• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.431-437
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• 2011

Aberrant activation of microglia has been reported to cause neuronal damages by releasing a variety of pro-inflammatory cytokines. Besides where microglia become active, damages have been also observed in remote places, which is considered due to the migration of activated microglia. Therefore, an agent that could suppress abnormal activation of microglia and their subsequent migration might be valuable in activated microglia-related brain pathologies. The objective of the present study was to evaluate anti-inflammatory effects of betulinic acid on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of betulinic acid significantly attenuated LPS-induced NO production and protein expression of iNOS. Betulinic acid also significantly suppressed LPS-induced release and expression of cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. Furthermore, betulinic acid significantly uppressed LPS-induced MMP-9 expression, which has been suggested to play an important role in the migration of activated microglia. In order to understand the possible mechanism by which betulinic acid suppresses LPS-induced cytokine production and migration of microglia, the role of NF-kB, a major pro-inflammatory transcription factor, was examined. Betulinic acid significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB upon LPS stimulation was significantly suppressed with betulinic acid. Taken together, the present study for the first time demonstrates that betulinic acid possesses anti-inflammatory activity through the suppression of nuclear translocation of NF-kB in BV2 microglial cells.

• Journal of Life Science
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• v.26 no.7
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• pp.868-874
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• 2016

Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are members of the serine or threonine protein kinase superfamily that phosphorylates the hydroxyl group of serine or threonine through the highly conserved kinase region. The RIPK family plays a crucial role not only in inflammation and innate immunity, but also in mediating programmed cell death, such as apoptosis and necroptosis. The interaction between RIPK1 and other TNFR1-related proteins has been shown to assemble a signaling complex I that controls activation of the pro-survival transcription factor NF-κB upon binding of cytokines to TNF receptor 1 (TNFR1). Moreover, RIPK1 and RIPK3 interact through their RIP homotypic interaction motifs (RHIMs) to mediate programmed necrosis, which has long been considered an accidental and uncontrolled cell death form with morphological characteristics differing from those of apoptosis. Highly conserved sequences of RHIM in RIPK1 and RIPK3 were shown to regulate their binary interaction, leading to assembly of a cytosolic amyloid complex termed the “necrosome”. The necrosome also contains mixed lineage kinase domain-like protein (MLKL), which has been found recently to be a substrate of RIPK3 to mediate downstream signaling. This review provides an overview of the functional and physiological characteristics of RIPKs and MLKL in TNF signaling.

• Journal of Life Science
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• v.22 no.3
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• pp.417-427
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• 2012

We compared the transcriptome in response to propanol stress in wild-type and propanol-resistant mutant Escherichia coli using the DNA microarray technique. The correlation value of RNA expression between the propanol-treated wild type and the untreated-one was about 0.949, and 50 genes were differentially expressed by more than twofold in both samples. The correlation value of RNA expression between the propanol-treated mutant and the untreated one was about 0.951, and 71 genes in two samples showed differential expression patterns. However, the values between the wild type and mutant, regardless of propanol addition, were 0.974-0.992 and only 1-2 genes were differentially expressed in the two strains. The representative characteristics among differentially expressed genes in W3110 or P19 treated with propanol compared to untreated samples were up-regulation of hest shock response genes and down-regulation of genes relating to ribosome biosynthesis. In addition, many genes were regulated by transcription regulation factors such as ArcA, CRP, FNR, H-NS, GatR, or PurR and overexpressed by sigma factor RpoH. We confirmed that RpoH mediated an important host defense function in propanol stress in E. coli W3110 and P19 by comparison of cell growth rate among the wild type, rpoH disruptant mutant, and rpoH-complemented strain.

• Journal of Life Science
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• v.22 no.3
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• pp.360-365
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• 2012

We investigated the anti-proliferative activity of sulforaphane and expression changes of NAG-1 and p21 genes in response to sulforaphane treatment in human colorectal HCT116 cells. The results showed that sulforaphane decreased cell viabilities in a dose-dependent manner and induced expression of NAG-1 and p21 proteins in a dose-dependent and time-dependent manner. In addition, we found that NAG-1 expression by sulforaphane was not dependent on the presence of p53, whereas p21 expression was dependent on p53 presence. The results indicated that up-regulation of NAG-1 was not related with the activity of a dietary histone deacetylase inhibitor of sulforaphane. ATF3 induction was detected from 2 hr after sulforaphane treatment, indicating that ATF3 could be a transcription factor to up-regulate NAG-1 expression. The results of this study may help to increase our understanding of the molecular mechanism of anti-cancer activity mediated by sulforaphane in human colorectal cancer cells.

