• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.348-353
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• 2005

In this paper we discuss the formulation and the analysis of a signaling pathway by Petri nets. In order to explicitly and formally describe the molecular mechanisms and pathological characteristics of signaling pathways, we propose a new modeling method to construct signaling pathways on the basis of formal representation of Petri net. Our proposed extended algorithm effectively finds basic enzymic components of signaling pathways by employing T-invariants of Petri nets with considering the origination leading to an occurrence of inhibition functions than existing methods. An application of the proposed algorithm is given with the example of Interleukin-1 and Interleukin-6 signaling pathways.

• BMB Reports
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• v.47 no.7
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• pp.361-368
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• 2014

Lipid components in biological membranes are essential for maintaining cellular function. Phosphoinositides, the phosphorylated derivatives of phosphatidylinositol (PI), regulate many critical cell processes involving membrane signaling, trafficking, and reorganization. Multiple metabolic pathways including phosphoinositide kinases and phosphatases and phospholipases tightly control spatio-temporal concentration of membrane phosphoinositides. Metabolizing enzymes responsible for PI 4,5-bisphosphate (PI(4,5)P2) production or degradation play a regulatory role in Toll-like receptor (TLR) signaling and trafficking. These enzymes include PI 4-phosphate 5-kinase, phosphatase and tensin homolog, PI 3-kinase, and phospholipase C. PI(4,5)P2 mediates the interaction with target cytosolic proteins to induce their membrane translocation, regulate vesicular trafficking, and serve as a precursor for other signaling lipids. TLR activation is important for the innate immune response and is implicated in diverse pathophysiological disorders. TLR signaling is controlled by specific interactions with distinct signaling and sorting adaptors. Importantly, TLR signaling machinery is differentially formed depending on a specific membrane compartment during signaling cascades. Although detailed mechanisms remain to be fully clarified, phosphoinositide metabolism is promising for a better understanding of such spatio-temporal regulation of TLR signaling and trafficking.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4405-4409
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• 2014

Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions. The human body has several mechanisms to counteract oxidative stress by producing antioxidants. A shift in the balance between oxidants and antioxidants in favor of oxidants is termed as "oxidative stress". Paradoxically, there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2). This review also deals with classification as well as mechanisms of formation of free radicals, examining their beneficial and deleterious effects on cellular activities and focusing on the potential role of antioxidants in preventing and repairing damage caused by oxidative stress. A discussion of the role of phytochemical antioxidants in oxidative stress, disease and the epigenome is included.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.115-122
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• 2016

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

• Journal of the Institute of Electronics Engineers of Korea TC
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• v.41 no.9
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• pp.55-65
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• 2004

ATM was recommended by the ITU and ATM Forum as a means of transportation for B-ISDN. At this time, due to the comprehensive mature of ATM protocol, ATM has been adapted as the backbone system for carrying Internet traffi $c^{[1,2,3,4]}$. But major conceptsregarding the ATN protocol will be used on future technology. This paper presents preventive congestion control mechanisms for detecting HTR(Hard-To Reach) code in ATM systems, in particular for an improved HTR call registration method using network signaling information will discussed. In high speed circuit switching system environments, a fast HTR control mechanism is necessary. We present research results for improving HTR call registration and control methods using network signaling information and fuzzy control mechanisms. We concluded that it showed fast congestion avoidance mechanisms with a fewer system load maximized the efficiency of network resources by restricting ineffective machine attempts.

• BMB Reports
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• v.53 no.12
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• pp.640-645
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• 2020

Suppressors of cytokine signaling (SOCS) exhibit diverse anti-inflammatory effects. Since ROS acts as a critical mediator of inflammation, we have investigated the anti-inflammatory mechanisms of SOCS via ROS regulation in monocytic/macrophagic cells. Using PMA-differentiated monocytic cell lines and primary BMDMs transduced with SOCS1 or shSOCS1, the LPS/TLR4-induced inflammatory signaling was investigated by analyzing the levels of intracellular ROS, antioxidant factors, inflammasome activation, and pro-inflammatory cytokines. The levels of LPS-induced ROS and the production of pro-inflammatory cytokines were notably down-regulated by SOCS1 and up-regulated by shSOCS1 in an NAC-sensitive manner. SOCS1 up-regulated an ROS-scavenging protein, thioredoxin, via enhanced expression and binding of NRF-2 to the thioredoxin promoter. SOCS3 exhibited similar effects on NRF-2/thioredoxin induction, and ROS downregulation, resulting in the suppression of inflammatory cytokines. Notably thioredoxin ablation promoted NLRP3 inflammasome activation and restored the SOCS1-mediated inhibition of ROS and cytokine synthesis induced by LPS. The results demonstrate that the anti-inflammatory mechanisms of SOCS1 and SOCS3 in macrophages are mediated via NRF-2-mediated thioredoxin upregulation resulting in the downregulation of ROS signal. Thus, our study supports the anti-oxidant role of SOCS1 and SOCS3 in the exquisite regulation of macrophage activation under oxidative stress.

