875개의 차등적으로 발현되는 유전자들(DEGs)을 동정하였다. 유전자 온톨로지(GO)와 KEGG 경로 분석 결과, EPRE는 세포사멸, 유사 분열-활성화 단백질 키나제(MAPK) 및 염증 반응, 종양 괴사 인자(TNF) 신호 전달 및 암 경로에 관여하는 유전자들의 발현을 조절하는 것으로 나타났다. 단백질-단백질 상호 작용(PPI) 네트워크 분석으로 세포사멸 및 세포죽음과 관련된 유전자들 간의 상호작용들을 확인할 수 있었다. 그리고, miRNA sequencing 분석을 통해 총 27개의 차별적으로 발현되는 miRNAs (DEMs)를 동정하였다. GO와 KEGG 경로 분석 결과, EPRE는 세포주기, 세포사멸 및 tropomyosin-receptor-kinase (TRK) 수용체 신호 전달, 성장인자-β(TGF-β), 핵인자 κB (NF-κB) 및 암 경로에 관여하는 miRNAs의 발현을 조정하였다. 본 연구결과는 EPRE의 항암 효과의 근본적인 메커니즘에 대한 통찰력을 제공한다.

• 한방안이비인후피부과학회지
• /
• 제21권3호
• /
• pp.52-68
• /
• 2008

Objectives and Methods : Salviae miltiorrhizae Radix (SMR) promotes blood circulation to remove blood stasis, cools the blood to relieve carbuncle, clears away heat from the heart and tranquilizes the mind. This study was designed to investigate the effects of SMR on immuno-potentiative action in terms of changes in the genetic profile of dendritic cells (DC) using by microarray analysis. Results and Conclusion: In this experiment, treatments with more than 250 ${\mu}g/ml$ upto 1000 ${\mu}g/ml$ of SMR elevated the proliferation rates of DC. Microscopic observations confirmed the tendency on proliferation rates. Expression levels of genes related with cellular methabolic process, cell communication, and macromolecule metabolic process were elevated by treatment with SMR in comparison of functional distribution in a Biological Process. In molecular functions, expression levels of genes related with receptor activation, nucleotide binding and nucleic acid binding were elevated. In cellular components, expression levels of genes related to cellular membrane-bound organelles were elevated. In addition, expression levels of genes related to Wnt signalling pathways and the glycerophospholipid metabolism were elevated through analysis using pathway analysis between up-and down-regulated genes in cells treated with SMR. Finally, genes related to JAK2, GRB2, CDC42, SMAD4, B2M, FOS and ESRI located the center of Protein interaction network of genes through treatment with SMR.

• Asian-Australasian Journal of Animal Sciences
• /
• 제14권3호
• /
• pp.358-364
• /
• 2001

The physiochemical properties and interactions between porcine blood and waxy rice were determined. Addition of calcium chloride (0.15%) improved acceptability of blood cake and increased the gelatinization degree of waxy rice. The water-holding capacity of porcine blood gel (blood/water=60/40, v/v), extent of absorption and gelatinization of waxy rice, and scanning electron microscopy showed that blood protein matrix and waxy rice are competitors for holding water in the cooking procedure. Non-haem iron content increased linearly (R=0.95) when heating temperature rose. The presence of blood proteins caused increasing of peak temperature (Tp) of gelatinization in differential scanning calorimetric thermal gram, The microstnlcture of plasma proteins and haemoglobin appeared continuous changes, and interacted with surface of waxy rice flour in terms of network and mosaic form, respectively. The electrophoretic patterns revealed an interaction between plasma proteins and waxy rice glutelin and haemoglobin when heated could be found at temperatures above $60^{\circ}C$.

