• Title/Summary/Keyword: ER${\alpha}$

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Effects of starvation-induced negative energy balance on endoplasmic reticulum stress in the liver of cows

  • Islam, Md Aminul;Adachi, Shuya;Shiiba, Yuichiroh;Takeda, Ken-ichi;Haga, Satoshi;Yonekura, Shinichi
    • Animal Bioscience
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    • v.35 no.1
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    • pp.22-28
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    • 2022
  • Objective: Endoplasmic reticulum (ER) stress engages the unfolded protein response (UPR) that serves as an important mechanism for modulating hepatic fatty acid oxidation and lipogenesis. Chronic fasting in mice induced the UPR activation to regulate lipid metabolism. However, there is no direct evidence of whether negative energy balance (NEB) induces ER stress in the liver of cows. This study aimed to elucidate the relationship between the NEB attributed to feed deprivation and ER stress in bovine hepatocytes. Methods: Blood samples and liver biopsy tissues were collected from 6 non-lactating cows before and after their starvation for 48 h. The blood non-esterified fatty acids (NEFA), β-hydroxybutyric acid (BHBA) and glucose level were analyzed. Real-time quantitative polymerase chain reaction and Western blotting were used to explore the regulation of genes associated with UPR and lipid metabolism. Results: The starvation increased the plasma BHBA and NEFA levels and decreased the glucose level. Additionally, the starvation caused significant increases in the mRNA expression level of spliced X-box binding protein 1 (XBP1s) and the protein level of phosphorylated inositol-requiring kinase 1 alpha (p-IRE1α; an upstream protein of XBP1) in the liver. The mRNA expression levels of peroxisome proliferator-activated receptor alpha and its target fatty acid oxidation- and ketogenesis-related genes were significantly upregulated by the starvation-mediated NEB. Furthermore, we found that the mRNA expression levels of lipogenic genes were not significantly changed after starvation. Conclusion: These findings suggest that in the initial stage of NEB in dairy cows, the liver coordinates an adaptive response by activating the IRE1 arm of the UPR to enhance ketogenesis, thereby avoiding a fatty liver status.

A Study on Temperature and Retaining Ion Effect on the Separation of Lanthanides (란탄계열원소들의 양이온교환분리에서의 온도와 보유이온의 영향에 관한 연구)

  • Young-Gu Ha;Bong-Il Ji
    • Journal of the Korean Chemical Society
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    • v.33 no.6
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    • pp.601-606
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    • 1989
  • The effects of temperature and retaining ion on the separation factor (${\alpha}$) and distribution ratio (D) of some lanthanides ($Pr^{3+},\;Nd^{3+},\;Sm^{3+},\;and\;Er^{3+}$) have been studied in the EDTA solution as an elutant by using Amberite IR 120 + resin. The retaining ions on the resin were ${NH_4}^+,\;Na^+,\;K^+,\;Mg^{2+},\;Ca^{2+},\;Zn^{2+}$and $Ce^{3+}$. Separation factor of Nd/Pr is much improved by using $Ce^{3+}$ as retaining ion. The distribution ratios were decreased with the increase of temperature, but separation factors did not always increase with the increase of temperature. However, in the case of $Ce^{3+}$ as retaining ion, separation factors of Nd/Pr and Sm/Nd were increased with the increasing of temperature. And also in the case of $Zn^{2+}$ as retaining ion, separation factor of Er/Sm was increased with the increasing of temperature.

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Effect of different provisional cement remnant cleaning procedures including Er:YAG laser on shear bond strength of ceramics

