• Korean Journal of Veterinary Service
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• v.44 no.4
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• pp.195-207
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• 2021

Species A rotaviruses (RVAs) replicate and assemble their immature particles within electron dense compartments known as viroplasms, where lipid droplets (LDs) interact with the viroplasm and facilitate viral replication. Despite the importance of LD formation in the life cycle of RVAs, the upstream molecules modulating LD formation remain unclear. This study aimed to find out the role of sterol regulatory element-binding proteins (SREBPs) in reprogramming of LD formation after RVA infection. Here, we demonstrate that RVA infection reprograms the sterol regulatory element-binding proteins (SREBPs)-dependent lipogenic pathways in virus-infected cells, and that both SREBP-1 and -2 transactivated genes, which are involved in fatty acid and cholesterol biosynthesis, are essential for LD formation. Our results showed that pharmacological inhibition of SREBPs using AM580 and betulin and inhibition of their downstream cholesterol biosynthesis (simvastatin for HMG-CoA reductase) and fatty acid enzymes (TOFA) negatively modulated the intracellular triacylglycerides and cholesterol levels and their resulting LD and viroplasm formations. Interestingly, pharmacological inhibition of SREBPs significantly reduced RVA protein synthesis, genome replication and progeny production. This study identified SREBPs-mediated lipogenic reprogramming in RVA-infected host cells, which facilitates virus replication through LD formation and its interaction with viroplasms, suggesting that SREBPs can be a potential target for the development of efficient and affordable therapeutics against RVA infection.

• Journal of Life Science
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• v.28 no.10
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• pp.1233-1243
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• 2018

Sterol regulatory-element binding proteins (SREBPs) are a family of transcription factors that regulate lipid homeostasis and metabolism by controlling the expression of enzymes required for endogenous cholesterol, fatty acid (FA), triacylglycerol, and phospholipid synthesis. The three SREBPs are encoded by two different genes. The SREBP1 gene gives rise to SREBP-1a and SREBP-1c, which are derived from utilization of alternate promoters that yield transcripts in which distinct first exons are spliced to a common second exon. SREBP-2 is derived from a separate gene. Additionally, SREBPs are implicated in numerous pathogenic processes, such as endoplasmic reticulum stress, inflammation, autophagy, and apoptosis. They also contribute to obesity, dyslipidemia, diabetes mellitus, and nonalcoholic fatty liver diseases. Genome-wide analyses have revealed that these versatile transcription factors act as important nodes of biological signaling networks. Changes in cell metabolism and growth are reciprocally linked through SREBPs. Anabolic and growth signaling pathways branch off and connect to multiple steps of SREBP activation and form complex regulatory networks. SREBPs are activated through the PI3K-Akt-mTOR pathway in these processes, but the molecular mechanism remains to be understood. This review aims to provide a comprehensive understanding of the role of SREBPs in physiology and pathophysiology at the cell, organ, and organism levels.

• The Korean Journal of Applied Statistics
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• v.29 no.7
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• pp.1247-1255
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• 2016

Kim and Lee (2015) identified a superior FABP4 gene that improves the grade and fatty acid of Korean cattle. This study selects a superior genotype by expanding genes that influence the economic traits of Korean cattle. Expanded genes are FABP4, SCD, FASN and SREBPs that are related to grade and fatty acid (Oh, 2014). We use the adjusted economic-trait values with environmental factors excluded. We also applied multifactor dimensionality reduction(MDR) method to data of the adjusted economic-trait values. As a result, we identified superior genes and genotypes which improved the grade and fatty acid of Korean cattle.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.989-995
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• 2010

