• KSBB Journal
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• v.18 no.4
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• pp.329-334
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• 2003

The present study was aimed at investigating the regulatory mechanism in tissue-specific expression of insulin-like growth factor-I (IGF-I) gene. The expression of IGF-I gene was determined by a solution hybridization/RNase protection assay using total RNA prepared from rat liver or brain of various ages. The levels of IGF-I transcripts were increased in liver gradually after birth, but decreased in brain. By using an oligonucleotide (FRE) corresponding to the C/EBP binding site of the rat IGF-I exon 1, multiple forms of C/EBP${\alpha}$ and C/EBP${\beta}$ proteins, which have DNA-binding activity, were detected in the rat liver or brain. Western immunoblot and southwestern analyses show that p42$\^$C/EBP${\alpha}$/, p38$\^$C/EBP${\alpha}$/, p35$\^$C/EBP${\alpha}$/, p38$\^$C/EBP${\beta}$/, and p35$\^$C/EBP${\beta}$ form specific complexes with the IGF-I exon 1 oligonucleotide in liver nuclear extract and that p42$\^$C/EBP${\alpha}$/ and p38$\^$C/EBP${\beta}$/ form complexes in brain. These data suggest that the formation of FRE-C/EBP isoform complexes may play important roles in the tissue-specific regulation of IGF-I gene expression.

• BMB Reports
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• v.52 no.6
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• pp.391-396
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• 2019

Receptor activator of nuclear factor kappa B ligand (RANKL) expression in osteoblasts is regulated by 1,25-dihydroxyvitamin D3 (1,25D3). CCAAT/enhancer-binding protein beta ($C/EBP{\beta}$) has been proposed to function as a transcription factor and upregulate RANKL expression, but it is still uncertain how $C/EBP{\beta}$ is involved in 1,25D3-induced RANKL expression of osteoblasts. 1,25D3 stimulation increased the expression of RANKL and $C/EBP{\beta}$ genes in osteoblasts and enhanced phosphorylation and stability of these proteins. Moreover, induction of RANKL expression by 1,25D3 in osteoblasts was downregulated upon knockdown of $C/EBP{\beta}$. In contrast, $C/EBP{\beta}$ overexpression directly upregulated RANKL promoter activity and exhibited a synergistic effect on 1,25D3-induced RANKL expression. In particular, 1,25D3 treatment of osteoblasts increased $C/EBP{\beta}$ protein binding to the RANKL promoter. In conclusion, $C/EBP{\beta}$ is required for induction of RANKL by 1,25D3.

• Proceedings of the Korean Environmental Health Society Conference
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• 2005.06a
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• pp.341-344
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• 2005

The expression of the glutathione S-transferase (GST), whose induction accounts for antioxidant defense system, is regulated by activation of CCAAT/enhancer binding protein ${\beta}$ ($C/EBP{\beta}$), Sick house syndrome (SHS) presents healthy damage owing to the indoor environment of a building. Toluene has been implicated in one of the important causes of SHS. The present study investigated the effects of toluene treatment on the induction of GSTA2 gene and its mechanism. H411E cells treated with toluene, and GSTA2 expression was determined by immunoblot analysis. The translocation of $C/EBP{\beta}$ was assessed by immunocytochemical assays. $C/EBP{\beta}$ DNA binding activity was determined by electrophoretic mobility shift assays. The role of the C/EBP binding site in the induction of the GSTA2 gene was assessed by luciferase reporter-gene activity. Toluene induced GSTA2 protein expression. In toluene-treated cells, $C/EBP{\beta}$ translocated to the nucleus and bound to the consensus sequence of C/EBP (TTGCGCAA). Toluene treatment increased luciferase reporter-gene activity in cells transfected with the C/EBP-containing regulatory region of the GSTA2 gene. Oxidative stress is believed to play an important role in the induction of GSTA2 gene by toluene This study shows that toluene-induced GSTA2 gene expression is dependent upon nuclear translocation and binding of $C/EBP{\beta}$ to the C/EBP response element in the GSTA2 gene promoter.

• 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.

• Biomedical Science Letters
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• v.14 no.3
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• pp.131-137
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• 2008

Adipogenesis is a complex sequence of events that culminates in the differentiation of fibroblast-like preadipocytes into specialized lipid-filled adipocytes and also involves a cascade of expression of many transcription factors such as peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$ and CCAAT/enhancer-binding proteins (C/EBPs). $PPAR{\gamma}$ and C/EBPs transcriptionally transactivate adipocyte specific genes, including fatty acid transport protein (FAT/CD36) and leptin. To determine whether $17{\beta}$-estradiol modulates $C/EBP{\alpha}$ actions on adipogenesis in high fat diet-fed female ovariectomized (OVX) C57BL/6 mice, mice were treated with $17{\beta}$-estradiol for 7 days and the effects of $17{\beta}$-estradiol on adipose tissue mass and expression of adipocyte specific gene as well as $C/EBP{\alpha}$ were measured. Compared to vehicle-treated OVX control mice, OVX mice treated with $17{\beta}$-estradiol for 7 days had lower adipose tissue weights that were similar to weights in high fat diet-fed sham-operated (Sham) mice. OVX mice showed the increased expression of $C/EBP{\alpha}$ mRNA compared with Sham mice. However, $17{\beta}$-estradiol treatment in OVX mice inhibited OVX induced-$C/EBP{\alpha}$ activation, indicating that $17{\beta}$-estradiol may act as an inhibitor of $C/EBP{\alpha}$ action. Moreover, $17{\beta}$-estradiol decreased mRNA levels of adipocyte marker genes, such as lipoprotein lipase, FAT/CD36 and leptin, to levels in Sham mice. These results suggest that down-regulation of adipogenesis by $17{\beta}$-estradiol may be due to reduced adipose $C/EBP{\alpha}$ activities in female OVX C57BL/6 mice.

