• Molecules and Cells
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• v.38 no.4
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• pp.356-361
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• 2015

Mitochondrial dysfunction is associated with insulin resistance and diabetes. We previously showed that retinoid X receptor ${\alpha}$ ($RXR{\alpha}$) played an important role in transcriptional regulation of oxidative phosphorylation (OXPHOS) genes in cells with mitochondrial dysfunction caused by mitochondrial DNA mutation. In this study, we investigated whether mitochondrial dysfunction induced by incubation with OXPHOS inhibitors affects insulin receptor substrate 1 (IRS1) mRNA and protein levels and whether $RXR{\alpha}$ activation or overexpression can restore IRS1 expression. Both IRS1 and $RXR{\alpha}$ protein levels were significantly reduced when C2C12 myotubes were treated with the OXPHOS complex inhibitors, rotenone and antimycin A. The addition of $RXR{\alpha}$ agonists, 9-cis retinoic acid (9cRA) and LG1506, increased IRS1 transcription and protein levels and restored mitochondrial function, which ultimately improved insulin signaling. $RXR{\alpha}$ overexpression also increased IRS1 transcription and mitochondrial function. Because $RXR{\alpha}$ overexpression, knock-down, or activation by LG1506 regulated IRS1 transcription mostly independently of mitochondrial function, it is likely that $RXR{\alpha}$ directly regulates IRS1 transcription. Consistent with the hypothesis, we showed that $RXR{\alpha}$ bound to the IRS1 promoter as a heterodimer with peroxisome proliferator-activated receptor ${\delta}$ ($PPAR{\delta}$). These results suggest that $RXR{\alpha}$ overexpression or activation alleviates insulin resistance by increasing IRS1 expression.

• Microbiology and Biotechnology Letters
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• v.51 no.3
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• pp.280-288
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• 2023

In strawberry farming, most parts of strawberry stems but the fruit have been dumped. Therefore, this study attempted to investigate the antioxidant and anti-inflammatory effects of strawberry stems which are thrown away after farming. For this, strawberry stem extracts were obtained, using hot water and 70% ethanol. First, total polyphenol contents of the hot water and ethanol extract were checked (265.4 ± 0.12 mg TAE/100 g, 503.88 ± 0.2 mg TAE/100 g). For analysis of antioxidant activities, electron donating ability (EDA) and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity were measured. Both extracts increased in a dose-dependent fashion, and similar effects with vitamin C (control group) were confirmed. In terms of cell viability of the hot water and ethanol extracts of strawberry stems, 'RAW 264.7' was 99% or higher at 500 ㎍/ml. In addition, cell experiments were conducted at 50, 100 and 500 ㎍/ml where cell viability is above 99%. In terms of inhibition of the inflammatory mediator 'nitric oxide (NO)', the hot water and ethanol extracts of strawberry stems were 37.9% and 38.8% respectively, confirming the inhibition of NO production. To check anti-inflammatory activities, protein and mRNA expressions of 'iNOS' and 'COX-2' were measured, using RAW 264.7. Compared to the LPS group, the protein expression of the inflammatory mediators was inhibited in the hot water and ethanol extract-treated groups. The above results confirmed that the hot water and ethanol extracts of strawberry stems are valuable as natural substances with antioxidant and anti-inflammatory activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.529-541
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• 2003

Yukmijihwang-tang has been widely used as an and-aging herbal medicine for hundred years in Asian countries. Numerous studies show that Yukmijihwangtang has anti-oxidative effect both in vivo and in vitro. It has been reported that Moutan Cortex Radicis extract (MCR) was the most effective herb in Yukmijihwang-tang on undifferentiated PC12 cells upon oxidative-stressed with hydrogen peroxide. The purpose of this study is to; 1) evaluate the recovery of neuronal damage by assessing the anti-oxidant effect of MCR on PC12 cells differentiated with nerve growth factor (NGF), 2) identify candidate genes responsible for anti-oxidative effect on differentiated PC12 cells by oligonucleotide chip microarray. PC12 cells, which were differentiated by treating with NGF, were treated without or with hydrogen peroxide in the presence or absence of various concentration of MCR. Cell survival was determined by using MTS assay. Measurement of intracellular reactive oxygen species (ROS) generation was determined using the H2DCFDA assay The viability of cells treated with MCR was significantly recovered from stressed PC12 cell. In addition, wide rage of concentrations of MCR shows dose-dependent inhibitory effect on ROS production in oxidative-stressed cells. Total RNAs of cells without treatment(Control group), only treated with H₂O₂ (stressed group) and treated with both H₂O₂ and of MCR (MCR group) were isolated, and cDNAs was synthesized using oligoT7(dT) primer. The fragmented cRNAs, synthesized from cDNAs, were applied to Affymetrix GeneChip Rat Neurobiology U34 Array. mRNA of Calcium/calmodulin-dependent protein kinase II delta subunit(CaMKII), neuron glucose transporter (GLUT3) and myelin/oligodendrocyte glycoprotein(MOG) were downregulated in Stressed group comparing to Control group. P2X2-5 receptor (P2X2R-5), P2X2-4 receptor (P2X2R-4), c-fos, 25 kDa synaptosomal attachment protein(SNAP-25a) and GLUT3 were downregulated, whereas A2 adenosine receptor (A2AR), cathechol-O-methyltransferase(COMT), glucose transporter 1 (GLUT1), EST223333, heme oxygenase (HO), VGF, UI-R-CO-ja-a-07-0-Ul.s1 and macrophage migration inhibitory factor (MIF) were upregulated in MCA group comparing to Control group. Expression of Putative potassium channel subunit protein (ACK4), P2X2A-5, P2X2A-4, Interferon-gamma inducing factor isoform alpha precursor (IL-18α), EST199031, P2XR, P2X2 purinoceptor isoform e (P2X2R-e), Precursor interleukin 18 (IL-18) were downregulated, whereas MOO, EST223333, GLUT-1, MIF, Neuronatin alpha, UI-R-C0-ja-a-07-0-Ul.s1, A2. adenosine receptor, COMT, neuron-specific enolase (NSE), HO, VGF, A rat novel protein which is expressed with nerve injury (E12625) were upregulated in MCR group comparing to Stressed group. The results suggest that decreased viability and AOS production of PC12 cell by H₂O₂ may be, at lease, mediated by impaired glucose transporter expression. It is implicated that the MCR treatment protect PC12 cell from oxidative stress via following mechanisms; improving glucose transport into the cell, enhancing expression of anti-oxidative genes and protecting from dopamine cytotoxicity by increment of COMT and MIF expression. The list of differentially expressed genes may implicate further insight on the action and mechanism behind the anti-oxidative effects of herbal extract Moutan Cortex Radicis.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.4
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• pp.595-606
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• 2018

