• KSBB Journal
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• v.24 no.3
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• pp.227-238
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• 2009

In the recent years, some organic toxic chemicals were used for obtaining high-yield productivity in agriculture. The undegraded pesticides may remain in the agricultural foods through atmosphere, water, and soil and cause public health problems to environmental resources and human beings even at very low concentrations. Small amounts of pesticides can affect a central nervous system, resulting in immunogenic diseases, infertility problems, respiratory diseases and born marrow diseases, which can lead even to death. Monitoring of the environmental pesticide is one of the important issues for the human well-being. Several kinds of biosensors have been successfully applied to the detection of agrichemical toxicity. Also, few platforms for biocide detection have been definitely developed for the degradation and reaction of pesticides. Biochip and electrochemistry experiments involve immobilizing a receptor molecule on a solid substrate surface, and monitoring its interaction with an analyze in a sample solution. Furthermore, nanotechnology can be applied to make high-throughput analyses that are smaller, faster and sensitive than conventional assays. Some nanomaterials or nanofabricated surfaces can be coupled to biomolecules and used in antibody-based assays and enzymatic methods for pesticide residues. The operation procedure has become more convenient as it does not require labeling procedure. In this paper, we review the recent advances in agrichemical defection research and also describe the label-free biosensor for pesticides using various useful detection methods.

• Journal of Life Science
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• v.23 no.7
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• pp.926-932
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• 2013

Glutamine and serum are essential for cell survival and proliferation in vitro, yet the signaling pathways that sense glutamine and serum levels in endothelial cells remain uninvestigated. In this study, we examined the effects of glutamine deprivation and serum starvation on the fate of endothelial cells using a human umbilical vein endothelial cell (HUVEC) model. Our data indicated that glutamine deprivation and serum starvation trigger a progressive reduction in cell viability through apoptosis induction in HUVECs as determined by DAPI staining and flow cytometry analysis. Although the apoptotic effects were more predominant in the glutamine deprivation condition, both apoptotic actions were associated with an increase in the Bax/Bcl-2 (or Bcl-xL) ratio, down-regulation of the inhibitor of apoptosis protein (IAP) family proteins, activation of caspase activities, and concomitant degradation of poly (ADP-ribose) polymerases. Moreover, down-regulation of the expression of Bid or up-regulation of truncated Bid (tBid) were observed in cells grown under the same conditions, indicating that glutamine deprivation and serum starvation induce the apoptosis of HUVECs through a signaling cascade involving death-receptor-mediated extrinsic pathways, as well as mitochondria-mediated intrinsic caspase pathways. However, apoptosis was not induced in cells grown in glutamine- and serum-free media when compared with cells exposed to glutamine deprivation or serum starvation alone. Taken together, our data indicate that glutamine deprivation and serum starvation suppress cell viability without apoptosis induction in HUVECs.

• Journal of Life Science
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• v.23 no.4
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• pp.518-528
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• 2013

Scutellaria baicalensis, belonging to the family Labiatae, is widely distributed in Korea, China, Mongolia, and eastern Siberia. It has been used in traditional medicine for various diseases, such as dysentery, pyrexia, jaundice, and carbuncles. In addition, S. baicalensis is reported to possess various beneficial pharmacological activities, including anti-inflammatory, antidiabetic, antiviral, antihypertension, antioxidant, and anticancer effects. However, the molecular mechanisms of its anticancer activity have not been clearly elucidated. In the present study, we investigated the proapoptotic effects of ethanol extract of S. baicalensis (EESB) on human renal cell carcinoma Caki-1 cells. The anti-proliferative activity of EESB was associated with apoptosis induction, which was associated with the up-regulation of death receptor 4, the Fas ligand, and Bax and the down-regulation of Bid, XIAP, and cIAP-1 proteins. EESB treatment also induced mitochondrial dysfunction, proteolytic activation of caspase-3, -8, and -9 and degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase, ${\beta}$-catenin, and phospholipase C-${\gamma}1$. However, pretreatment of a pan-caspase inhibitor, z-VAD-fmk, significantly attenuated the EESB-induced apoptosis. Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent. Further studies will be needed to identify the active compounds that confer the anticancer activity of S. baicalensis.

