• Title/Summary/Keyword: ER-${\alpha}$

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Prediction and Analysis of Ligands against Estrogen Related Receptor Alpha

  • Chitrala, Kumaraswamy Naidu;Yeguvapalli, Suneetha
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2371-2375
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    • 2013
  • Breast cancer is one of the most common malignancies in women around the world. Among the various hormonal types of breast cancer, those that are estrogen receptor (ER) positive account for the majority. Among the estrogen related receptors, estrogen related receptor ${\alpha}$ is known to have a potential role in breast cancer and is one of the therapeutic target. Hence, prediction of novel ligands interact with estrogen related receptor alpha is therapeutically important. The present study, aims at prediction and analysis of ligands from the KEGG COMPOUND database (containing 10,739 entries) able to interact against estrogen receptor alpha using a similarity search and molecular docking approach.

The Distributions of Three Genetic Polymorphisms in the Estrogen $Receptor-\alpha$ Gene in Korean Essential Hypertensives (한국인 본태성 고혈압군에서 에스트로젠 수용체-$\alpha$(유전자에 존재하는 다형성의 분포에 관한 연구)

  • Kim Ji Young;Kang Byung Yong;Lee Kang Oh
    • Environmental Analysis Health and Toxicology
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    • v.20 no.3 s.50
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    • pp.249-258
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    • 2005
  • Blood pressure, obesity and bone mineral density are multifactorial traits influenced by genetic factor. The purpose of this study was to clarify the association between three genetic polymorphisms in the estrogen receptor-$\alpha$ (ER -$\alpha$) gene and essential hypertension in korean population. One hundred and seventy-one people including 90 normotensives and 81 essential hypertentives were recruited. Among genetic polymorphisms studied, the Xba I RFLP in the intron 1 of this gene polymorphism was significantly associated with essential hypertension in women, suggesting the sexual dimorphism in genetic effect (P (<) 0.05). Further studied suggest that a larger sample size of this study are needed.

Pre-initiation treatment of indole-3-carbinol(I3C) inhibits 7,12-Dimethylbenz[α] anthracene(DMBA)-induced rat mammary carcinogenesis (Indole-3-carbinol(I3C) 투여에 의한 7,12-Dimethylbenz[α] anthracene(DMBA) 유발 랫드 유선발암 억제)

  • Kang, Jin Seok;Ahn, Byeongwoo;Nam, Ki Taek;Choi, Mina;Kim, Ji Young;Kim, Dae Joong;Jang, Dong Deuk;Yang, Ki-Hwa
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.549-555
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    • 2001
  • Indole-3-carbinol (I3C), one component of cruciferous vegetables (the Fammily of Cruciferae), has been shown to exert its chemopreventive effect in liver, colon and mammary tissue before or concurrent exposure of carcinogen, but there have been several evidences that consumption of I3C induced tumor promotion in some tissues. Our studies were investigated to examine the modifying effects of I3C in the 7,12-dimethylbenz[$\alpha$]anthracene (DMBA) induced rat mammary gland tumor model. Fifty-two female Sprague-Dawley rats were randomly divided into five groups. Animals of the group 1 were given the diet containing 100ppm I3C and animals of the groups 2 and 4 were given the diet containing 300ppm I3C from 6 weeks of age. At 7 weeks of age, the animals of the groups 1, 2 and 3 were intubated with DMBA. All amimals were killed at 20 weeks after carcinogen treatment. There were significant increases of food consumption in I3C feeding groups compared with those of basal diet feeding groups. The incidences of the mammary tumors in the group 1, 2 and 3 were 75.0% (9/12), 56.3% (9/16) and 93.8% (15/16), respectively and the average number of tumors of group 1 (DMBA+I3C 100ppm: $2.08{\pm}0.61$) and 2 (DMBA+I3C 300ppm: $1.19{\pm}0.32$) were significantly lower than that of group 3 (DMBA alone: $4.63{\pm}0.72$) at the value of P<0.05 and P<0.001, respectively. In the pathological examination of appearing tumors, most of them were adenocarcinoma. Many epithelial cells of tumors showed strong estrogen receptor (ER) $\alpha$ expression but there were slight difference of ER $\alpha$ expression among the type of tumors. We suggest that pre-initiation treatment of I3C has an inhibitory effects on mammary carcinogenesis induced by DMBA.