Objective: The Fusarium mycotoxins of deoxynivalenol (DON) and zerolenone (ZEN) cause health hazards for both humans and farm animals. Therefore, the main intention of this study was to reveal DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the liver of piglets. Methods: In the present study, 15 six-week-old piglets were randomly assigned to the following three different dietary treatments for 4 weeks: control diet, diet containing 8 mg DON/kg feed, and diet containing 0.8 mg ZEN/kg feed. After 4 weeks, liver samples were collected and sequenced using RNA-Seq to investigate the effects of the mycotoxins on genes and gene networks associated with the immune systems of the piglets. Results: Our analysis identified a total of 249 differentially expressed genes (DEGs), which included 99 upregulated and 150 downregulated genes in both the DON and ZEN dietary treatment groups. After biological pathway analysis, the DEGs were determined to be significantly enriched in gene ontology terms associated with many biological pathways, including immune response and cellular and metabolic processes. Consistent with inflammatory stimulation due to the mycotoxin-contaminated diet, the following Kyoto encyclopedia of genes and genomes pathways, which were related to disease and immune responses, were found to be enriched in the DEGs: allograft rejection pathway, cell adhesion molecules, graft-versus-host disease, autoimmune thyroid disease (AITD), type I diabetes mellitus, human T-cell leukemia lymphoma virus infection, and viral carcinogenesis. Genome-wide expression analysis revealed that DON and ZEN treatments downregulated the expression of the majority of the DEGs that were associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9), proliferation (insulin-like growth factor 1, major facilitator superfamily domain containing 2A, insulin-like growth factor binding protein 2, lipase G, and salt inducible kinase 1), and other immune response networks (paired immunoglobulin-like type 2 receptor beta, Src-like-adaptor-1 [SLA1], SLA3, SLA5, SLA7, claudin 4, nicotinamide N-methyltransferase, thyrotropin-releasing hormone degrading enzyme, ubiquitin D, histone $H_2B$ type 1, and serum amyloid A). Conclusion: In summary, our results demonstrated that high concentrations DON and ZEN disrupt immune-related processes in the liver.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.1
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• pp.138-148
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• 2018

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.

• Journal of Microbiology
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• v.45 no.6
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• pp.510-514
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• 2007

Twenty-five bacterial strains that secrete mucous materials were isolated from sediment obtained from King George Island, Antarctica. Seven of these strains proved capable of producing cryoprotective exopolysaccharides. The strain KOPRI 21653 was selected for the further study of an anti-ice-nucleating polysaccharide (ANP), which originated from a polar region. KOPRI 21653 was identified as Pseudoalteromonas arctica as the result of 16S rRNA analysis. The exopolysaccharide, P-21653, was purified completely from the KOPRI 21653 cell culture via column chromatography and protease treatment. The principal sugar components of P-21653 were determined to be galactose and glucose, at a ratio of 1:1.5, via GC-MS analysis. The cryoprotective activity of P-21653 was characterized via an E. coli viability test. In the presence of 0.1% (w/v) P-21653, the survival ratio of E. coli cells was as high as 82.6% over three repeated freeze-thaw cycles. The survival ratio decreased drastically to 71.5 and 48.1 %, respectively, in five and seven repeated cycle conditions; however, the survival ratios were greater over three (96.6-92.1%) to seven (100.5-91.6%) freeze-thaw cycles in the presence of 0.5 and 1.0% (w/v) P-21653. In addition, at much lower concentrations (0.1-1.0%), P-21653 resulted in survival ratios (83.1-98.4%) similar to those of two commercially available cryoprotectants ($V_{EG}$ plus X-1000, 92.9% and $V_{M3}$, 95.3%), which were utilized at the recommended concentrations (90%). The biochemical characteristics of exopolysaccharide P-21653 reflect that this compound may be developed as a useful cryoprotectant for use in medical applications and in the food industry.

