• Title/Summary/Keyword: Homer1

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Deficiencies of Homer2 and Homer3 accelerate aging-dependent bone loss in mice

  • Kang, Jung Yun;Kang, Namju;Shin, Dong Min;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.45 no.3
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    • pp.126-133
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    • 2020
  • Homer proteins are scaffold proteins that regulate calcium (Ca2+) signaling by modulating the activity of multiple Ca2+ signaling proteins. In our previous report, Homer2 and Homer3 regulated NFATc1 function through its interaction with calcineurin, which then acted to regulate receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and bone metabolism. However, to date, the role of Homers in osteoclastogenesis remains unknown. In this study, we investigated the roles of Homer2 and Homer3 in aging-dependent bone remodeling. Deletion of Homer2/Homer3 (Homer2/3 DKO) markedly decreased the bone density of the femur. The decrease in bone density was not seen in mice with Homer2 (Homer2-/-) and Homer3 (Homer3-/-) deletion. Moreover, RANKL treatment of bone marrow-derived monocytes/macrophages in Homer2/3 DKO mice significantly increased the formation of multinucleated cells and resorption areas. Finally, Homer2/3 DKO mice decreased bone density in an aging-dependent manner. These findings suggest a novel potent mode of bone homeostasis regulation through osteoclasts differentiation during aging by Homer proteins, specifically Homer2 and Homer3.

Regulation of the expression and function of TRPCs and Orai1 by Homer2 in mouse pancreatic acinar cells

  • Kang, Jung Yun;Kang, Namju;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.46 no.3
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    • pp.134-139
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    • 2021
  • Under physiological conditions, calcium (Ca2+) regulates essential functions of polarized secretory cells by the stimulation of specific Ca2+ signaling mechanisms, such as increases in intracellular Ca2+ concentration ([Ca2+]i) via the store-operated Ca2+ entry (SOCE) and the receptor-operated Ca2+ entry (ROCE). Homer proteins are scaffold proteins that interact with G protein-coupled receptors, inositol 1,4,5-triphosphate (IP3) receptors, Orai1-stromal interaction molecule 1, and transient receptor potential canonical (TRPC) channels. However, their role in the Ca2+ signaling in exocrine cells remains unknown. In this study, we investigated the role of Homer2 in the Ca2+ signaling and regulatory channels to mediate SOCE and ROCE in pancreatic acinar cells. Deletion of Homer2 (Homer2-/-) markedly increased the expression of TRPC3, TRPC6, and Orai1 in pancreatic acinar cells, whereas these expressions showed no difference in whole brains of wild-type and Homer2-/- mice. Furthermore, the response of Ca2+ entry by carbachol also showed significant changes to the patterns regulated by specific blockers of SOCE and ROCE in pancreatic acinar cells of Homer2-/- mice. Thus, these results suggest that Homer2 plays a critical role in the regulatory action of the [Ca2+]i via SOCE and ROCE in mouse pancreatic acinar cells.

Regulatory mechanisms of the store-operated Ca2+ entry through Orai1 and STIM1 by an adaptor protein in non-excitable cells

  • Kang, Jung Yun;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.47 no.3
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    • pp.33-40
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    • 2022
  • Store-operated Ca2+ entry (SOCE) represents one of the major Ca2+ entry routes in non-excitable cells. It is involved in a variety of fundamental biological processes and the maintenance of Ca2+ homeostasis. The Ca2+ release-activated Ca2+ (CRAC) channel consists of stromal interaction molecule and Orai; however, the role and action of Homer proteins as an adaptor protein to SOCE-mediated Ca2+ signaling through the activation of CRAC channels in non-excitable cells still remain unknown. In the present study, we investigated the role of Homer2 in the process of Ca2+ signaling induced by the interaction between CRACs and Homer2 proteins in non-excitable cells. The response to Ca2+ entry by thapsigargin-mediated Ca2+ store depletion remarkably decreased in pancreatic acinar cells of Homer2-/- mice, as compared to wild-type cells. It also showed critical differences in regulated patterns by the specific blockers of SOCE in pancreatic acinar cells of Homer2-/- mice. The response to Ca2+ entry by the depletion in Ca2+ store markedly increased in the cellular overexpression of Orai1 and STIM1 as compared to the overexpression of Homer2 in cells; however, this response was remarkably inhibited by the overexpression of Orai1, STIM1, and Homer2. These results suggest that Homer2 has a critical role in the regulatory action of SOCE activity and the interactions between CRAC channels.