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Estrogen Induces CK2α Activation via Generation of Reactive Oxygen Species

  • Jeong, Soo-Yeon;Im, Suhn-Young
    • Biomedical Science Letters
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    • v.25 no.1
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    • pp.23-31
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    • 2019
  • The protein kinase $CK2{\alpha}$ (formerly Casein Kinase II) is implicated in tumorigenesis and transformation. However, the mechanisms of $CK2{\alpha}$ activation in breast cancer have yet to be elucidated. This study investigated the mechanisms of $CK2{\alpha}$ activation in estrogen signaling. Estrogen increased reactive oxygen species (ROS) production, $CK2{\alpha}$ activity, and protein expression in estrogen receptor positive ($ER^+$) MCF-7 human breast cancer cells, which were inhibited by the antioxidant N-acetyl-L-cysteine. $H_2O_2$ enhanced $CK2{\alpha}$ activity and protein expression. Human epidermal growth factor (EGF) increased ROS production, $CK2{\alpha}$ activity and protein expression in EGF receptor 2 (HER2)-overexpressing MCF-7 (MCF-7 HER2) cells, but not in MCF-7 cells. Estrogen induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The p38 inhibitor, SB202190, blocked estrogen-induced increases in ROS production, $CK2{\alpha}$ activity and $CK2{\alpha}$ protein expression. The data suggest that ROS/p38 MAPK is the key inducer of $CK2{\alpha}$ activation in response to estrogen or EGF.

Effect of Medicinal Herb Prepared through Traditional Antidiabetic Prescription on α-Glucosidase Activity and Evaluation Method for Anti-Melanogenesis Agents Using α-Glucosidase Activity (당뇨 처방에 근거한 생약재의 α-Glucosidase 활성 저해 효과 및 이를 활용한 미백 소재 평가법)

  • Kim, Mi Jin;Im, Kyung Ran;Yoon, Kyung-Sup
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.7
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    • pp.993-999
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    • 2015
  • For the purpose of investigating the in vitro antidiabetic activity of a medicinal herb and herb mixture extracts prepared through traditional antidiabetic prescription, this study examined ${\alpha}$-glucosidase inhibitory activity. Tyrosinase, a type I membrane glycoprotein, is synthesized and glycosylated in the endoplasmic reticulum (ER) and Golgi. The enzyme is subsequently transported to melanosomes, where it participates in melanogenesis. Previous studies showed that disruption of early ER N-glycan processing by an ${\alpha}$-glucosidase inhibitor suppresses tyrosinase enzymatic activity and melanogenesis. According to the results, most oriental medicinal herbal extracts were stronger than acarbose and N-butyldeoxynojirimycin, known as an ${\alpha}$-glucosidase inhibitor. Interestingly, ethyl acetate layer of enzyme hydrolyzed Cheongsimyeonjaeum had an inhibitory effect on melanin synthesis in B16F1 cells, although it did not inhibit tyrosinase activity directly. Together, ${\alpha}$-glucosidase inhibition activity could be used to evaluate anti-melanogenesis, although cross-checking with melanin inhibitory assay is recommended.

Effects of Dendropanax morbifera extracts on postmenopausal syndrome in ovariectomized rats (황칠추출분말이 난소적출 흰쥐의 여성 갱년기 증상에 미치는 영향)

  • Oh, Ga-hui;Oh, Sung-moon;Lee, Seung-sik;Kim, Ji-hyeon;Oh, Jueon;Park, Young-joon;Kim, Joo-eun
    • Korean Journal of Food Science and Technology
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    • v.51 no.4
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    • pp.361-368
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    • 2019
  • The present study aimed to evaluate the effect of Dendropanax morbifera (DM) extract on postmenopausal syndrome and to develop DM extract as an alternative for hormonal therapy. The following seven groups of rats; normal control (sham), ovariectomized (OVX) control, Punica granatum (PG)-treated group (770 mg/kg), estradiol treated group (0.5 mg/kg), and three DM-treated groups (200, 500, 1000 mg/kg) were compared. Indicated compounds were administrated once a day for eight weeks. To evaluate the estrogenic effect of DM extract, western blot analysis was performed on the liver tissue to confirm the expression of estrogen receptor ($ER-{\alpha}$, $ER-{\beta}$). Our analysis showed that after DM administration, collagen cross-linked C-telopeptide (CTX) value decreased while $ER-{\alpha}$ protein expression increased in a dose-dependent manner through the MAPK/ERK pathway in OVX rats. These results suggest that Dendropanax morbifera exerts estrogenic effect by inducing estrogen receptor expression and activating MAPK/ERK pathway.

The effect of heat stress on frame switch splicing of X-box binding protein 1 gene in horse

