• Herbal Formula Science
• /
• v.32 no.1
• /
• pp.39-49
• /
• 2024

Objectives : The purpose of this study was to investigate the molecular targets and pathways of anti-inflammatory effects of Jakyakgamchotang with corydalis tuber (JC) using network pharmacology. Methods : The compounds in constituent herbal medicines of JC were searched in TCM systems pharmacology (TCMSP). Target gene informations of the components were collected using chemical-target interactions database provided by Pubchem. Afterwards, network analysis between compounds and inflammation-related target genes was performed using cytoscape. Go enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on inflammation-related targets using DAVID database. Results : 70 active compounds related to inflammation were identified, and 295 target genes related to the anti-inflammatory activity of the compound of JC were identified. In the Go biological process DB and KEGG pathway DB, "inflammatory response", "cellular response to lipopolysaccharide", "positive regulation of interleukin-6 production", and "positive regulation of protein kinase B. signaling", "positive regulation of ERK1 and ERK2 cascade", "positive regulation of I-kappaB kinase/NF-kappaB signaling", "negative regulation of apoptotic process", and "PI3K-Akt signaling pathway" were found to be mechanisms related to the anti-inflammatory effects related to the target genes of JC. The main compounds predicted to be involved in the anti-inflammatory effect of JC were quercetin, licochalcone B, (+)-catechin, kaempferol, and emodin. Conclusions : This study provides the molecular targets and potential pathways of JC on inflammation. It can be used as a basic data for using JC for various inflammatory disease in traditional korean medicine clinic.

• Archives of Plastic Surgery
• /
• v.42 no.1
• /
• pp.11-19
• /
• 2015

Background Wound healing is an interaction of a complex signaling cascade of cellular events, including inflammation, proliferation, and maturation. $K^+$ channels modulate the mitogen-activated protein kinase (MAPK) signaling pathway. Here, we investigated whether $K^+$ channel-activated MAPK signaling directs collagen synthesis and angiogenesis in wound healing. Methods The human skin fibroblast HS27 cell line was used to examine cell viability and collagen synthesis after potassium chloride (KCl) treatment by Cell Counting Kit-8 (CCK-8) and western blotting. To investigate whether $K^+$ ion channels function upstream of MAPK signaling, thus affecting collagen synthesis and angiogenesis, we examined alteration of MAPK expression after treatment with KCl (channel inhibitor), NS1619 (channel activator), or kinase inhibitors. To research the effect of KCl on angiogenesis, angiogenesis-related proteins such as thrombospondin 1 (TSP1), anti-angiogenic factor, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), pro-angiogenic factor were assayed by western blot. Results The viability of HS27 cells was not affected by 25 mM KCl. Collagen synthesis increased dependent on time and concentration of KCl exposure. The phosphorylations of MAPK proteins such as extracellular-signal-regulated kinase (ERK) and p38 increased about 2.5-3 fold in the KCl treatment cells and were inhibited by treatment of NS1619. TSP1 expression increased by 100%, bFGF expression decreased by 40%, and there is no significant differences in the VEGF level by KCl treatment, TSP1 was inhibited by NS1619 or kinase inhibitors. Conclusions Our results suggest that KCl may function as a therapeutic agent for wound healing in the skin through MAPK signaling mediated by the $K^+$ ion channel.

• Proceedings of the Korean Society of Plant Pathology Conference
• /
• 2003.10a
• /
• pp.13-13
• /
• 2003

When plants are infected by plant pathogens, rapid cell responses are initiated for further inhibition from fast invasion of pathogens. Hypersensitive response (HR) of plant is well known defense response stopping pathogenesis process through rapid cell death. However, informations on the signaling pathway from reception of pathogen by host plants to appropriate resistant responses are very limited to date. Efficient perception of infection by pathogens and well-programmed signalling mechanism for appropriate responses are important for survival of plants. Plant have developed a sophisticated network(s) of defense/stress responses, among which one of the earliest signalling pathways after perception (of stimuli) is the evolutionary conserved Rop GTPase and mitogen-activated protein kinase (MAPK) cascade.(중략)

• IMMUNE NETWORK
• /
• v.14 no.1
• /
• pp.14-20
• /
• 2014

CD28/T cell receptor ligation activates the NF-${\kappa}B$ signaling cascade during CD4 T cell activation. NF-${\kappa}B$ activation is required for cytokine gene expression and activated T cell survival and proliferation. Recently, many reports showed that NF-${\kappa}B$ activation is also involved in T helper (Th) cell differentiation including Th17 cell differentiation. In this review, we discuss the current literature on NF-${\kappa}B$ activation pathway and its effect on Th17 cell differentiation.

• Biomedical Science Letters
• /
• v.17 no.4
• /
• pp.291-295
• /
• 2011

PD98059 is the specific inhibitor of extracellular signaling-regulated kinase (ERK) kinase (MEK). ERK is involved in a mitogen-activated protein kinase (MAPK) cascade controlling cell growth and differentiation. Although the inhibition of ERK is known to induce cell death in various cell lines, this effect is still controversial and the role of PD98059 on the death of HeLa $S_3$ cells, a subclone of the cervical cancer cell line, is not well understood. The apoptosis of HeLa $S_3$ cells increased after the treatment of 50 ${\mu}M$ PD98059. The induction of apoptosis by PD98059 was occurred in a time- and a dose-dependent manners. The expression of Bcl-2 was reduced in accordance with decrease of ERK2 expression. Taken together, these results indicate that PD98059 has a cytotoxicity in HeLa $S_3$ cells and it may be used as a potential target for the treatment of cervical cancer.