• Clinical and Experimental Pediatrics
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• v.49 no.2
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• pp.198-202
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• 2006

Purpose : Fas is a cell surface receptor that transduces apoptotic death signals. Interaction of extracelluar domain of Fas with Fas ligand(FasL) triggers the apoptotic process in many diseases. We investigated the expression of Fas and FasL in the hippocampus of 7-day-old newborn rat brains following hypoxia-ischemia injury. Methods : The 7-days-old newborn rats were exposed to 8 percent oxygen for two hours after the ligation of right common carotid arteries. The newborn rats were killed and their brains were removed at 12, 14 and 48 hours after hypoxic-ischemic injury. The expressions of Fas and FasL of the right hippocampus were observed by western blotting and immunofluorescent staining. Results : Fas and FasL were strongly expressed in the right hippocampus ipsilateral to the ligation of the common carotid artery by western blotting at 12 hours following hypoxic-ischemic injury, and then slowly decreased. The immunofluorescent expressions of Fas and FasL strongly increased in the CA1 area of the right hippocampus at 12 and 24 hours following hypoxic-ischemic injury. The immunofluorescent expression of Fas decreased at 48 hours, but the expression of FasL persisted strongly at 48 hours following hypoxic-ischemic injury. Conclusion : The interaction of Fas with FasL on the cell surface may be involved in neuronal injury following hypoxic-ischemic injury in the developing brain.

• Microbiology and Biotechnology Letters
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• v.45 no.1
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• pp.27-34
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• 2017

$C/EBP{\beta}$ and $C/EBP{\delta}$ are required for the initiation of adipogenesis and induce the expression of key adipogenic regulators, such as $PPAR{\gamma}$ and $C/EBP{\alpha}$. In the present study, we have examined the effects of silibinin and its possible molecular mechanisms in regulating adipocyte differentiation and expression of $C/EBP{\beta}$ and $C/EBP{\delta}$ in the early stage of adipogenesis. Silibinin statistically significantly inhibits intracellular lipid accumulation and the mRNA expression of various genes involved at different stages during adipogenesis. Silibinin also suppresses expression of lipoprotein lipase (LPL), fatty acid binding protein 4 (AP2), and adiponectin in 3T3-L1 adipocytes. Thus, the anti-adipogenic effect of silibinin seems to originate from the ability to inhibit the expression of $C/EBP{\beta}$ and $C/EBP{\delta}$. Furthermore, silibinin decreases cell viability for differentiation period and induces apoptotic cell death through capspase-3 activation.

• Molecules and Cells
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• v.37 no.11
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• pp.785-794
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• 2014

Mitophagy, a cellular process that selectively targets dysfunctional mitochondria for degradation, is currently a hot topic in research into the pathogenesis and treatment of many human diseases. Considering that hypoxia causes mitochondrial dysfunction, which results in cell death, we speculated that selective activation of mitophagy might promote cell survival under hypoxic conditions. In the present study, we introduced the Regulator of calcineurin 1-1L (Rcan1-1L) to initiate the mitophagy pathway and aimed to evaluate the effect of Rcan1-1L-induced mitophagy on cell survival under hypoxic conditions. Recombinant adenovirus vectors carrying Rcan1-1L were transfected into human umbilical vein endothelial cells and human adult cardiac myocytes. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and Trypan blue exclusion assay, Rcan1-1L overexpression was found to markedly reverse cell growth inhibition induced by hypoxia. Additionally, Rcan1-1L overexpression inhibited cell apoptosis under hypoxic conditions, as detected by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis assay. Meanwhile, the mitochondria-mediated cell apoptotic pathway was inhibited by Rcan1-1L. In contrast, knockdown of Rcan1-1L accelerated hypoxia-induced cell apoptosis. Moreover, Rcan1-1L overexpression significantly reduced mitochondrial mass, decreased depolarized mitochondria, and downregulated ATP and reactive oxygen species production. We further delineated that the loss of mitochondrial mass was due to the activation of mitophagy induced by Rcan1-1L. Rcan1-1L overexpression activated autophagy flux and promoted translocation of the specific mitophagy receptor Parkin into mitochondria from the cytosol, whereas inhibition of autophagy flux resulted in the accumulation of Parkin-loaded mitochondria. Finally, we demonstrated that mitochondrial 1permeability transition pore opening was significantly increased by Rcan1-1L overexpression, which suggested that Rcan1-1L might evoke mitophagy through regulating mitochondrial permeability transition pores. Taken together, we provide evidence that Rcan1-1L overexpression induces mitophagy, which in turn contributes to cell survival under hypoxic conditions, revealing for the first time that Rcan1-1L-induced mitophagy may be used for cardioprotection.