The aim of this study was to investigate the effect of Taeeumjowuitanggagam-bang(TJV) on the mRNA expression of adipocytokines (TNF-${\alpha}$ and IL-6), and SREBPs. Mice were divided into 4 groups ; a normal group of db/+ mice, a control group of db/db mice, a group (db/db mice) treated with TJV 200 mg/kg, and a group (db/db mouse) treated with TJV 500 mg/kg. They were treated orally with TJV and measured their body weight every other day during 9 weeks. After that, we measured the mRNA expression of adipocytokines (TNF-${\alpha}$ and IL-6) and SREBPs (SREBE-1a and SREBP-1c) in liver, and blood concentration of total cholesterol, triglyceride, too. In addition, liver samples were fixed in 4% PFA for 2 hours and stored in $-70^{\circ}C$. Liver tissues were embedded in Optical cutting temperature(OCT) compound and 30 ${\mu}m$ sections were cut. Tissue sections were stained Oil-Red-O to visualize neutral lipids. Nuclei were stained with hematoxylin solution. In result, the TJV reduced the mRNA expressions of TNF-${\alpha}$ and IL-6 and SREBPs in liver and stained liver tissue less red than control group. However, there was no significant differences in total cholestreol and triglyceride blood concentration and body weight among groups. The TJV has inhibitory effect on the mRNA expression of adipocytokines and SREBPs. Therefore, it is assumed that the TJV is related to inhibiting lipogenesis in the liver

• Journal of the Korean Data and Information Science Society
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• v.26 no.3
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• pp.677-685
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• 2015

Disease of human and economic traits of livestocks are affected a lot by gene combination effect rather than a single gene effect. In this study, we used SNPHarvester method that supplement existing method in order to investigate the interaction of these genes. The used genes are SREBPs (g.3270+10274 C>T, g.13544 T>C) and FABP4 (g.2634+1018 A>T, g.2988 A>G, g.3690 G>A, g.3710 G>C, g.3977-325 T>C, g.4221 A>G) that are closely related to the fatty acid composition affecting the meatiness of Korean cattle. The economic traits which are used are oleic acid (C18:1), monounsaturated fatty acid (MUFA), marbling score (MS). First, we have utilized the SNPHarvester method in order to find excellent gene combination, and then used the multifactor dimensionality reduction method in order to identify excellent genotype in gene combination.

• 한국균학회소식:학술대회논문집
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• 2015.05a
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• pp.15-15
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• 2015

Aspergillus fumigatus is a major cause of invasive aspergillosis (IA), a significant health issue worldwide with high mortality rates up to 95%. Our lab is interested in how A. fumigatus adapts to low oxygen conditions 'hypoxia', which is one of the important host microenvironments. A. fumigatus SrbA is a basic helix-loop-helix (bHLH) transcriptional regulator and belongs to sterol regulatory element binding protein (SREBP) family members. Loss of SrbA completely blocks growth in hypoxia and results in avirulence in murine models of IA suggesting an essential role of SrbA in hypoxia adaptation and virulence in A. fumigatus. We conducted chromatin immunoprecipitation sequencing (ChIP-seq) with A. fumigatus wild type using a SrbA specific antibody, and 97 genes were revealed as SrbA direct targets. One of the 'SrbA regulons' (AFUB_099590) was a putative bHLH transcriptional regulator whose sequence contained a characteristic tyrosine substitution in the basic portion of the bHLH domain of SREBPs. Therefore, we designated AFUB_099590 SrbB. Further characterization of SrbB demonstrated that SrbB is important for radial growth, biomass production, and biosynthesis of heme intermediates in hypoxia and virulence in A. fumigatus. A series of quantitative real time PCR showed that transcription of several SrbA regulons is coordinately regulated by two SREBPs, SrbA and SrbB in hypoxia. This suggests that SrbA and SrbB have both dependent and independent functions in regulation of genes responsible for hypoxia adaptation in A. fumigatus. Together, our data provide new insights into complicated roles of SREBPs in adaptation of host environments and virulence in pathogenic fungi.

• Journal of Life Science
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• v.31 no.9
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• pp.796-805
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• 2021

Hepatic endoplasmic reticulum (ER) stress contributes to the development of steatosis and insulin resistance. The components of unfolded protein response (UPR) regulate lipid metabolism. Recent studies have reported an association between ER stress and aberrant cellular lipid control; moreover, research has confirmed the involvement of sterol regulatory element-binding proteins (SREBPs)-the central regulators of lipid metabolism-in the process. However, the exact role of SREBPs in controlling lipid metabolism during ER stress and its contribution to fatty liver disease remain unknown. Here, we show that SREBP-1c deficiency protects against ER stress-induced hepatic steatosis in mice by regulating UPR, inflammation, and fatty acid oxidation. SREBP-1c directly regulated inositol-requiring kinase 1α (IRE1α) expression and mediated ER stress-induced tumor necrosis factor-α activation, leading to a reduction in expression of peroxisome proliferator-activated receptor γ coactivator 1-α and subsequent impairment of fatty acid oxidation. However, the genetic ablation of SREBP-1c prevented these events, alleviating hepatic inflammation and steatosis. Although the mechanism by which SREBP-1c deficiency prevents ER stress-induced inflammatory signaling remains to be elucidated, alteration of the IRE1α signal in SREBP-1c-depleted Kupffer cells might be involved in the signaling. Overall, the results suggest that SREBP-1c plays a crucial role in the regulation of UPR and inflammation in ER stress-induced hepatic steatosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.638-645
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• 2010