Identification of Homer1 as a Potential Prognostic Marker for Intrahepatic Cholangiocarcinoma

  • Wu, San-Yun;Yu, Ming-Xia;Li, Xiao-Gai;Xu, Shu-Fang;Shen, Ji;Sun, Zhen;Zhou, Xin;Chen, Xing-Zhen;Tu, Jian-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3299-3304
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    • 2014
  • Background: The aim of the present study was to analyze whether Homer1 is a potential prognostic marker for intrahepatic cholangiocarcinoma (ICC). Materials and Methods: The expression of Homer1 in ICC tissue was detected with immunohistochemistry and levels of protein in ICC and paratumor tissues were evaluated by Western blotting. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. Results: Homer1 expression was high in 67.4% (58/86) of ICC samples, and there was significant difference between ICC and adjacent noncancerous tissues (p<0.001); high expression was associated with poor histologic differentiation (p=0.019), TNM stage (p=0.014), lymph node metastasis (p=0.040), and lymphatic invasion (p=0.025). On Kaplan-Meier analysis, a comparison of survival curves of low versus high expressors of Homer1 revealed a highly significant difference in OS (p=0.001) and DFS (p=0.006), indicating that high expression of Homer1 was linked with a worse prognosis. Multivariate analyses showed that Homer1 expression was an independent risk factor predicting overall survival[Hazard ratio(HR), 7.52; 95% confidence interval (CI), 2.63-21.47; p=0.002] and disease-free survival (HR, 11.56; 95%CI, 5.17-25.96; p<0.001) in ICC. Conclusions: Homer1 promotes lymphatic invasion and associates with lymph node metastasis and poor prognosis of ICC. The current study shows that Homer1 may be an independent prognostic factor for ICC patients after curative resection, and it provides an important basis for screening/treating high-risk patients.

Growth and Differentiation Effects of Homer3 on a Leukemia Cell Line

  • Li, Zheng;Qiu, Hui-Ying;Jiao, Yang;Cen, Jian-Nong;Fu, Chun-Mei;Hu, Shao-Yan;Zhu, Ming-Qing;Wu, De-Pei;Qi, Xiao-Fei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2525-2528
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    • 2013
  • The Homer protein family, also known as the family of cytoplasmic scaffolding proteins, which include three subtypes (Homer1, Homer2, Homer3). Homer3 can regulate transcription and play a very important role in the differentiation and development for some tissues (e.g. muscle and nervous systems). The current studies showed that Homer3 abnormal expression changes in acute myeloid leukemia (AML). Forced expression of Homer3 in transfected K562 cells inhibited proliferation, influenced the cell cycle profile, affected apoptosis induced by $As_2O_3$ through inhibition of Bcl2 expression, and also promoted cell differentiation induced by 12-O-tetra decanoylphorbol-acetate (TPA). These results showed that Homer3 is a novel gene which plays a certain role in the occurrence and development of AML.

Homer2 regulates amylase secretion via physiological calcium oscillations in mouse parotid gland acinar cells

  • Kang, Namju;Kang, Jung Yun;Shin, Dong Min;Yang, Yu-Mi
    • International Journal of Oral Biology
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    • v.45 no.2
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    • pp.58-63
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    • 2020
  • The salivary glands secrete saliva, which plays a role in the maintenance of a healthy oral environment. Under physiological conditions, saliva secretion within the acinar cells of the gland is regulated by stimulation of specific calcium (Ca2+) signaling mechanisms such as increases in the intracellular Ca2+ concentration ([Ca2+]i) via storeoperated Ca2+ entry, which involves components such as Orai1, transient receptor potential (TRP) canonical 1, stromal interaction molecules, and inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs). Homer proteins are scaffold proteins that bind to G protein-coupled receptors, IP3Rs, ryanodine receptors, and TRP channels. However, their exact role in Ca2+ signaling in the salivary glands remains unknown. In the present study, we investigated the role of Homer2 in Ca2+ signaling and saliva secretion in parotid gland acinar cells under physiological conditions. Deletion of Homer2 (Homer2-/-) markedly decreased the amplitude of [Ca2+]i oscillations via the stimulation of carbachol, which is physiologically concentrated in parotid acinar cells, whereas the frequency of [Ca2+]i oscillations showed no difference between wild-type and Homer2-/- mice. Homer2-/- mice also showed a significant decrease in amylase release by carbachol in the parotid gland in a dose-dependent manner. These results suggest that Homer2 plays a critical role in maintaining [Ca2+]i concentration and secretion of saliva in mouse parotid gland acinar cells.