• Molecules and Cells
• /
• v.38 no.7
• /
• pp.651-656
• /
• 2015

Plant growth and development are coordinately orchestrated by environmental cues and phytohormones. Light acts as a key environmental factor for fundamental plant growth and physiology through photosensory phytochromes and underlying molecular mechanisms. Although phytochromes are known to possess serine/threonine protein kinase activities, whether they trigger a signal transduction pathway via an intracellular protein kinase network remains unknown. In analyses of mitogen-activated protein kinase kinase (MAPKK, also called MKK) mutants, the mkk3 mutant has shown both a hypersensitive response in plant hormone gibberellin (GA) and a less sensitive response in red light signaling. Surprisingly, light-induced MAPK activation in wild-type (WT) seedlings and constitutive MAPK phosphorylation in dark-grown mkk3 mutant seedlings have also been found, respectively. Therefore, this study suggests that MKK3 acts in negative regulation in darkness and in light-induced MAPK activation during dark-light transition.

• Clinical and Experimental Pediatrics
• /
• v.54 no.6
• /
• pp.241-245
• /
• 2011

Tuberous sclerosis complex (TSC) is a genetic multisystem disorder that results from mutations in the TSC1 or TSC2 genes, and is associated with hamartomas in several organs, including subependymal giant cell tumors. The neurological manifestations of TSC are particularly challenging and include infantile spasms, intractable epilepsy, cognitive disabilities, and autism. The TSC1- and TSC2-encoded proteins modulate cell function via the mammalian target of rapamycin (mTOR) signaling cascade, and are key factors in the regulation of cell growth and proliferation. The mTOR pathway provides an intersection for an intricate network of protein cascades that respond to cellular nutrition, energy levels, and growth factor stimulation. In the brain, TSC1 and TSC2 have been implicated in cell body size, dendritic arborization, axonal outgrowth and targeting, neuronal migration, cortical lamination, and spine formation. The mTOR pathway represents a logical candidate for drug targeting, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients.

• Proceedings of the Botanical Society of Korea Conference
• /
• 1998.07a
• /
• pp.83-96
• /
• 1998

The plant pigment proteins phytochromes are a molecular light sensor or switch for photomorphogenesis involving a variety of growth and developmental responses of plants to red and far-red wavelength light. Underscoring the photomorphogenesis mediated by phytochromes is the light signal transduction at molecular and cellular levels. For example, a number of genes activated by the phytochrome-mediated signal transduction cascade have been identified and characterized, especially in Arabidopsis thaliana. The light sensor/switch function of phytochromes are based on photochromism of the covalently linked tetrapyrrole chromophore between the two photoreversible forms, Pr and Pfr. The photochromism of phytochromes involves photoisomerization of the tetrapyrrole chromophore. The "photosensor" Pr-form ("switch off" conformation) of phytochromes strongly absorbs 660 nm red light, whereas the "switch on" Pfr-conformation preferentially absorbs 730 nm far-red light. The latter is generally considered to be responsible for eliciting transduction cascades of the red light signal for various responses of plants to red light including positive or negative expression of light-responsive genes in plant nuclei and chloroplasts. In this paper, we discuss the structure-function of phytochromes in plant growth and development, with a few examples of biotechnological implications.

• Journal of Microbiology and Biotechnology
• /
• v.23 no.7
• /
• pp.923-931
• /
• 2013

Rapamycin, known as an inhibitor of Target of Rapamycin (TOR), is an immunosuppressant drug used to prevent rejection in organ transplantation. Despite the close association of the TOR signaling cascade with various scopes of metabolism, it has not yet been thoroughly investigated at the metabolome level. In our current study, we applied mass spectrometric analysis for profiling primary metabolism in order to capture the responsive dynamics of the Chlamydomonas metabolome to the inhibition of TOR by rapamycin. Accordingly, we identified the impact of the rapamycin treatment at the level of metabolomic phenotypes that were clearly distinguished by multivariate statistical analysis. Pathway analysis pinpointed that inactivation of the TCA cycle was accompanied by the inhibition of cellular growth. Relative to the constant suppression of the TCA cycle, most amino acids were significantly increased in a time-dependent manner by longer exposure to rapamycin treatment, after an initial down-regulation at the early stage of exposure. Finally, we explored the isolation of the responsive metabolic factors into the rapamycin treatment and the culture duration, respectively.

• Genomics & Informatics
• /
• v.7 no.1
• /
• pp.26-31
• /
• 2009

Heat shock proteins are a class of molecular chaperones that can be found in nearly all organisms from Bacteria, Archaea and Eukarya domains. Heat shock proteins experience increased transcription during periods of heat induced osmotic stress and are involved in protein disaggregation and refolding as part of a cell's danger signaling cascade. Heat shock protein, Hsp20 is a small molecular chaperone that is approximately 20kDa in weight and is hypothesized to prevent aggregation and denaturation. Hsp20 can be found in several strains of Proteobacteria, which comprises the largest phyla of the Bacteria domain and also contains several medically significant bacterial strains. Genomic analyses were performed to determine a common evolutionary pattern among Hsp20 sequences in Proteobacteria. It was found that Hsp20 shared a common ancestor within and among the five subclasses of Proteobacteria. This is readily apparent from the amount of sequence similarities within and between Hsp20 protein sequences as well as phylogenetic analysis of sequences from proteobacterial and non-proteobacterial species.