• Title/Summary/Keyword: signal pathways

Search Result 566, Processing Time 0.02 seconds

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Activates Pro-Survival Signaling Pathways, Nuclear Factor-${\kappa}B$ and Extracellular Signal-Regulated Kinase 1/2 in Trophoblast Cell Line, JEG-3

  • Ka Hakhyun
    • Reproductive and Developmental Biology
    • /
    • v.29 no.2
    • /
    • pp.101-108
    • /
    • 2005
  • Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a well-known inducer of apoptotic cell death in many tumor cells. 1RAIL is expressed in human placenta, and cytotrophoblast cells express 1RAIL receptors. However, the role of TRAIL in human placentas and cytotrophoblast cells is not. well understood. In this study a trophoblast cell line, JEG-3, was used as a model system to examine the effect of TRAIL. on key intracellular signaling pathways involved in the control of trophoblastic cell apoptosis and survival JEG-3 cells expressed receptors for 1RAIL, death receptor (DR) 4, DR5, decoy receptor (OcR) 1 and DeR2. Recombinant human TRAIL (rhTRAIL) did not have a cytotoxic effect determined by MIT assay and did not induce apoptotic cell death determined by poly-(ADP-ribose) polymerase cleavage assay. rhTRAIL induced a rapid and transient nuclear translocation of nuclear $factor-{\kappa}B(NF-{\kappa}B)$ determined by immunoblotting using nuclear protein extracts. rhTRAIL rapidly activated extracellular signal-regulated protein kinase (ERK) 1/2 as determined by immnoblotting for phospho-ERK1/2. However, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38MAPK) and Akt (protein kinase B) were not activated by rhTRAIL. The ability of 1RAIL to induce $NF-{\kappa}B$ and ERK1/2 suggests that interaction between TRAIL and its receptors may play an important role in trophoblast cell function during pregnancy.

Identifying Statistically Significant Gene-Sets by Gene Set Enrichment Analysis Using Fisher Criterion (Fisher Criterion을 이용한 Gene Set Enrichment Analysis 기반 유의 유전자 집합의 검출 방법 연구)

  • Kim, Jae-Young;Shin, Mi-Young
    • Journal of the Institute of Electronics Engineers of Korea CI
    • /
    • v.45 no.4
    • /
    • pp.19-26
    • /
    • 2008
  • Gene set enrichment analysis (GSEA) is a computational method to identify statistically significant gene sets showing significant differences between two groups of microarray expression profiles and simultaneously uncover their biological meanings in an elegant way by employing gene annotation databases, such as Cytogenetic Band, KEGG pathways, gene ontology, and etc. For the gone set enrichment analysis, all the genes in a given dataset are first ordered by the signal-to-noise ratio between the groups and then further analyses are proceeded. Despite of its impressive results in several previous studies, however, gene ranking by the signal-to-noise ratio makes it difficult to consider highly up-regulated genes and highly down-regulated genes at the same time as the candidates of significant genes, which possibly reflect certain situations incurred in metabolic and signaling pathways. To deal with this problem, in this article, we investigate the gene set enrichment analysis method with Fisher criterion for gene ranking and also evaluate its effects in Leukemia related pathway analyses.

Roles of mTOR and p-mTOR in Gastrointestinal Stromal Tumors

  • Li, Jun-Chuan;Zhu, Hong-Yu;Chen, Ting-Xuan;Zou, Lan-Ying;Wang, Xiao-Yan;Zhao, Hui-Chuan;Xu, Jun
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.14 no.10
    • /
    • pp.5925-5928
    • /
    • 2013
  • Objective: This study aimed to examine the relationship between expression of mammal target of rapamycin (mTOR) and phosphorylation of mTOR (p-mTOR) protein in the PI3K/Akt/mTOR signaling pathways in gastrointestinal stromal tumors and relatiuonships with clinical factors. Methods: Immunohistochemistry was used to detect the expression of the associated proteins mTOR, p-mTOR, and phosphorylation of the tumor suppressor genes PTEN, P27, VEGF, and EGFR in 40 cases of gastrointestinal stromal tumors, with division into a very low and low risk group as well as a moderate and high risk group. Results: The positive rate of mTOR and p-mTOR was significantly increased in the moderate and high risk group compared with the very low and low risk group. The difference was statistically significant (P<0.05). When grouped according to size, the positive mTOR expression rate exhibited a statistical difference (P<0.05), which was significantly increased in the group of tumors larger than 5 cm. The difference in the positive mTOR and p-mTOR expression rate exhibit no statistical significance among the PTEN, P27, VEGF, and EGFR expression subgroups (P>0.05). Conclusion: The different expressions of mTOR and p-mTOR in the signal transduction pathway of gastrointestinal stromal tumor in the different degree-of-risk groups suggested that the mTOR and p-mTOR of the signal transduction pathway serve an important function in the occurrence and development of gastrointestinal stromal tumors.