• The Korea Journal of Herbology
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• v.38 no.6
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• pp.73-91
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• 2023

Objectives : This study used a network pharmacology approach to elucidate the efficacy and molecular mechanisms of Daehwangmokdanpitang (DHMDPT) on Psoriasis. Methods : Using OASIS databases and PubChem database, compounds of DHMDPT and their target genes were collected. The putative target genes of DHMDPT and known target genes of psoriasis were compared and found the correlation. Then, the network was constructed using Cytoscape 3.10.1. The key target genes were screened by Analyzer network and their functional enrichment analysis was conducted based on the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathways to predict the mechanisms. Results : The result showed that total 30 compounds and 439 related genes were gathered from DHMDPT. 264 genes were interacted with psoriasis gene set, suggesting that the effects of DHMDPT are closely related to psoriasis. Based on GO enrichment analysis and KEGG pathways, 'Binding', 'Cytokine Activity', 'Receptor Ligand Activity' 'HIF-1 signaling pathway', 'IL-17 signaling pathway', 'Toll-like receptor signaling pathway', and 'TNF signaling pathway' were predicted as functional pathways of 16 key target genes of DHMDPT on psoriasis. Among the target genes, IL6, IL1B, TNF, AKT1 showed high correlation with the results of KEGG pathways. Additionally, Emodin, Acetovanillone, Gallic acid, and Ferulic acid showed a high relevance with key genes and their mechanisms. Conclusion : Through a network pharmacological method, DHMDPT was predicted to have high relevance with psoriasis. This study could be used as a basis for studying therapeutic effects of DHMDPT on psoriasis.

• Proceedings of the Zoological Society Korea Conference
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• 1999.04a
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• pp.36-36
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• 1999

No Abstract, See Full Text

• Molecules and Cells
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• v.26 no.5
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• pp.503-513
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• 2008

The vomeronasal organ (VNO) is a sensory organ that influences social and/or reproductive behavior and, in many cases, the survival of an organism. The VNO is believed to mediate responses to pheromones; however, many mechanisms of signal transduction in the VNO remain elusive. Here, we examined the expression of proteins involved in signal transduction that are found in the main olfactory system in the VNO. The localization of many signaling molecules in the VNO is quite different from those in the main olfactory system, suggesting differences in signal transduction mechanisms between these two chemosensory organs. Various signaling molecules are expressed in distinct areas of VNO sensory epithelium. Interestingly, we found the expressions of groups of these signaling molecules in glandular tissues adjacent to VNO, supporting the physiological significance of these glandular tissues. Our finding of high expression of signaling proteins in glandular tissues suggests that neurohumoral factors influence glandular tissues to modulate signaling cascades that in turn alter the responses of the VNO to hormonal status.

• BMB Reports
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• v.51 no.3
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• pp.143-150
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• 2018

The Hippo signaling pathway plays an essential role in adult tissue homeostasis and organ size control. Abnormal regulation of Hippo signaling can be a cause for multiple types of human cancers. Since the awareness of the importance of the Hippo signaling in a wide range of biological fields has been continually grown, it is also understood that a thorough and well-rounded comprehension of the precise dynamics could provide fundamental insights for therapeutic applications. Several components in the Hippo signaling pathway are known to be targeted for proteasomal degradation via ubiquitination by E3 ligases. ${\beta}-TrCP$ is a well-known E3 ligase of YAP/TAZ, which leads to the reduction of YAP/TAZ levels. The Hippo signaling pathway can also be inhibited by the E3 ligases (such as ITCH) which target LATS1/2 for degradation. Regulation via ubiquitination involves not only complex network of E3 ligases but also deubiquitinating enzymes (DUBs), which remove ubiquitin from its targets. Interestingly, non-degradative ubiquitin modifications are also known to play important roles in the regulation of Hippo signaling. Although there has been much advanced progress in the investigation of ubiquitin modifications acting as regulators of the Hippo signaling pathway, research done to date still remains inadequate due to the sheer complexity and diversity of the subject. Herein, we review and discuss recent developments that implicate ubiquitin-mediated regulatory mechanisms at multiple steps of the Hippo signaling pathway.