• IMMUNE NETWORK
• /
• 제1권1호
• /
• pp.14-25
• /
• 2001

Background: Bone marrow stromal cells (BMSCs) express many cell surface molecules, which regulate the proliferation and differentiation of immune cells within the bone marrow. Methods: To identify cell surface molecules, which can regulate cell proliferation through cell interaction, monoclonal antibodies (MoAbs) against BMSCs were produced. Among them, 1H8 MoAb, which recognized distinctly an 80 kDa protein, abolished myeloma cell proliferation that was induced by co-culturing with BMSCs. Results: IL-6 gene expression was increased when myeloma or stromal cells were treated with 1H8 MoAb. In addition, the expression of IL-6 receptor and CD40 was up-regulated by 1H8 treatment, suggesting that the molecule recognized by 1H8 MoAb is involved in cell proliferation by modulating the expression of cell growth-related genes. Myeloma cells contain high levels of reactive oxygen species (ROS), which are related to gene expression and tumorigenesis. Treatment with 1H8 decreased the intracellular ROS level and increased PAG antioxidant gene concomitantly. Finally, 1H8 induced the tyrosine phosphorylation of several proteins in U266. Conclusion: Taken together, 1H8 MoAb recognized the cell surface molecule and triggered the intracellular signals, which led to modulate gene expression and cell proliferation.

• Journal of Ginseng Research
• /
• 제41권4호
• /
• pp.566-571
• /
• 2017

Background: A number of reports have described the protective effects of ginsenoside Rg1 (Rg1) in Alzheimer's disease (AD). However, the protective mechanisms of Rg1 in AD remain elusive. Methods: To investigate the potential mechanisms of Rg1 in ${\beta}$-amyloid peptide-treated SH-SY5Y cells, a comparative proteomic analysis was performed using stable isotope labeling with amino acids in cell culture combined with nano-LC-MS/MS. Results: We identified a total of 1,149 proteins in three independent experiments. Forty-nine proteins were significantly altered by Rg1 after exposure of the cells to ${\beta}$-amyloid peptides. The protein interaction network analysis showed that these altered proteins were clustered in ribosomal proteins, mitochondria, the actin cytoskeleton, and splicing proteins. Among these proteins, mitochondrial proteins containing HSD17B10, AARS2, TOMM40, VDAC1, COX5A, and NDUFA4 were associated with mitochondrial dysfunction in the pathogenesis of AD. Conclusion: Our results suggest that mitochondrial proteins may be related to the protective mechanisms of Rg1 in AD.

• Asian-Australasian Journal of Animal Sciences
• /
• 제25권10호
• /
• pp.1481-1492
• /
• 2012

The interaction of the genes involved in intestinal development is the molecular basis of the regulatory mechanisms of intestinal development. The objective of this study was to identify the significant pathways and key genes that regulate intestinal development in Landrace piglets, and elucidate their rules of operation. The differential expression of genes related to intestinal development during suckling time was investigated using a porcine genome array. Time sequence profiles were analyzed for the differentially expressed genes to obtain significant expression profiles. Subsequently, the most significant profiles were assayed using Gene Ontology categories, pathway analysis, network analysis, and analysis of gene co-expression to unveil the main biological processes, the significant pathways, and the effective genes, respectively. In addition, quantitative real-time PCR was carried out to verify the reliability of the results of the analysis of the array. The results showed that more than 8000 differential expression transcripts were identified using microarray technology. Among the 30 significant obtained model profiles, profiles 66 and 13 were the most significant. Analysis of profiles 66 and 13 indicated that they were mainly involved in immunity, metabolism, and cell division or proliferation. Among the most effective genes in these two profiles, CN161469, which is similar to methylcrotonoyl-Coenzyme A carboxylase 2 (beta), and U89949.1, which encodes a folate binding protein, had a crucial influence on the co-expression network.

• IMMUNE NETWORK
• /
• 제6권2호
• /
• pp.59-66
• /
• 2006

Background: CM1 (Centrocyte/-blast Marker I) defined by a mAb developed against concanavalin-A activated PBMC, is expressed specifically on a subpopulation of centroblasts and centrocytes of human germinal center (GC) B cells. Burkitt lymphoma (BL) is a tumor consisting of tumor cells with the characteristics of GC B cell. Previously we reported that CM1 ligation with anti-CM1 mAb induced apoptosis in Ramos $(IgM^{high})$ and Raji $(IgM^{low})$ cells. Methods & Results: In the present study, we observed that CM1 ligation with anti-CM1 mAb induced Fas ligand and Fas expression in Ramos cells, but not in Raji cells. Furthermore, anti-Fas blocking antibody, ZB4, blocked CM1-mediated apoptosis effectively in Ramos cells, but not in Raji cells. Increased mitochondrial membrane permeabilization, which was measured by $DiOC_6$, was observed only in Raji cells. In contrast to no significant change of Bax known as pro-apoptotic protein, anti-apoptotic protein Bcl-2 was significantly decreased in Raji cells. In addition, we observed that CM1 ligation increased release of mitochondrial cytochrome c and upregulated caspase-9 activity in Raji cells. Conclusion: These results suggest that apoptosis induced by CM1-ligation is mediated by Fas-Fas ligand interaction in Ramos cells, whereas apoptosis is mediated by down-regulation of Bcl-2 and subsequent decrease of mitochondrial membrane potential in Raji cells.