• Toxicological Research
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• v.14 no.2
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• pp.123-127
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• 1998

BRCA1 is a tumor suppresser gene in familial cases of breast cancer. It has been controversial whether the subcellular localization of BRCA1 is located in nuclei or cytoplasm in normal human breast cells. We found that a p220 protein was expressed in Type II Normal human breast epithelial cells (NHBEC) but not in Type I NHBEC in Western blot analysis using the 17F8 (3A2) antibody. Immunostaining using the same antibody revealed positive staining in nuclei, cytoplasm and perinuclei of Type II cells and negative staining in Type I NHBEC. The p220 protein, however, was expressed in SV40 immortalized Type I NHBEC and tumorigenic cells derived from them after x-ray and neu oncogene treatment. The subcelluar localization was mostly cytoplasmic and punctate in the nuclei. The breast carcinoma cell lines, MCF-7 and T47D, also expressed the p220 protein. Using RT-PCR, we observed the expression of BRCA1 mRNA in both Type I and Type II NHBEC. This result indicated that there might be mechanisms involved in post-translational or translational regulation of BRCA1 gene. It is speculated that the absence of BRCA1 protein expression in Type I NHBEC might playa role in their susceptibility to neoplastic transformation.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.11
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• pp.1598-1608
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• 2013

An optimum dietary carbohydrate content is important for maximum fish growth. In this study, we fed Wuchang bream (Megalobrama amblycephala) with either control diet (30.42%) or high carbohydrate diet (52.92%) for 90 d. Fish were fed to apparent satiation three times daily in an aquarium with automatic temperature control and circulated water. Growth performance, plasma biochemical parameters, hepatic morphology and enzyme activities were determined. It was shown that compared to fish fed control diet, fish fed high carbohydrate diet had higher plasma triglyceride and cortisol levels for d 90, and lower alkaline phosphatase level for d 45, lower hepatic superoxide dismutase and total antioxidative capacity for d 90, higher malondialdehyde for d 45 and glycogen content for d 45 and 90 (p<0.05). Histological and transmission electron microscopy studies showed that hepatocytes of fish fed high carbohydrate diet contained large lipid droplets, causing displacement of cellular organelles to periphery of hepatocytes. The relative level of hepatic heat shock protein 70 (HSP70) mRNA of Wuchang bream fed high carbohydrate diet was significantly higher than that of fish fed the control diet for 90 d (p<0.05). These changes led to decreased specific growth rate and increased feed conversion ratio (p<0.05). Upon hypoxia challenge, fish fed high carbohydrate diet had higher cumulative mortality than those fed the control diet (p<0.05). These results suggested that high dietary carbohydrate (52.92%) was detrimental to the growth performance and health of Wuchang bream.

• Journal of Life Science
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• v.22 no.6
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• pp.815-822
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• 2012

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), a natural stilbene, is an analogue of resveratrol. Although recent experimental data have revealed the health benefit potency of piceatannol, the molecular mechanisms underlying the anti-cancer activity have not yet been studied in detail. In the present study, the further possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human lung cancer A549 cells were investigated. Exposure of A549 cells to piceatannol resulted in growth inhibition and induction of apoptosis. Apoptosis induction of A549 cells by piceatannol showed correlation with proteolytic activation of caspase-3, -8, and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase, phospholipase C-${\gamma}1$, ${\beta}$-catenin, and Inhibitor caspase-activated DNase. The increase in apoptosis by piceatannol treatment was also associated with an increase of pro-apoptotic Bax expression and decrease of anti-apoptotic Bcl-2 and Bcl-xL expression, and caused down-regulation of the inhibitor of apoptosis protein family members and up-regulation of Fas and Fas legend. In addition, piceatannol treatment markedly inhibited the expression of mRNA and proteins of inducible nitric oxide (NO) synthase, and the levels of NO production were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. The results indicate that piceatannol may have therapeutic potential against human gastric cancer cells.

• The Korean Journal of Mycology
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• v.39 no.1
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• pp.31-38
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• 2011

In this study, 81 commercial strains of Pleurotus species cultivated in South Korea were analyzed with randomly amplified polymorphic DNA (RAPD) technique. Sequence characterized amplified region (SCAR) markers were developed by designing from one RAPD polymorhic band specific to Suhan strain. The SCAR primer pair 'S-OPA13-1' amplified a 590-bp fragment in the varieties originated from Suhan strain. The Blast search of S-OPA13-1 showed high homology to the POMFBO1 P. ostreatus cDNA clone MFB02-A05 and Laccaria bicolor S238N-H82. The results showed that this SCAR marker can clearly distinguish Suhan strains from Pleurotus spp.