결정성 이산화티타늄 나노구조체의 제조, 특성평가 및 광전적 응용에 관한 연구

학위논문 (석사)-- 서울대학교 대학원 : 화학부(물리화학전공), 2014. 2. 장두전.Crystalline TiO2 nanostructures have been facilely grown on titanium foil via anodization and solvothermal processes and their morphological, structural, and optical properties have also been characterized. Photocatalytic and photovoltaic activities of TiO2 nanostructures have been measured using the degradation of an organic dye under Xe-lamp irradiation. Chapter 1 describes highly ordered and regularly porous anatase TiO2 nanotube arrays grown by anodizing Ti foil in mixed viscous solvents of ethylene glycol and glycerol. By changing the volume ratio of two solvents, we have controlled the structural and morphological properties of TiO2 nanotube arrays. Our prepared TiO2 nanotube arrays have been found to have enhanced (004) planes, which are reactive in catalysis reactions. Among our prepared samples, TiO2 nanotube arrays grown in 2:1 (v/v) ethylene glycol and glycerol have shown the best photocatalytic activity for the degradation of methylene blue and the highest photovoltaic conversion efficiency of 4.08%. Chapter 2 reports anatase-rutile cocrystalline TiO2 nanoblossoms fabricated via a one-step solvothermal process on Ti foil in mixed solvents of water and ethylene glycol. We have controlled the morphological, structural, and optical characteristics of TiO2 nanoblossoms easily by changing the volume ratio of water and ethylene glycol. Cocrystalline structures of our prepared TiO2 nanoblossoms act as nanoscale p-n junctions, which help to enhance the catalysis reactions. In particular, TiO2 nanoblossoms grown in the 1:1 volume mixture of water and ethylene glycol show the best photocatalytic activity.Abstract of Dissertation i List of Figures and Tables 1 Chapter 1. Facile Fabrication of Anatase TiO2 Nanotube Arrays Having High Photocatalytic and Photovoltaic Performances by Anodization of Titanium in Mixed Viscous Solvents 5 1.1. Abstract 6 1.2. Introduction 7 1.3. Experimental Section 10 1.4. Results and discussion 13 1.5. Conclusions 24 1.6. Acknowledgments 25 1.7. Supporting Information 26 1.8. References 28 Chapter 2. Enhanced Photocatalytic Performances of Cocrystalline TiO2 Nanoblossoms by the Effect of Nanoscale p-n Junctions 32 2.1. Abstract 33 2.2. Introduction 34 2.3. Experimental Section 37 2.4. Results and discussion 39 2.5. Conclusions 49 2.6. Acknowledgment 50 2.7. Supporting Information 51 2.8. References 53 Appendicies 57 A.1. List of Presentations 57 Abstract (Korean) 58Maste

PGC1 alpha Loss Promotes Lung Cancer Metastasis through Epithelial-Mesenchymal Transition

Simple Summary Despite the therapeutic advances, lung cancer is the most dangerous cancer with poor 5-year survival rate due to metastasis and recurrence. Accumulated evidence indicates that the epithelial-mesenchymal transition (EMT) is considered to be responsible for the lung cancer metastasis; however, the transcriptional frameworks that regulate EMT-related gene expression are still poorly understood. Here, we suggest that cooperation of TCF4-TWIST1 controlled by the PGC1 alpha-ID1 transcriptional axis mediates EMT and lung cancer metastasis, and that this molecular framework is an attractive target for lung cancer diagnosis and treatment. PGC1 alpha oppositely regulates cancer metastasis in melanoma, breast, and pancreatic cancer; however, little is known about its impact on lung cancer metastasis. Transcriptome and in vivo xenograft analysis show that a decreased PGC1 alpha correlates with the epithelial-mesenchymal transition (EMT) and lung cancer metastasis. The deletion of a single Pgc1 alpha allele in mice promotes bone metastasis of Kras(G12D)-driven lung cancer. Mechanistically, PGC1 alpha predominantly activates ID1 expression, which interferes with TCF4-TWIST1 cooperation during EMT. Bioinformatic and clinical studies have shown that PGC1 alpha and ID1 are downregulated in lung cancer, and correlate with a poor survival rate. Our study indicates that TCF4-TWIST1-mediated EMT, which is regulated by the PGC1 alpha-ID1 transcriptional axis, is a potential diagnostic and therapeutic target for metastatic lung cancer

Luteinizing hormone-dependent activation of the epidermal growth factor network is essential for ovulation