  • Zortuk, Mustafa;Gumus, Hasan Onder;Kilinc, Halil Ibrahim;Tuncdemir, Ali Riza
    • The Journal of Advanced Prosthodontics
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    • v.4 no.4
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    • pp.192-196
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    • 2012
  • PURPOSE. The purpose of this study was to evaluate the effect of provisional cement removal by different dentin cleaning protocols (dental explorer, pumice, cleaning bur, Er:YAG laser) on the shear bond strength between ceramic and dentin. MATERIALS AND METHODS. In total, 36 caries-free unrestored human third molars were selected as tooth specimens. Provisional restorations were fabricated and cemented with eugenol-free provisional cement. Then, disc-shaped ceramic specimens were fabricated and randomly assigned to four groups of dentin cleaning protocols (n = 9). Group 1 (control): Provisional cements were mechanically removed with a dental explorer. Group 2: The dentin surfaces were treated with a cleaning brush with pumice Group 3: The dentin surfaces were treated with a cleaning bur. Group 4: The provisional cements were removed by an Er:YAG laser. Self-adhesive luting cement was used to bond ceramic discs to dentin surfaces. Shear bond strength (SBS) was measured using a universal testing machine at a 0.05 mm/min crosshead speed. The data were analyzed using a Kolmogorov Smirnov, One-way ANOVA and Tukey HSD tests to perform multiple comparisons (${\alpha}$=0.05). RESULTS. The dentin cleaning methods did not significantly affect the SBS of ceramic discs to dentin as follows: dental explorer, pumice, cleaning bur, and Er:YAG laser. CONCLUSION. The use of different cleaning protocols did not affect the SBS between dentin and ceramic surfaces.

Potential Therapeutic Targets for the Primary Gallbladder Carcinoma: Estrogen Receptors

  • Zhang, Ling-Qiang;Zhang, Xiu-De;Xu, Jia;Wan, Yong;Qu, Kai;Zhang, Jing-Yao;Wang, Zhi-Xin;Wei, Ji-Chao;Meng, Fan-Di;Tai, Ming-Hui;Zhou, Lei;Liu, Chang
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2185-2190
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    • 2013
  • Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

In Silico Docking Studies of Selected Flavonoids - Natural Healing Agents against Breast Cancer

  • Suganya, Jeyabaskar;Radha, Mahendran;Naorem, Devi Leimarembi;Nishandhini, Marimuthu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.19
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    • pp.8155-8159
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    • 2014
  • Background: Breast cancer is the serious health concern in India causing the highest mortality rate in females, which occurs due to uncontrolled cell division and can be metastasize to other parts of the human body. Interactions with estrogen receptor (ER) alpha are mainly responsible for the malignant tumors with regulation of the transcription of various genes as a transcription factor. Most of the drugs currently used for the breast cancer treatment produce various side effects and hence we focused on natural compounds which do not exhibit any toxic effect against normal human cells. Materials and Methods: Structure of human ER was retrieved from the Protein Data Bank and the structures of flavonoid compounds have been collected from PubChem database. Molecular docking and drug likeness studies were performed for those natural compounds to evaluate and analyze the anti-breast cancer activity. Results: Finally two compounds satisfying the Lipinski's rule of five were reported. The two compounds also exhibited highest binding affinity with human ER greater than 10.5 Kcal/mol. Conclusions: The results of this study can be implemented in the drug designing pipeline.

Study on the Estrogen Receptor Mediated Toxicity of Cadmium and Protective Effects of Antioxidant (에스트로겐 수용체를 통한 카드뮴 독성 및 항산화제에 의한 독성경감에 관한 연구)

  • Kim Tae-Sung;Kang Tae-Seok;Kang Ho-Il;Moon Hyun-Ju;Kang Il-Hyun;Lee Young-Joo;Choi Eun-Hee;Hong Jin-Tae;Han Soon-Young;Hong Jin-Hwan
    • Environmental Mutagens and Carcinogens
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    • v.26 no.1
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    • pp.12-19
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    • 2006
  • Cadmium, a human carcinogen, can induce toxicity in various cell lines and organs. Despite extensive research, the mechanisms of cadmium-induced cell toxicity and estrogenic potential in human are not clear. This study was performed to investigate cadmium-induced toxicity on human breast cancer cells: MCF-7 cells, an estrogen receptor (ER) positive breast cancer cells, and MDA-MB-231 cells, an ER negative breast cancer cells. MCF-7 cells was proved to be more sensitive than the other cell lines (IC50 = $50\;{\mu}M$ at MCF-7 cells and $120{\mu}M$ at MDA-MB-231). The expression of JNK and AP-1 transcription factors such as c-Jun and c-Fos dependent transcription were increased by cadmium treatment. Inhibition of ER activation by ER antagonist (tamoxifen or ICI 182,780) significantly recovered the viablity and inhibited apoptotic cell death. This suggested that cadmium-induced cell death in ER (+) cells was mediated by JNK/AP-1 pathway and this pathway was more stimulated by ER activated by cadmium. Co-treatment of antioxidants such as selenium (Se), butylated hydroxyanisole (BHA), glutathione (GSH), or N-acetyl-L-cysteine (NAC) recovered the cadmium-induced cell death in MCF-7 cells. Cadmium-induced lipid peroxidation was decreased by GSH, NAC, or BHA in MCF-7 cells. The expression of SOD protein was decreased by cadmium ($100{\mu}M$) but recovered by GSH, NAC, BHA, or Se. Our data showed that the cadmium-induced cell toxicity in human breast cancer cells could be protected by the antioxidants (Se, BHA, NAC, GSH, or NAC) and ER antagonist (tamoxifen or ICI 182,780). Therefore, toxicity of cadmium in breast cancer were mediated by oxidative stress and $ER{\alpha}$.