The aim of this study was to investigate the effect of Taeeumjowuitanggagam-bang (TJV) on the mRNA expression of Sterol regulatory element binding proteins (SREBPs), Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and Interlukin-6 (IL-6) that are considered to play an important role in lipid and glucose metabolism. For diet-induced obese studies, we split mice into 2 groups. The low fat diet group (LFD, n=8) were supplied with general diet for 10 weeks and the high fat diet group (HFD, n=18) were supplied with 60 kcal% fat diet for 10 weeks. And then The HFD group, the diet-induced obese group, were divided into 3 groups ; a group supplied with normal saline, a group treated with TJV 200 mg/kg and a group treated with TJV 500 mg/kg. They were treated orally with TJV and measured their body weight every day during 10 weeks. After that, we measured mRNA expressions of TNF-$\alpha$, IL-6 and SREBP-1c in liver, and blood concentrations of glucose, total cholesterol and triglyceride too. The results are as follows. The TJV reduced glucose and total cholesterol of blood concentration. The TJV reduced the mRNA expressions of TNF-$\alpha$ and SREBPs in liver. However, We couldn't find the TJV effects on the mRNA expression of IL-6, triglyceride blood concentration, and body weight among groups. The TJV stained liver tissue less red than control group. These results suggest that TJV may be effective for regulation of lipid and glucose metabolism in liver.

• Journal of the Korean Data and Information Science Society
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• v.25 no.5
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• pp.1011-1024
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• 2014

This study is to identify the relationship between unsaturated fatty acids, which are indicators of beef flavor, and unsaturated fatty acid biosynthetic enzymes, which are associated with SNPs in the SCD, SREBPs, $PPAR{\gamma}$, FABP4, FASN and LPL in Hanwoo population. For analysis of fatty acid in Hanwoo, we used to Hanwoo steer(n=513). Also, following an analysis of the relationship raised from Gyeongbuk province region. FABP4; g.3977-325 T>C was selected and the distribution of beef grade of g.3977-325 T>C related in field trial was proved very excellent.

• Journal of the Korean Applied Science and Technology
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• v.31 no.1
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• pp.101-112
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• 2014

The aim of this study was to evaluate the biological mechanism of orally administered ethanolic extract of fly maggot(EM) on hypocholesterolemic rats fed a high-cholesterol diet. Sprague Dawley male rats were divided into four groups (EM dose control=0, 5.0, 7.0, and 9.0 mg/100 g BW) and were treated for 6 weeks. EM groups revealed a significant reduction in serum triglyceride, total cholesterol, and LDL-C when compared with the control group(p<0.05). HMG-CoA reductase activity in EM groups were lower than those of the control group, but total sterol, neutral sterol, and bile acid excretion were increased in EM groups when compared with the control group(p<0.05). To identify the biological mechanism of EM towards the hypocholesterolemic effect, sterol response element binding proteins (SREBPs) and the peroxisome proliferator-activated receptors ($PPAR{\alpha}$ transcription system were determined in rats fed a high-cholesterol diet. It was discovered that EM suppress the expression of SREBP-$1{\alpha}$ and SREBP-2 mRNA in the liver tissues of high-cholesterol diet fed rats, while simultaneously increasing the expression of $PPAR{\alpha}$ mRNA(p<0.05). This finding indicates that EM may have hypocholesterolemic effects in rats fed a high-cholesterol diet, by regulating cholesterol metabolism-related biochemical parameters and SREBP-$1{\alpha}$ SREPB-2 and $PPAR{\alpha}$gene expression.