In the preovulatory ovarian follicle, mammalian oocytes are maintained in prophase meiotic arrest until the luteinizing hormone (LH) surge induces reentry into the first meiotic division. Dramatic changes in the somatic cells surrounding the oocytes and in the follicular wall are also induced by LH and are necessary for ovulation. Here, we provide genetic evidence that LH-dependent transactivation of the epidermal growth factor receptor (EGFR) is indispensable for oocyte reentry into the meiotic cell cycle, for the synthesis of the extracellular matrix surrounding the oocyte that causes cumulus expansion, and for follicle rupture in vivo. Mice deficient in either amphiregulin or epiregulin, two EGFR ligands, display delayed or reduced oocyte maturation and cumulus expansion. In compound-mutant mice in which loss of one EGFR ligand is associated with decreased signaling from a hypomorphic allele of the EGFR, LH no longer signals oocyte meiotic resumption. Moreover, induction of genes involved in cumulus expansion and follicle rupture is compromised in these mice, resulting in impaired ovulation. Thus, these studies demonstrate that LH induction of epidermal growth factor-like growth factors and EGFR transactivation are essential for the regulation of a critical physiological process such as ovulation and provide new strategies for manipulation of fertility. Copyright © 2007, American Society for Microbiology. All Rights Reserved

The PGE(2) EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice

Mice carrying a targeted disruption of the prostaglandin E-2 (PGE(2)) E-prostanoid receptor 3 (EP3) gene, Ptger3, were fed a high-fat diet (HFD), or a micronutrient matched control diet, to investigate the effects of disrupted PGE(2)-EP3 signaling on diabetes in a setting of diet-induced obesity. Although no differences in body weight were seen in mice fed the control diet, when fed a HFD, EP3(-/-) mice gained more weight relative to EP3(+/+) mice. Overall, EP3(-/-) mice had increased epididymal fat mass and adipocyte size; paradoxically, a relative decrease in both epididymal fat pad mass and adipocyte size was observed in the heaviest EP3(-/-) mice. The EP3(-/-) mice had increased macrophage infiltration, TNF-alpha, monocyte chemoattractant protein-1, IL-6 expression, and necrosis in their epididymal fat pads as compared with EP3(+/+) animals. Adipocytes isolated from EP3(+/+) or EP3(-/-) mice were assayed for the effect of PGE(2)-evoked inhibition of lipolysis. Adipocytes isolated from EP3(-/-) mice lacked PGE(2)-evoked inhibition of isoproterenol stimulated lipolysis compared with EP3(+/+). EP3(-/-) mice fed HFD had exaggerated ectopic lipid accumulation in skeletal muscle and liver, with evidence of hepatic steatosis. Both blood glucose and plasma insulin levels were similar between genotypes on a control diet, but when fed HFD, EP3(-/-) mice became hyperglycemic and hyperinsulinemic when compared with EP3(+/+) fed HFD, demonstrating a more severe insulin resistance phenotype in EP3(-/-). These results demonstrate that when fed a HFD, EP3(-/-) mice have abnormal lipid distribution, developing excessive ectopic lipid accumulation and associated insulin resistance

The THO complex is required for nucleolar integrity in Drosophila spermatocytes

The THO complex is a conserved multisubunit protein complex that functions in the formation of export-competent messenger ribonucleoprotein (mRNP). Although the complex has been studied extensively at the single-cell level, its exact role at the multicellular organism level has been poorly understood. Here, we isolated a novel Drosophila male sterile mutant, garmcho (garm). Positional cloning indicated that garm encodes a subunit of the Drosophila THO complex, THOC5. Flies lacking THOC5 showed a meiotic arrest phenotype with severe nucleolar disruption in primary spermatocytes. A functional GFP-tagged fusion protein, THOC5-GFP, revealed a unique pattern of THOC5 localization near the nucleolus. The nucleolar distribution of a testisspecific TATA binding protein (TBP)-associated factor (tTAF), SA, which is required for the expression of genes responsible for sperm differentiation, was severely disrupted in mutant testes lacking THOC5. But THOC5 appeared to be largely dispensable for the expression and nuclear export of either tTAF target mRNAs or tTAF-independent mRNAs. Taken together, our study suggests that the Drosophila THO complex is necessary for proper spermatogenesis by contribution to the establishment or maintenance of nucleolar integrity rather than by nuclear mRNA export in spermatocytes. © 2011. Published by The Company of Biologists Ltd

Cholesterol induces cardiac hypertrophy by activating the AKT pathway

Cardiac hypertrophy leads to decompensated heart function, predisposition to heart failure, and sudden death due to physiological and pathological stimuli. Although high cholesterol is considered a principal risk factor for atherosclerosis and heart disease, it has not been shown whether cholesterol itself is sufficient to cause cardiac hypertrophy. In this study, we investigated whether cholesterol induces cardiac hypertrophy, and identified cellular mechanisms underlying hypertrophic responses using H9c2 cells as a model system. Here we show that cholesterol loading significantly increased the cellular surface area and upregulated hypertrophy marker gene, β-myosin-heavy chain (β-MHC). Cholesterol loading alone activated the extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways. Conversely, cholesterol induced hypertrophic characteristic features such as increase in cellular surface area, and the expression of β-MHC mRNA is markedly inhibited by LY294002, a PI3K kinase inhibitor. These results suggest that cholesterol may play a key role in the development of cardiac hypertrophy through the activation of the PI3K/AKT pathway activation. © 2013 Elsevier Ltd. All rights reserved