• Journal of Life Science
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• v.31 no.10
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• pp.873-884
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• 2021

The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.151-159
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• 2019

Pruritus (itching) is classically defined as an unpleasant cutaneous sensation that leads to scratching behavior. Although the scientific criteria of classification for pruritic diseases are not clear, it can be divided as acute or chronic by duration of symptoms. In this study, we investigated whether skin injury caused by chemical (contact hypersensitivity, CHS) or physical (skin-scratching stimulation, SSS) stimuli causes initial pruritus and analyzed gene expression profiles systemically to determine how changes in skin gene expression in the affected area are related to itching. In both CHS and SSS, we ranked the Gene Ontology Biological Process terms that are generally associated with changes. The factors associated with upregulation were keratinization, inflammatory response and neutrophil chemotaxis. The Kyoto Encyclopedia of Genes and Genomes pathway shows the difference of immune system, cell growth and death, signaling molecules and interactions, and signal transduction pathways. Il1a, Il1b and Il22 were upregulated in the CHS, and Tnf, Tnfrsf1b, Il1b, Il1r1 and Il6 were upregulated in the SSS. Trpc1 channel genes were observed in representative itching-related candidate genes. By comparing and analyzing RNA-sequencing data obtained from the skin tissue of each animal model in these characteristic stages, it is possible to find useful diagnostic markers for the treatment of itching, to diagnose itching causes and to apply customized treatment.

• Nutrition Research and Practice
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• v.12 no.6
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• pp.494-502
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• 2018

BACKGROUND/OBJECTIVES: Reducing the number of adipocytes by inducing apoptosis of mature adipocytes as well as suppressing differentiation of preadipocytes plays an important role in preventing obesity. This study examines the anti-adipogenic and pro-apoptotic effect of red pepper seed water extract (RPS) prepared at $4^{\circ}C$ (RPS4) in 3T3-L1 cells. MATERIALS/METHODS: Effect of RPS4 or its fractions on lipid accumulation was determined in 3T3-L1 cells using oil red O (ORO) staining. The expressions of AMP-activated protein kinase (AMPK) and adipogenic associated proteins [peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR-{\gamma}$), CCAAT/enhancer-binding proteins ${\alpha}$ (C/EBP ${\alpha}$), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)] were measured in 3T3-L1 cells treated with RPS4. Apoptosis and the expression of Akt and Bcl-2 family proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), Bcl-2 like protein 4 (Bax), Bal-2 homologous antagonist/killer (Bak)] were measured in mature 3T3-L1 cells treated with RPS4. RESULTS: Treatment of RPS4 ($0-75{\mu}g/mL$) or its fractions ($0-50{\mu}g/mL$) for 24 h did not have an apparent cytotoxicity on pre and mature 3T3-L1 cells. RPS4 significantly suppressed differentiation and cellular lipid accumulation by increasing the phosphorylation of AMPK and reducing the expression of $PPAR-{\gamma}$, C/EBP ${\alpha}$, SREBP-1c, FAS, and ACC. In addition, all fractions except ethyl acetate fraction significantly suppressed cellular lipid accumulation. RPS4 induced the apoptosis of mature adipocytes by hypophosphorylating Akt, increasing the expression of the pro-apoptotic proteins, Bak, Bax, and Bad, and reducing the expression of the anti-apoptotic proteins, Bcl-2 and p-Bad. CONCLUSIONS: These finding suggest that RPS4 can reduce the numbers as well as the size of adipocytes and might useful for preventing and treating obesity.

• Journal of Life Science
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• v.31 no.2
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• pp.237-247
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• 2021

Immune responses in the central nervous system (CNS) function as the host's defense system against pathogens and usually help with repair and regeneration. However, chronic and exaggerated neuroinflammation is detrimental and may create neuronal damage in many cases. The NOD-, LRR-, and pyrin domain―containing 3 (NLRP3) inflammasome, a kind of NOD-like receptor, is a cytosolic multiprotein complex that consists of sensors (NLRP3), adaptors (apoptosis-associated speck like protein containing a caspase recruitment domain, ASC) and effectors (caspase 1). It can detect a broad range of microbial pathogens along with foreign and host-derived danger signals, resulting in the assembly and activation of the NLRP3 inflammasome. Upon activation, NLRP3 inflammasome leads to caspase 1-dependent secretion of the pro-inflammatory cytokines IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. NLRP3 inflammasome is highly expressed in CNS-resident cell types, including microglia and astrocytes, and growing evidence suggests that NLRP3 inflammasome is a crucial player in the pathophysiology of several neuroinflammatory and psychiatric diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, traumatic brain injury, amyotrophic lateral sclerosis, and major depressive disorder. Thus, this review describes the molecular mechanisms of NLRP3 inflammasome activation and its crucial roles in the pathogenesis of neurological disorders.