  • Lee, Hyo Gun;Khummuang, Saichit;Youn, Hyun-Hee;Park, Jeong-Woong;Choi, Jae-Young;Shin, Teak-Soon;Cho, Seong-Keun;Kim, Byeong-Woo;Seo, Jakyeom;Kim, Myunghoo;Park, Tae Sub;Cho, Byung-Wook
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.8
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    • pp.1095-1103
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    • 2019
  • Objective: Among stress responses, the unfolded protein response (UPR) is a well-known mechanism related to endoplasmic reticulum (ER) stress. ER stress is induced by a variety of external and environmental factors such as starvation, ischemia, hypoxia, oxidative stress, and heat stress. Inositol requiring enzyme $1{\alpha}$ ($IRE1{\alpha}$)-X-box protein 1 (XBP1) is the most conserved pathway involved in the UPR and is the main component that mediates $IRE1{\alpha}$ signalling to downstream ER-associated degradation (ERAD)- or UPR-related genes. XBP1 is a transcription factor synthesised via a novel mechanism called 'frame switch splicing', and this process has not yet been studied in the horse XBP1 gene. Therefore, the aim of this study was to confirm the frame switch splicing of horse XBP1 and characterise its dynamics using Thoroughbred muscle cells exposed to heat stress. Methods: Primary horse muscle cells were used to investigate heat stress-induced frame switch splicing of horse XBP1. Frame switch splicing was confirmed by sequencing analysis. XBP1 amino acid sequences and promoter sequences of various species were aligned to confirm the sequence homology and to find conserved cis-acting elements, respectively. The expression of the potential XBP1 downstream genes were analysed by quantitative real-time polymerase chain reaction. Results: We confirmed that splicing of horse XBP1 mRNA was affected by the duration of thermal stress. Twenty-six nucleotides in the mRNA of XBP1 were deleted after heat stress. The protein sequence and the cis-regulatory elements on the promoter of horse XBP1 are highly conserved among the mammals. Induction of putative downstream genes of horse XBP1 was dependent on the duration of heat stress. We confirmed that both the mechanisms of XBP1 frame switch splicing and various binding elements found in downstream gene promoters are highly evolutionarily conserved. Conclusion: The frame switch splicing of horse XBP1 and its dynamics were highly conserved among species. These results facilitate studies of ER-stress in horse.

Apolipoprotein E in Synaptic Plasticity and Alzheimer's Disease: Potential Cellular and Molecular Mechanisms

  • Kim, Jaekwang;Yoon, Hyejin;Basak, Jacob;Kim, Jungsu
    • Molecules and Cells
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    • v.37 no.11
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    • pp.767-776
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    • 2014
  • Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

Gomisin A Ameliorates Endoplasmic Reticulum Stress-induced Hepatic Steatosis (Gomisin A의 비알코올성 지방간 보호효과)

  • Yun, Ye-Rang;Jung, Myeong Ho
    • Journal of Life Science
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    • v.27 no.2
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    • pp.233-240
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    • 2017
  • Previously, we have shown that Schisandra chinensis (Turcz.) Baill. (S. chinensis) has a protective effect against endoplasmic reticulum (ER) stress-induced hepatic steatosis. Gomisin A is a bioactive phytoestrogen derived from S. chinensis. In the present study, the in vitro and in vivo effects of gomisin A on ER stress and hepatic steatosis were investigated. We quantified the expression of markers of ER stress, including glucose regulated protein 78 (GRP78), C/EBP homolog protein (CHOP), and X-box-binding protein-1 (XBP-1), in HepG2 cells treated with tunicamycin or palmitate. Tunicamycin treatment in HepG2 cells induced the expression of markers of ER stress, including GRP78, CHOP, and XBP-1c. However, treatment with gomisin A reduced the expression of markers of ER stress. These inhibitory effects were also observed in palmitate-incubated HepG2 cells. The in vivo inhibitory effects of gomisin A were assessed in mice injected with tunicamycin or fed with a high fat diet (HFD). Gomisin A reduced the expression of markers of ER stress and decreased triglyceride levels in the livers of mice after tunicamycin injection or HFD feeding. Furthermore, gomisin A decreased the expression of inflammatory genes in palmitate-incubated HepG2 cells and the liver of HFD-fed obese mice. These results suggest that gomisin A inhibits ER stress and ameliorates hepatic steatosis induced by ER stress.

Cell Death and Stress Signaling in Glycogen Storage Disease Type I

  • Kim, So Youn;Bae, Yun Soo
    • Molecules and Cells
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    • v.28 no.3
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    • pp.139-148
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    • 2009
  • Cell death has been traditionally classified in apoptosis and necrosis. Apoptosis, known as programmed cell death, is an active form of cell death mechanism that is tightly regulated by multiple cellular signaling pathways and requires ATP for its appropriate process. Apoptotic death plays essential roles for successful development and maintenance of normal cellular homeostasis in mammalian. In contrast to apoptosis, necrosis is classically considered as a passive cell death process that occurs rather by accident in disastrous conditions, is not required for energy and eventually induces inflammation. Regardless of different characteristics between apoptosis and necrosis, it has been well defined that both are responsible for a wide range of human diseases. Glycogen storage disease type I (GSD-I) is a kind of human genetic disorders and is caused by the deficiency of a microsomal protein, glucose-6-phosphatase-${\alpha}$ ($G6Pase-{\alpha}$) or glucose-6-phosphate transporter (G6PT) responsible for glucose homeostasis, leading to GSD-Ia or GSD-Ib, respectively. This review summarizes cell deaths in GSD-I and mostly focuses on current knowledge of the neutrophil apoptosis in GSD-Ib based upon ER stress and redox signaling.