• Journal of Life Science
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• v.19 no.11
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• pp.1637-1643
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• 2009

Shikonin, a component of Lithospermum erythrorhizon Sieb. et Zucc, exerts various characteristics such as anti-inflammatory, anti-cancer and anti-obesity functions. To elucidate the molecular mechanism of shikonin-induced inhibition of adipogenesis, we analyzed the mRNA expression level of various adipogenesis-related factors including C/EBPs (CCAAT/enhancerbinding proteins) and $PPAR{\gamma}$ (peroxisome proliferator-activated receptor $\gamma$). The data showed that mRNA expressions of C/$EBP{\beta}$ and C/$EPB{\delta}$ were only slightly changed by shikonin treatment, but mRNA expressions of $PPAR{\gamma}$ and C/$EPB{\alpha}$ were significantly down-regulated. Then, we tested whether upstream regulators of C/$EBP{\beta}$ and $PPAR{\gamma}$ were involved in anti-adipogenesis of shikonin. C/$EBP{\gamma}$ and CHOP (C/EBP homologous protein), which are upstream regulators of C/$EBP{\beta}$, were not affected by shikonin treatment. On the contrary, the mRNA level of KROX20 was markedly down-regulated by shikonin treatment. These results suggest that KROX20 might regulate downstream factors of adipogenesis through C/$EBP{\beta}$-independent pathway. The expression of KLF15 (Kruppel-like factor15), which is a member of KLF family and is a upstream regulator of $PPAR{\gamma}$, was dramatically decreased by shikonin treatment, but KLF2 was not changed. Shikonin had no impact on the expression of KLF5 in the early stage of adipogenesis, but shikonin increased expression of KLF5 in the late stage of adipogenesis. Even though mRNA expression of KLF5 was moderately changed by shikonin treatment, its effect may be small compared with the effect of KLF15, which was markedly inhibited. Taken together, these results suggest that shikonin inhibits adipogenesis through the down-regulation of $PPAR{\gamma}$ and C/$EPB{\alpha}$, which is mediated by the down-regulation of two pro-adipogenic factors, KROX20 and KLF15.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.144-144
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• 2002

• Korean Journal of Food Science and Technology
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• v.47 no.2
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• pp.246-253
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• 2015

In this study, we evaluated the lipoprotein lipase (LPL) inhibitory activity of 11 water extracts derived from Cinnamomum cassia Blume, Sarcodon aspratus, Cordyceps militaris, Crataegus pinnatifida Bunge, Corni fructus, Allium cepa, Coix lacryma-jobi, Plantago asiatica L., Lentinus edodes, Rosa rugosa, and Foeniculum fructus. The results of the LPL secretion and activity assay showed Sarcodon aspratus (NE) extract have an LPL secretion inhibitory acitivity. The cause of reduction in LPL secretion after NE treatment was investigated using molecular biology methods. NE treatment affected the LPL content in cells, but did not affect LPL mRNA expression. It also increased the mRNA expression level of sortilin-related receptor LDLR class A (SorLA), a receptor that induces endocytosis and intracellular trafficking of LPL. Finally, cell fractionation revealed that NE treatment induced the expression of CCAAT-enhancer-binding protein beta ($C/EBP{\beta}$), a SorLA transcription factor, in the nuclei of 3T3-L1 adipocytes. These results show that NE's anti-obesity effect involves inhibition of LPL secretion through $C/EBP{\beta}$-mediated induction of SorLA expression.

• Journal of Life Science
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• v.22 no.10
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• pp.1399-1406
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• 2012

The present study was conducted to evaluate the effects of various extracts of Hizikia fusiforme on the anti-obesity effects in 3T3-L1 preadipocytes. We used H. fusiforme extracts from ethanol (EEHF), dichloromethane (CFHF), ethyl acetate (EAFHF), butanol (BFHF), and water (WFHF). Treatment with these extracts significantly suppressed terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner as confirmed by a decrease in lipid droplet content through Oil Red O staining; this effect was higher in WFHF than in other extracts. The concentrations of cellular triglyceride were also reduced in 3T3-L1 cells by exposure with these extracts, especially when compared with the controls. Treatment with 200 ${\mu}g/ml$ of WFHF and CFHF caused approximately 42.6% and 23.7% reduction, respectively. In addition, the extracts of H. fusiforme significantly reduced the expression levels of key pro-adipogenic transcription factors, including peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) and CCAAT/enhancer binding proteins ${\alpha}$ (C/$EBP{\alpha}$) and C/$EBP{\beta}$ as compared with controls. Accordingly, our data indicated that WFHF has a preeminent effect on inhibition of adipocyte differentiation among various extracts, and H. fusiforme extracts may be an ideal candidate for obesity relief.

• BMB Reports
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• v.51 no.1
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• pp.33-38
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• 2018

Sterol regulatory element-binding protein-1c (SREBP1c) plays an important role in triglyceride (TG) homeostasis. Although our previous study showed that hepatitis C virus core-binding protein 6 (HCBP6) regulates SREBP1c expression to maintain intracellular TG homeostasis, the mechanism underlying this regulation is unclear. In the present study, we found that HCBP6 increased intracellular TG levels by upregulating SREBP1c expression. HCBP6 increased SREBP1c transcription by directly binding to the SREBP1c promoter (at the -139- to +359-bp region). Moreover, we observed that HCBP6 interacted with $C/EBP{\beta}-binding$ site in the SREBP1c promoter both in vitro and in vivo. These results indicate that HCBP6 upregulates human SREBP1c expression by binding to the $C/EBP{\beta}-binding$ site in the SREBP1c promoter.