• Journal of Life Science
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• v.25 no.4
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• pp.473-480
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• 2015

The endoplasmic reticulum (ER) in the eukaryotic cells is the first compartment in the secretory pathway. Almost secretory proteins and membrane proteins are secreted through the ER, in which post-translational modifications occur via diverse signals from the ER lumen to the cytoplasm and nucleus. Only then are correctly-folded proteins secreted to the outside cells. Unfolded proteins that accumulate in the ER cause a kind of intracellular stress, ER stress, and activate an unfolded protein response (UPR) system. The 3 major transducers of the UPR are inositol requiring 1 (IRE1), PKR-like ER kinase (PERK) and activating transcription factor 6 (ATF6), all of which are ER transmembrane proteins. Recently, novel types of a new ATF6 family have been identified. Those commonly have an ER-transmembrane domain, a transcription-activation domain and a basic leucine zipper (bZIP) domain―Luman, OASIS, BBF2H7, CREBH and CREB4. Each factor functions by regulating the UPR in specific organs and tissues. Although the detailed molecular mechanisms of OASIS family members are unknown, in this study we comprehensively introduce these molecular signals.

• Journal of Life Science
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• v.21 no.2
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• pp.328-333
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• 2011

Melatonin has been known as an animal hormone. However, melatonin exists in diverse organisms including higher plants. The biosynthesis and physiological roles for melatonin in plants is still largely unknown, although both dicot and monocot plants have melatonin and some medicinal plants even contain large amounts of melatonin. In this study we detected melatonin in diverse Viola plants, in which melatonin had not been examined so far, by reverse phase HPLC analysis, demonstrating the wide existence of melatonin in the genus of Viola. We then fed tryptophan (Trp) and tryptamine (TAM) to the incubation medium for Viola leaf sections to test their effects on melatonin formation. Trp is also the hypothesized starting material of melatonin in plants, and TAM is the following intermediate produced by the decarboxylation of Trp. Trp feeding did not affect the contents of melatonin. In contrast, TAM feeding clearly increased the level of melatonin in Viola leaves. Because TAM is derived from Trp, we concluded that the Trp-TAM pathway exists in Viola plants as well. Ineffectiveness of Trp feeding to the change of melatonin contents supports the hypothesis that the decarboxylation step from Trp to TAM is the rate-limiting step in plant melatonin biosynthesis.

• Journal of Life Science
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• v.12 no.1
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• pp.87-95
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• 2002

It was observed that the hot water extract of the leaves of Capsicum annuum L., a Korean edible plant, had a potent anti-complementary activity. Crude polysaccharide fraction(CAL-0) was obtained by methanol reflux, ethanol precipitation, dialysis and lyophilization. CAL-0 contained 51.8% of total sugar, 8.2% of uronic acid and 16.8% of protein, and consisted of mainly arabinose, galactose and glucose as neutral sugars and galacturonic acid as uronic acid. The anti-complementary activity of CAL-0 decreased greatly by periodate oxidation, but was not changed by pronase treatment. Also, the anti-complementary activity of CAL-0 was reduced partially in the absence of the $Ca^{2+}$ ion. The crude polysaccharide CAL-0 was found to activate the C3 component both in the presence and in the absence of $Ca^{2+}$ through the crossed-immunoelectrophoresis suggesting that those involved in both classical and alternative complement pathway CAL-0 was further separated to an unabsorbed fraction(CAL-1) and six absorbed fractions(CAL-2longrightarrowCAL-7) on DEAE Sepharose CL-6B ion exchange column. Among them four major fractions in activity and yield were obtained, and consisted mainly of arabinose, galactose and glucose with various molar ratios. The major fraction, CAL-2, was purified to give a high molecular fraction(CAL-2-I) and a low molecular fraction(CAL-2-II) on Sepharose CL-6B column. The anti-complementary activity of CAL-2-I, a molecular weight of about 61,000, was higher than it of CAL-2-II.-II.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.321-330
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• 2021

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

• Journal of Ginseng Research
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• v.47 no.2
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• pp.302-310
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• 2023

Background: The most common type of dementia, Alzheimer's disease (AD), is marked by the formation of extracellular amyloid beta (Aβ) plaques. The impairments of axons and synapses appear in the process of Aβ plaques formation, and this damage could cause neurodegeneration. We previously reported that non-saponin fraction with rich polysaccharide (NFP) from Korean Red Ginseng (KRG) showed neuroprotective effects in AD. However, precise molecular mechanism of the therapeutic effects of NFP from KRG in AD still remains elusive. Methods: To investigate the therapeutic mechanisms of NFP from KRG on AD, we conducted proteomic analysis for frontal cortex from vehicle-treated wild-type, vehicle-treated 5XFAD mice, and NFP-treated 5XFAD mice by using nano-LC-ESI-MS/MS. Metabolic network analysis was additionally performed as the effects of NFP appeared to be associated with metabolism according to the proteome analysis. Results: Starting from 5,470 proteins, 2,636 proteins were selected for hierarchical clustering analysis, and finally 111 proteins were further selected for protein-protein interaction network analysis. A series of these analyses revealed that proteins associated with synapse and mitochondria might be linked to the therapeutic mechanism of NFP. Subsequent metabolic network analysis via genome-scale metabolic models that represent the three mouse groups showed that there were significant changes in metabolic fluxes of mitochondrial carnitine shuttle pathway and mitochondrial beta-oxidation of polyunsaturated fatty acids. Conclusion: Our results suggested that the therapeutic effects of NFP on AD were associated with synaptic- and mitochondrial-related pathways, and they provided targets for further rigorous studies on precise understanding of the molecular mechanism of NFP.