Development and Characterization of a Novel Anti-idiotypic Monoclonal Antibody to Growth Hormone, Which Can Mimic Physiological Functions of Growth Hormone in Primary Porcine Hepatocytes

  • Lan, Hai-Nan;Jiang, Hai-Long;Li, Wei;Wu, Tian-Cheng;Hong, Pan;Li, Yu Meng;Zhang, Hui;Cui, Huan-Zhong;Zheng, Xin
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.28 no.4
    • /
    • pp.573-583
    • /
    • 2015
  • B-32 is one of a panel of monoclonal anti-idiotypic antibodies to growth hormone (GH) that we developed. To characterize and identify its potential role as a novel growth hormone receptor (GHR) agonist, we determined that B-32 behaved as a typical $Ab2{\beta}$ based on a series of enzyme-linked immunosorbent assay assays. The results of fluorescence-activated cell sorting, indirect immunofluorescence and competitive receptor binding assays demonstrated that B-32 specifically binds to the GHR expressed on target cells. Next, we examined the resulting signal transduction pathways triggered by this antibody in primary porcine hepatocytes. We found that B-32 can activate the GHR and Janus kinase (2)/signal transducers and activators of transcription (JAK2/STAT5) signalling pathways. The phosphorylation kinetics of JAK2/STAT5 induced by either GH or B-32 were analysed in dose-response and time course experiments. In addition, B32 could also stimulate porcine hepatocytes to secrete insulin-like growth factors-1. Our work indicates that a monoclonal anti-idiotypic antibody to GH (B-32) can serve as a GHR agonist or GH mimic and has application potential in domestic animal (pig) production.

BIRB 796 has Distinctive Anti-inflammatory Effects on Different Cell Types

  • Ryoo, Soyoon;Choi, Jida;Kim, Jaemyung;Bae, Suyoung;Hong, Jaewoo;Jo, Seunghyun;Kim, Soohyun;Lee, Youngmin
    • IMMUNE NETWORK
    • /
    • v.13 no.6
    • /
    • pp.283-288
    • /
    • 2013
  • The pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF${\alpha}$) and interleukin (IL)-$1{\beta}$ are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-${\kappa}B$) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.

Expression profiling of cultured podocytes exposed to nephrotic plasma reveals intrinsic molecular signatures of nephrotic syndrome

  • Panigrahi, Stuti;Pardeshi, Varsha Chhotusing;Chandrasekaran, Karthikeyan;Neelakandan, Karthik;PS, Hari;Vasudevan, Anil
    • Clinical and Experimental Pediatrics
    • /
    • v.64 no.7
    • /
    • pp.355-363
    • /
    • 2021
  • Background: Nephrotic syndrome (NS) is a common renal disorder in children attributed to podocyte injury. However, children with the same diagnosis have markedly variable treatment responses, clinical courses, and outcomes, suggesting molecular heterogeneity. Purpose: This study aimed to explore the molecular responses of podocytes to nephrotic plasma to identify specific genes and signaling pathways differentiating various clinical NS groups as well as biological processes that drive injury in normal podocytes. Methods: Transcriptome profiles from immortalized human podocyte cell line exposed to the plasma of 8 subjects (steroid-sensitive nephrotic syndrome [SSNS], n=4; steroid-resistant nephrotic syndrome [SRNS], n=2; and healthy adult individuals [control], n=2) were generated using microarray analysis. Results: Unsupervised hierarchical clustering of global gene expression data was broadly correlated with the clinical classification of NS. Differential gene expression (DGE) analysis of diseased groups (SSNS or SRNS) versus healthy controls identified 105 genes (58 up-regulated, 47 down-regulated) in SSNS and 139 genes (78 up-regulated, 61 down-regulated) in SRNS with 55 common to SSNS and SRNS, while the rest were unique (50 in SSNS, 84 genes in SRNS). Pathway analysis of the significant (P≤0.05, -1≤ log2 FC ≥1) differentially expressed genes identified the transforming growth factor-β and Janus kinase-signal transducer and activator of transcription pathways to be involved in both SSNS and SRNS. DGE analysis of SSNS versus SRNS identified 2,350 genes with values of P≤0.05, and a heatmap of corresponding expression values of these genes in each subject showed clear differences in SSNS and SRNS. Conclusion: Our study observations indicate that, although podocyte injury follows similar pathways in different clinical subgroups, the pathways are modulated differently as evidenced by the heatmap. Such transcriptome profiling with a larger cohort can stratify patients into intrinsic subtypes and provide insight into the molecular mechanisms of podocyte injury.

Plant abscission: An age-old yet ongoing challenge in future agriculture (탈리 신호전달의 메커니즘에 대한 최신 연구동향 및 미래 농업의 적용 방안)

  • Jinsu Lee
    • Journal of Plant Biotechnology
    • /
    • v.50
    • /
    • pp.142-154
    • /
    • 2023
  • Plant abscission is a natural process in which plant organs or tissues undergo detachment, a strategy selected by nature for the disposal of nonessential organs and widespread dissemination of seeds and fruits. However, from an agricultural perspective, the abscission of seeds or fruits represents a major factor that reduces crop productivity and product quality. Therefore, during the crop domestication process in traditional agriculture, mutants exhibiting suppressed abscission were selected and crossbred, thereby enabling the production of modern crop varieties such as rice, tomatoes, canola, and soybeans. These crops possess a unique trait of retaining ripe fruits or seeds in contrast to disposal via abscission. During the previous century, research on quantitative trait loci along with genetic and molecular biological studies on Arabidopsis thaliana have elucidated various cell biological mechanisms, signaling pathways, and transcription regulators involved in abscission. Additionally, it has been revealed that various hormone signals, which are involved in plant growth, play crucial roles in modulating abscission activity. Researchers have developed several chemical treatments that target these hormones and signal transduction pathways to enhance crop yields. This review aimed to introduce the previously identified signal transduction pathways and pivotal regulators implicated in abscission activity. Moreover, this review will discuss the future direction of research required to investigate crop abscission mechanisms for their potential application in smart farming and other areas of agriculture, as well as areas within model systems that require extensive research.