• IMMUNE NETWORK
• /
• 제2권2호
• /
• pp.72-78
• /
• 2002

Background: The precise mechanism by which CTLA-4 regulates T cell immune responses is still not fully understood. Previously we proposed that CTLA-4 could downregulate T cell function by modulating a signaling cascade initiated from the T cell receptor complex. The evidence for this notion comes from our findings that CTLA-4 associated with the T cell receptor zeta (TCR zeta) chain, and hence regulated TCR zeta phosphorylation by co-associated SHP-2 tyrosine phosphatase (1). In this report, we investigated whether any other signaling molecules could be involved in the CTLA-4 signaling pathway. Methods: We have taken biochemical approaches, such as immunoprecipitation followed by autoradiography or immunoblotting, to identify the molecules associated with CTLA-4. To perform these assays, we used activated primary T cells and ectopically transfected 293 cells. Various truncation mutants of CTLA-4 were used to map the interaction site on CTLA-4. Results: We found that in addition to TCR zeta and SHP-2, a recently cloned small adaptor molecule, SAP (SLAM-associated protein), was also able to associate with CTLA-4. We identified the domain of SAP association in CTLA-4 being a motif involving GVYVKM. This motif has been previously found to bind SHP-2 through its phosphorylated tyrosine interaction with SH-2 domain of SHP-2. Indeed, co-expression of SAP and SHP-2 reduced their binding to CTLA-4 significantly, suggesting that SAP and SHP-2 compete for the common binding site, GVYVKM. Thus, by blocking SHP-2 recruitment SAP could function as a negative regulator of CTLA-4. Conclusion: Taken together, our data suggest the existence of complicate signaling cascade in regulating CTLA-4 function, and further provide evidence that SAP can act either as a positive or negative regulator depending on the nature of the associating receptors.

• IMMUNE NETWORK
• /
• 제6권4호
• /
• pp.169-178
• /
• 2006

Background: Adipose tissues were initially introduced as energy storages, but recently they have become famous as an endocrine organ which produces and secretes various kinds of molecules to make physiologic and metabolic changes in human body. It has been studied that these molecules are secreted in abundance as the adipose tissue becomes bigger along with obesity. Furthermore, it has been found that they are mediating systemic inflammation and generation of metabolic diseases such as type 2 diabetes and atherosclerosis. On the basis of these, we studied previous papers which have been researched about the interaction between preadipocytes and macrophages, adipose tissues and lymph nodes, and adipose tissue secreting molecules. Results: Firstly, preadipocytes and macrophages are expressing similar transcriptomes and proteins, and preadipocytes can be converted to mature macrophages which have phagocytic activity. Moreover, the monocytes, which initially located in the bone marrow, are filtrated to the adipose tissue by monocyte chemotatic protein-1 and are matured to macrophages by colony stimulating factor-1. Secondly, adipose tissues and their associated lymph nodes are interacting each other in terms of energy efficiency. Lymph nodes promote lipolysis in adipose tissues, and polyunsaturated fatty acids in adipocytes become energy sources for dendritic cells. Lastly, adipose tissues produce and secrete proinflammatory molecules such as leptin, adiponectin, TNF-${\alpha}$, IL-6, and acute phase proteins, which induce the inflammation and potentially generate metabolic diseases. Conclusion: According to these, we can link adipose tissues to inflammation, but we need to affirm the actual levels and roles of adipose tissue-derived proinflammatory molecules in human body.

• 대한한방부인과학회지
• /
• 제23권2호
• /
• pp.71-84
• /
• 2010

Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.