• Journal of Life Science
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• v.18 no.2
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• pp.234-240
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• 2008

Anthocyanin synthesis in strawberry (Fragaria x ananassa cv Maehyang) begins approximately 26 days postflowering and continued throughout fruit ripening. A set of cDNA clones encoding the anthocyanin biosynthetic enzymes were isolated from strawberry. A pair of primers were designed for polymerase chain reaction (PCR) through the comparison of the nucleotide sequences of homologous genes from diverse plants. Reverse transcriptase-PCRs were performed using cDNA synthesized from ripe fruit total RNA and the primers corresponding to each gene. Eight genes of the anthocyanin pathway were cloned and confirmed by sequencing to code for phenylalanine ammonia lyase (PAL), 4-cummarate CoA ligase (4CL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone-3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), anthocyanidine synthase (ANS), UDP-glucose:flavonoid-3-O-glucosyl-transferase (UFGT). Northern analyses showed that the corresponding genes were differentially expressed during the fruit development process. All genes except PAL were predominantly expressed in fruit. Expression of PAL, DFR and ANS was detected 10 days postflowering at the early stage of fruit development, declined for a while and sharply increased 22 days postflowering then showed a peak 34 days postflowering. The other genes, however, were not expressed up to 22 or 30 days postflowering when the initial fruit ripening events occur at the time of initiation of anthocyanin accumulation. The onset of anthocyanin synthesis in ripening strawberry coincides with a coordinated induction of the anthocyanin pathway genes, suggesting the involvement of regulatory genes. We propose that at least two different regulatory mechanisms playa role in the biosynthesis of anthocyanin during color development of strawberry.

• Journal of Marine Life Science
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• v.5 no.2
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• pp.35-42
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• 2020

17β-estradiol (E₂) is a natural hormone secreted by ovary, and continuously discharged from household and livestock wastewater into aquatic environment. Due to its strong estrogenic activity, it has adverse effects on development and reproduction in crustacean as an endocrine disrupting chemical. Although ecdysteroid signaling pathway play a key role in development in crustacean, little information on transcriptional modulation of ecdysteroid-related genes in response to E₂ is available in small crustacean. Here, we investigated the acute toxicity of E₂ to obtain 24-h LC_x values in the brackish water flea Diaphanosoma celebensis. Time-dependent expression patterns of seven ecdysteroid pathway - related genes (CYP314a1, EcRA, EcRB, USP, ERR, Vtg, VtgR) were further examined using quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR). As results, 24-h LC₅₀ and LC₁₀ values were 9.581 mg/l and 4.842 mg/l, respectively. The mRNA expression of CYP314a1, EcRA, USP, VtgR was significantly up-regulated at 12 or 24 h after exposure to E₂. These findings indicate that E₂ can affect their molting and reproduction by modulating the expression of ecdysteroid pathway - related in D. celebensis. This study will be useful for better understanding of molecular mode of action of endocrine disrupting chemicals on molting process in small crustacean.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5339-5343
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• 2012

The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.

• Molecules and Cells
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• v.39 no.11
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• pp.797-806
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• 2016

Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other transcription factors in response to glucose and insulin. The isolated porcine preadipocytes were differentiated into mature adipocytes to investigate the roles and interrelation of these transcription factors in the context of glucose- and insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose-induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed adipocytes irrespective of glucose concentration, suggesting ChREBP mediate glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced lipogenesis. $LXR{\alpha}$ activation promoted lipogenesis and lipogenic genes expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes, $LXR{\alpha}$ activation facilitated lipogenesis and SREBP-1c expression, but had no effect on ChREBP expression. Therefore, $LXR{\alpha}$ might mediate lipogenesis via SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c activation blocked simultaneously, glucose and insulin were still able to stimulated lipogenesis and lipogenic genes expression, and $LXR{\alpha}$ activation enhanced these effects, suggesting $LXR{\alpha}$ mediated directly glucose- and insulin-induced lipogenesis. In summary, glucose and insulin stimulated lipogenesis through both dissimilar and identical regulation pathway in porcine adipocytes.

• Journal of Life Science
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• v.28 no.9
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• pp.999-1006
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• 2018

Obesity is epidemic worldwide and has reportedly been linked to the progression of several metabolic and cardiovascular diseases. The natural products are decreasing the side effects of medicines used for obesity and also have health benefits dut to their numerous bioactive compounds. In this context, Artemisia scoparia is a widespread plant that has been suggested as possessing various types of bioactivity. In this study, the crude extract from A. scoparia (ASE) was tested for its ability to suppress adipogenesis in mouse 3T3-L1 pre-adipocytes. The molecular pathway by which ASE affects differentiation of 3T3-L1 cells was also investigated. The introduction of ASE to differentiating 3T3-L1 pre-adipocytes resulted in suppressed adipogenesis, as confirmed by decreased intracellular lipid accumulation. The differentiating cells treated with 10 and $100{\mu}g/ml$ of ASE showed 21.9 and 29.0% less lipid accumulation, respectively, than untreated adipocytes. In addition, the results indicated that ASE treatment lowered the expression of the adipogenesis-related factors $PPAR{\gamma}$, $C/EBP{\alpha}$, and SREBP-1c. Furthermore, treating with ASE notably decreased levels of phosphorylated p38, ERK, and JNK in 3T3-L1 adipocytes. These results indicate that ASE exhibits significant anti-adipogenesis activity by downregulating the MAPK and $PPAR{\gamma}$ pathways during the differentiation of 3T3-L1 pre-adipocytes. Therefore, A. scoparia may be a potential source of natural products against obesity.