• Korean Journal of Food Science and Technology
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• v.50 no.1
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• pp.105-110
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• 2018

Melittin is the main component of apitoxin (bee venom) that has been reported to have anti-inflammatory and anti-cancer effects. Herein, we demonstrated that inhibition of epithelial-mesenchymal transition (EMT) by melittin causes suppression of cancer cell migration and invasion. Melittin significantly suppressed the epidermal growth factor (EGF)-induced cell migration and invasion in lung cancer cells. Moreover, melittin up-regulated the expression of epithelial marker protein, E-cadherin, and down-regulated the expression of EMT related proteins, vimentin and fibronectin. Mechanistic studies revealed that melittin markedly suppressed the expression of EMT mediated transcription factors, ZEB2, Slug, and Snail. The EGF-induced phosphorylation of AKT, mTOR, P70S6K, and 4EBP1 was also inhibited by melittin, but not that of ERK and JNK. Therefore, the inhibitory effect of melittin on migration and invasion of lung cancer cells may be associated with the inhibition of EMT via blocking of the AKT-mTOR-P70S6K-4EBP1 pathway.

• BMB Reports
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• v.52 no.10
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• pp.595-600
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• 2019

Cardiac fibrosis is a common feature in chronic hypertension patients with advanced heart failure, and endothelial-to-mesenchymal transition (EndMT) is known to promote Angiotensin II (Ang II)-mediated cardiac fibrosis. Previous studies have suggested a potential role for the transcription factor, ETS-1, in Ang II-mediated cardiac remodeling, however the mechanism are not well defined. In this study, we found that mice with endothelial Ets-1 deletion showed reduced cardiac fibrosis and hypertrophy following Ang II infusion. The reduced cardiac fibrosis was accompanied by decreased expression of fibrotic matrix genes, reduced EndMT with decreased Snail, Slug, Twist, and ZEB1 expression, as well as reduced cardiac hypertrophy and expression of hypertrophy-associated genes was observed. In vitro studies using cultured H5V cells further confirmed that ETS-1 knockdown inhibited $TGF-{\beta}1$-induced EndMT. This study revealed that deletion of endothelial Ets-1 attenuated Ang II-induced cardiac fibrosis via inhibition of EndMT, indicating an important ETS-1 function in mediating EndMT. Inhibition of ETS-1 could be a potential therapeutic strategy for treatment of heart failure secondary to chronic hypertension.

• Journal of Life Science
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• v.29 no.11
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• pp.1200-1207
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• 2019

Ultraviolet radiation exposure is a major cause of extrinsic skin aging, which leads to skin hyperpigmentation. Loganin, a major iridoid glycoside obtained from Corni fructus, has anti-inflammatory, anti-diabetic, and neuroprotective effects. In this study, we investigated the mechanisms underlying the anti-melanogenic effects of loganin in B16F10 melanocytes treated with ${\alpha}$-melanocyte stimulating hormone (${\alpha}-MSH$) and 3-isobutyl-1-methylxanthine (IBMX). Anti-melanogenic activity was measured by treating cells with loganin at concentrations between 1 and $20{\mu}m$. Cell viability assays confirmed that doses of loganin up to $20{\mu}m$ were not cytotoxic. Loganin significantly and dose-dependently decreased intracellular melanin production. We also investigated potential molecular signaling pathways for the anti-melanogenesis effects of loganin. Western blotting showed that treatment with ${\alpha}-MSH$ and IBMX increased the phosphorylation of cAMP response element-binding protein (CREB) and the gene expressions of microphthalmia-associated transcription factor (MITF) and tyrosinase. Addition of loganin suppressed these increases, while promoting the phosphorylation of extracellular signal regulated kinase (ERK) and the anti-melanogenesis response. Our data therefore indicated that loganin could attenuate the increased melanin synthesis induced by ${\alpha}-MSH$ and IBMX treatment of B16F10 melanocytes. This attenuation appears to occur by downregulation of CREB phosphorylation and MITF and tyrosinase gene expression and upregulation of ERK phosphorylation. These finding suggests that loganin could be a valuable candidate for treatment of skin diseases related to hyperpigmentation.