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1,25-dihydroxyvitamin D3 affects thapsigargin-induced endoplasmic reticulum stress in 3T3-L1 adipocytes

  • Dain Wi;Chan Yoon Park
    • Nutrition Research and Practice
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    • v.18 no.1
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    • pp.1-18
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    • 2024
  • BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) alleviates ER stress in adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)2D3 after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS: Treatment with 1,25(OH)2D3 during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)2D3 treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)2D3 administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)2D3 inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)2D3 treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS: Our data suggest that 1,25(OH)2D3 prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.

Expression of Beta-catenin-interacting Protein 1 (CTNNBIP1) Gene Is Increased under Hypothermia but Decreased under Additional Ischemia Conditions

  • Kwon, Kisang;Kim, Seung-Whan;Yu, Kweon;Kwon, O-Yu
    • Biomedical Science Letters
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    • v.20 no.3
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    • pp.168-172
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    • 2014
  • It has recently been shown that hypothermia treatment improves brain ischemia injury and is being increasingly considered by many clinicians. However, the precise roles of hypothermia for brain ischemia are not yet clear. In the present study we demonstrated firstly that hypothermia induced beta-catenin-interacting protein 1 (CTNNBIP1) gene expression and its expression was dramatically decreased under ischemic conditions. It was also demonstrated that hypothermia activated endoplasmic reticulum (ER) stress sensors especially both, the phosphorylation of $eIF2{\alpha}$, and ATF6 proteolytic cleavage. However, the factors of apoptosis and autophagy were not associated with hypothermia. These findings suggested that hypothermia controlled CTNNBIP1 gene expression under ischemia, which may provide a clue to the development of treatments and diagnostic methods for brain ischemia.

Evaluation of 1-DNJ extracted from Silkworm in GBV-B Infected Marmoset Hepatocytes

  • James R. Jacob;Yoo, Jung-Eun;Seong, Su-Il;Ryu, Kang-Sun;Kim, Young-Ho
    • Proceedings of the Korean Society of Sericultural Science Conference
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    • 2003.04a
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    • pp.53-53
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    • 2003
  • Alpha-glucosidase inhibitor, 1-deoxynojirimycin, has been shown to eliminate the production of ER-budding viruses in the ER of host cell. This glucose-derived iminosugar derivative, 1-DNJ, has been largely purified from midgut of silkworm, Bombyx mori, Here, we have screened the antiviral activity in the GBV-B infected marmoset hepatocyte cell line. (omitted)

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Optical, Mechanical and Tribological Properties of $Y_2O_3$ $Er_2O_3$ and $Nd_2O_3$ Doped Polycrystalline Silicon Nitride Ceramics

  • Joshi, Bhupendra;Lee, Su-Wan
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2010.05a
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    • pp.51.1-51.1
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    • 2010
  • $Y_2O_3$ $Er_2O_3$ and $Nd_2O_3$ doped polycrystalline silicon nitride were prepared by hot pressed sintering at $1850^{\circ}C$ and their optical transmittance were investigated in visible and in infrared region. Mechanical and tribological properties were also investigated. Grain growth in silicon nitride was reduced with addition of $Y_2O_3$ and $Nd_2O_3$. 1 wt.% of each rare earth metal were sintered with 3 wt.% MgO, 9wt.% AlN and 87 wt.% of ${\alpha}-Si_3N_4$. Adding these rare earth metal oxides shows good mechanical properties as high strength and toughness and also shows low friction coefficient.

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