Optimization of Residential Photovoltaic-Fuel Cell Hybrid System Using HOMER(R) (HOMER를 이용한 가정용 태양광-연료전지 하이브리드시스템의 운전 최적화)

  • Park, Se-Joon;Li, Ying;Choi, Young-Sung;Lee, Kyung-Sup
    • The Transactions of the Korean Institute of Electrical Engineers P
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    • v.59 no.1
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    • pp.129-133
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    • 2010
  • A hybrid system which is combined several complementary new and renewable power sources, such as photovoltaic, fuel-cell, and wind generator, etc., has been presented in various approaches. For instance, a photovoltaic cannot always generate stable output power with ever-changing weather condition, so it might be co-generated with a wind generator, diesel generator, and some other sources. In this paper, a residential PV-FC hybrid system is suggested as a distribution power source, and its operation is optimized by HOMER$^{(R)}$. As a result, it is the most economic that 5[kW] PV, 1[kW] FC, 4 batteries, 2[kW] electrolyzer, 0.5[kg] $H_2$ tank, 3[kW] converter are applied to the hybrid system.

Analysis of Size and Economic Sensitivities according to Changes in Component Replacing Costs of Renewable Hybrid Generation System (신재생복합발전시스템의 각 구성품 교체비용변화에 따른 용량 및 경제성 민감도 분석)

  • Lim, Jong Hwan
    • Transactions of the Korean Society of Mechanical Engineers B
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    • v.39 no.1
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    • pp.71-78
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    • 2015
  • This paper presents a method for analyzing the size and economic sensitivity of a new renewable hybrid generation system according to changes in the component replacement costs based on HOMER (Hybrid Optimization Model for Electric Renewables). The design of a hybrid system can be optimized by reducing the size of a sensitive component based on sensitivity analysis using the change in cost of a component. Sensitivity analysis can also provide information on what combinations are necessary for the optimal hybrid system. As an example, sensitivity analysis was performed on the residential load provided by HOMER, and the effects of component replacement costs on the system size and cost were quantitatively analyzed.

Economical Feasibility Evaluation of Solar-Fuel Cells in Hybrid Energy System for Domestic Electricity Demands (가정의 전기 수요를 고려한 태양전지-연료전지 하이브리드 에너지시스템의 경제성 평가)

  • Li, Ying;Choi, Young-Sung;Zhang, You-Sai;Lee, Kyung-Sup
    • The Transactions of the Korean Institute of Electrical Engineers P
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    • v.59 no.1
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    • pp.117-122
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    • 2010
  • The solar cells and fuel cells power are being encouraged to reduce the environmental pollution and combat the global warming. And the electric generation hybrid system is usually more reliable and less costly than the systems that use a single source of energy. HOMER provides a platform to design and simulate the power system and then to choose the optimization results. Based on the electricity demand conditions during a year, this paper simulates with the HOMER and performs the monthly average electrical production and the most feasible economical case includes the net present costs and the annualized costs of the hybrid system components.

Economic Analysis of Grid-connected Microgrid of Industrial Complex Using Homer (Homer를 이용한 산업단지 계통연계 마이크로그리드 경제성 분석)

  • Na, Jeong-Sueng;Son, Nam-Rye;Yang, Hyun-Chang;Yang, Seung-Hak
    • Proceedings of the KIPE Conference
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    • 2019.11a
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    • pp.236-238
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    • 2019
  • 국내 마이크로그리드는 실증단지, 도서지역, 캠퍼스, 산업단지등에 구축되고 있다. 특히 산업단지는 수용가의 전기에너지 이용 효율화와 신재생에너지 전원을 활용한 전력거래를 위해 마이크로그리드를 구축하는 추세이다. 본 논문에서는 ESS(Energy Storage System) 복합운영을 통한 비용절감과 전력거래 수익창출 실증을 위하여 나주혁신도시 동수산업단지 내계통과 연계된 제조업체(태산, 범한, 하이옥스)에 구축되는 마이크로그리드 경제성을 분석한다. 경제성 분석 툴인 HOMER를 이용하여 각 업체별 PV(PhotoVoltaic) 및 ESS용량에 따른 순 현재비용과 1[kWh]당 발전단가를 산출한다. 경제성 분석을 위해 각 제조업체의 최근 1년간 부하량과 산업용 전기요금기준, 기업체 소재지의 기후조건에 따른 태양광발전량, 각 기업체 마이크로그리드 실제구축비용을 입력하고, 공인할인율 5.5[%]와 유류비 1500[원/ℓ]를 기준으로 경제성을 분석한다. 분석을 바탕으로 개별 제조업체 부하 특성에 부합한 마이크로그리드 분산전원 및 설비 용량 선정과 운영방안을 제안한다.

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