• Korean Journal of Acupuncture
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• v.38 no.3
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• pp.140-150
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• 2021

Objectives : The increase of osteoclasts could cause osteoporosis and bone-related diseases. Also, the inhibition of osteoclast differentiation is important in treating bone-related diseases. Traditionally, Psoraleae Semen has been used for geriatric diseases, aging and musculoskeletal diseases. The purpose of this study is to investigate the effect of Psoraleae Semen ethanol extract (PS) on osteoclast differentiation and its function. Methods : To confirm the effect of PS on osteoclastogenesis and bone resorption activity, various levels of concentrations of PS (5, 10, 20 and 40 ㎍/ml) were tested on RAW 264.7 cells cultured with RANKL. We measured tartarate-resistant acid phosphatase (TRAP)-positive cells, TRAP activity, pit formation and F-actin ring formation. The expressions of nuclear factor of activated T-cells (NFATc1) and c-Fos were confirmed through western blot and reverse transcription- polymerase chain reaction (RT-PCR). Also, the expression of bone resorption and fusion-related genes in osteoclast was confirmed by RT-PCR. Results : PS decreased the number of TRAP-positive cells and the TRAP activity. In addition, PS significantly inhibited the formation of pit and F-actin ring. Furthermore, PS decreased the expression of osteoclast related genes. Conclusions : PS inhibits osteoclast differentiation and bone resorption ability through inhibition of the expression of osteoclast-related genes. This indicates that PS may be a potential therapeutic agent to osteoporosis by suppressing osteoclastogenesis.

• The Korean Journal of Mycology
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• v.49 no.4
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• pp.487-495
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• 2021

Lentinula edodes is a tetrapolar basidiomycete and its mating type is determined by two unlinked genetic loci, A and B. Theoretically, one dikaryotic strain could produce basidiospores with four different mating types in a 1:1:1:1 ratio. Previous studies have described the skewed segregation ratio of mating types among basidiospores of L. edodes. However, they were based only on morphological characteristics, such as clamp connection, to determine mating types. To clarify whether the segregation distortion of mating types is a general phenomenon in L. edodes, we analyzed the mating types of basidiospores obtained from three cultivars of L. edodes using recently developed DNA markers. We found that the skewed segregation of mating types was strain-specific, as reported previously. Among the three cultivars, one cultivar showed balanced segregation, while the other two displayed distorted segregation. We also examined the relationship between mating type and mycelial growth rate of monokaryons derived from each basidiospore. It was found that the monokaryotic mycelial growth rate was related to the A mating type but not to the B mating type. Therefore, homeodomain transcription factor genes that reside on the A locus or other genes linked to the A locus affect the growth rate of monokaryotic mycelia. Considering the importance of mating types in mushroom breeding, this study is informative for establishing an efficient breeding strategy as well as for understanding the mechanism of monokaryotic mycelial growth.

• Korean Journal of Breeding Science
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• v.40 no.4
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• pp.387-393
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• 2008

Over 7 individual rice (Oryza sativa L.) plants per a line were sowed and sampled by pooled sampling method for genomic DNA extraction. The 5,400 flanking sequence tags (FSTs) were analysed by adaptor PCR and direct sequencing. FST analysis showed that the intragenic FSTs, the intergenic FSTs, and the original insertional sequences including hot spot covered 48.1% (2,597), 25.6% (1,383), and 25% (1,350), respectively. The 2,597 intragenic FSTs were used for genotyping to determine whether they are heterozygous or homozygous, and 1,393 core lines were selected. Among them, 422 knockout genes were distributed on chromosome 3, while 56 - 157 intragenic FSTs scattered on other chromosomes. Among 1,393 FSTs, known genes such as transcription factor covered 59.4% (827), while unknown genes such as expressed protein covered 40.6% (566). RT-PCR indicated that some core lines had no expression or decreased expression level in their knockout genes. It means that core lines are very useful knockout lines for functional genomic studies.