Epiregulin-dependent amphiregulin expression and ERBB2 signaling are involved in luteinizing hormone-induced paracrine signaling pathways in mouse ovary

Sustained EGF receptor (EGFR) phosphorylation by de novo synthesis of EGFR ligands plays an essential role in mediating luteinizing hormone (LH)-induced ovulation process in the preovulatory follicles (POFs). In the present study, the effect of epiregulin (EREG) on oocyte maturation and ovulation was investigated using Ereg knockout (Ereg -/-) mice congenic on a C57BL/6 background. Rate of spontaneous oocyte meiotic resumption of denuded oocytes (DOs) or cumulus cell-oocyte complexes (COCs) in vitro is similar between wild-type and Ereg -/- mice. However, gonadotropin-induced meiotic resumption in vivo is attenuated, and the number of COCs with expanded cumulus matrix and superovulated eggs dramatically decrease in Ereg -/- mice. Nonetheless, the number of eggs ovulated during normal estrus cycles and litter sizes in Ereg -/- mice are comparable to those of wild-type littermates. In contrast to other EGFR ligands, induction of amphiregulin (Areg) mRNA is severely reduced in ovaries collected from Ereg -/- mice either after human chorionic gonadotropin (hCG) treatment in immature mice or LH surge in adults. Gonadotropin-induced EGFR and ERBB2 phosphorylation in ovaries is attenuated in immature Ereg -/- mice, and MAPK3/1 phosphorylation and prostaglandin synthase 2 (PTGS2) protein levels are reduced. This attenuation, however, is no longer detectable in adult Ereg -/- mice after LH surge. This study implicates that EREG mediates signals downstream of Areg mRNA expression and that EGFR-ERBB2 signals contributes to regulation of ovulation process. © 2011 Elsevier Inc

Arhgap17, a RhoGTPase activating protein, regulates mucosal and epithelial barrier function in the mouse colon

Coordinated regulation of the actin cytoskeleton by the Rho GTPase family is required for the maintenance of polarity in epithelial cells as well as for their proliferation and migration. A RhoGTPase-activating protein 17 (Arhgap17) is known to be involved in multiple cellular processes in vitro, including the maintenance of tight junctions and vesicle trafficking. However, the function of Arhgap17 has not been studied in the physiological context. Here, we generated Arhgap17-deficient mice and examined the effect in the epithelial and mucosal barriers of the intestine. Reporter staining revealed that Arhgap17 expression is limited to the luminal epithelium of intestine. Arhgap17-deficient mice show an increased paracellular permeability and aberrant localization of the apical junction complex in the luminal epithelium, but do not develop spontaneous colitis. The inner mucus layer is impervious to the enteric bacteria irrespective of Tff3 downregulation in the Arhgap17-deficient mice. Interestingly however, treatment with dextran sulfate sodium (DSS) causes an increased accumulation of DSS and TNF production in intraluminal cells and rapid destruction of the inner mucus layer, resulting in increased severity of colitis in mutant mice. Overall, these data reveal that Arhgap17 has a novel function in regulating transcellular transport and maintaining integrity of intestinal barriers

STAT3-mediatedMLST8gene expression regulates cap-dependent translation in cancer cells

Signal transducer and activator of transcription 3 (STAT3) regulates cell growth, cell survival, angiogenesis, metastasis of cancer cells, and cancer immune evasion by regulating gene expression as a transcription factor. However, the effect of STAT3 on translation is almost unknown. We demonstrated that STAT3 acts as a trans-acting factor forMLST8gene expression and the protein level of mLST8, a core component of mechanistic target of rapamycin complex 1 and 2 (mTORC1/2), positively regulates the mTORC1/2 downstream pathways. Suppression of STAT3 by siRNA attenuated 4E-BP1 phosphorylation, cap-dependent translation, and cell proliferation in a variety of cancer cells. In HCT116 cells,STAT3knockdown-induced decreases in 4E-BP1 and AKT phosphorylation levels were further attenuated byMLST8knockdown or recovered by mLST8 overexpression.STAT3knockdown-induced G2/M phase arrest was partially restored by co-knockdown of4EBP1, and the attenuation of cell proliferation was enhanced by the expression of an mTORC1-mediated phosphorylation-defective mutant of 4E-BP1. ChIP and promoter mapping using a luciferase reporter assay showed that the -951 to -894 bp ofMLST8promoter seems to include STAT3-binding site. Overall, these results suggest that STAT3-drivenMLST8gene expression regulates cap-dependent translation through 4E-BP1 phosphorylation in cancer cells