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Hee-Dae Kim  (Kim HD) 2 Articles
Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo
Jinmi Koo, Han Kyoung Choe, Hee-Dae Kim, Sung Kook Chun, Gi Hoon Son, Kyungjin Kim
Endocrinol Metab. 2015;30(3):361-370.   Published online December 9, 2014
DOI: https://doi.org/10.3803/EnM.2015.30.3.361
  • 4,144 View
  • 37 Download
  • 5 Web of Science
  • 4 Crossref
AbstractAbstract PDFPubReader   
Background

In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions.

Methods

We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system.

Results

Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms.

Conclusion

These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

Citations

Citations to this article as recorded by  
  • High-Throughput Screening Assay for Detecting Drug-Induced Changes in Synchronized Neuronal Oscillations and Potential Seizure Risk Based on Ca2+ Fluorescence Measurements in Human Induced Pluripotent Stem Cell (hiPSC)-Derived Neuronal 2D and 3D Cultures
    Hua-Rong Lu, Manabu Seo, Mohamed Kreir, Tetsuya Tanaka, Rie Yamoto, Cristina Altrocchi, Karel van Ammel, Fetene Tekle, Ly Pham, Xiang Yao, Ard Teisman, David J. Gallacher
    Cells.2023; 12(6): 958.     CrossRef
  • The role of gap junctions in cell death and neuromodulation in the retina
    Gergely Szarka, Márton Balogh, ÁdámJ Tengölics, Alma Ganczer, Béla Völgyi, Tamás Kovács-Öller
    Neural Regeneration Research.2021; 16(10): 1911.     CrossRef
  • Programming effects of maternal stress on the circadian system of adult offspring
    Seongsik Yun, Eun Jeong Lee, Han Kyoung Choe, Gi Hoon Son, Kyungjin Kim, Sooyoung Chung
    Experimental & Molecular Medicine.2020; 52(3): 473.     CrossRef
  • Kisspeptin Neuron-Specific and Self-Sustained Calcium Oscillation in the Hypothalamic Arcuate Nucleus of Neonatal Mice: Regulatory Factors of its Synchronization
    Doyeon Kim, Sangwon Jang, Jeongah Kim, Inah Park, Kyojin Ku, Mijung Choi, Sukwon Lee, Won Do Heo, Gi Hoon Son, Han Kyoung Choe, Kyungjin Kim
    Neuroendocrinology.2020; 110(11-12): 1010.     CrossRef
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Obesity and Metabolism
Effect of Resveratrol, a SIRT1 Activator, on the Interactions of the CLOCK/BMAL1 Complex
Insung Park, Yool Lee, Hee-Dae Kim, Kyungjin Kim
Endocrinol Metab. 2014;29(3):379-387.   Published online September 25, 2014
DOI: https://doi.org/10.3803/EnM.2014.29.3.379
  • 4,194 View
  • 37 Download
  • 25 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   
Background

In mammals, the CLOCK/BMAL1 heterodimer is a key transcription factor complex that drives the cyclic expression of clock-controlled genes involved in various physiological functions and behavioral consequences. Recently, a growing number of studies have reported a molecular link between the circadian clock and metabolism. In the present study, we explored the regulatory effects of SIRTUIN1 (SIRT1), an NAD+-dependent deacetylase, on CLOCK/BMAL1-mediated clock gene expression.

Methods

To investigate the interaction between SIRT1 and CLOCK/BMAL1, we conducted bimolecular fluorescence complementation (BiFC) analyses supplemented with immunocytochemistry assays. BiFC experiments employing deletion-specific mutants of BMAL1 were used to elucidate the specific domains that are necessary for the SIRT1-BMAL1 interaction. Additionally, luciferase reporter assays were used to delineate the effects of SIRT1 on circadian gene expression.

Results

BiFC analysis revealed that SIRT1 interacted with both CLOCK and BMAL1 in most cell nuclei. As revealed by BiFC assays using various BMAL1 deletion mutants, the PAS-B domain of BMAL1 was essential for interaction with SIRT1. Activation of SIRT1 with resveratrol did not exert any significant change on the interaction with the CLOCK/BMAL1 complex. However, promoter analysis using Per1-Luc and Ebox-Luc reporters showed that SIRT1 significantly downregulated both promoter activities. This inhibitory effect was intensified by treatment with resveratrol, indicating a role for SIRT1 and its activator in CLOCK/BMAL1-mediated transcription of clock genes.

Conclusion

These results suggest that SIRT1 may form a regulatory complex with CLOCK/BMAL1 that represses clock gene expression, probably via deacetylase activity.

Citations

Citations to this article as recorded by  
  • Effects of (Poly)phenols on Circadian Clock Gene–Mediated Metabolic Homeostasis in Cultured Mammalian Cells: A Scoping Review
    Noha Sulaimani, Michael J Houghton, Maxine P Bonham, Gary Williamson
    Advances in Nutrition.2024; 15(6): 100232.     CrossRef
  • Synchronization of Fibroblasts Ex Vivo in Psychopharmacology
    Frank Faltraco, Adriana Uzoni, Liliia Shevchuk, Johannes Thome, Denise Palm
    Pharmacopsychiatry.2023; 56(03): 101.     CrossRef
  • Resveratrol as a circadian clock modulator: mechanisms of action and therapeutic applications
    Weronika Spaleniak, Muriel Cuendet
    Molecular Biology Reports.2023; 50(7): 6159.     CrossRef
  • New insights into the mechanisms of diabetic kidney disease: Role of circadian rhythm and Bmal1
    Zhimei Peng, Yanting Liang, Xueying Liu, Jie Shao, Nan Hu, Xinzhou Zhang
    Biomedicine & Pharmacotherapy.2023; 166: 115422.     CrossRef
  • The circadian machinery links metabolic disorders and depression: A review of pathways, proteins and potential pharmacological interventions
    Eleni Pitsillou, Julia Liang, Andrew Hung, Tom C. Karagiannis
    Life Sciences.2021; 265: 118809.     CrossRef
  • Health benefits of dietary chronobiotics: beyond resynchronizing internal clocks
    Jun-qing Huang, Muwen Lu, Chi-Tang Ho
    Food & Function.2021; 12(14): 6136.     CrossRef
  • Dietary Pterostilbene and Resveratrol Modulate the Gut Microbiota Influenced by Circadian Rhythm Dysregulation
    Yen‐Chun Koh, Pei‐Sheng Lee, Yu‐Lun Kuo, Kalyanam Nagabhushanam, Chi‐Tang Ho, Min‐Hsiung Pan
    Molecular Nutrition & Food Research.2021;[Epub]     CrossRef
  • Systems Level Understanding of Circadian Integration with Cell Physiology
    Andrew R. Morris, Daniel L. Stanton, Destino Roman, Andrew C. Liu
    Journal of Molecular Biology.2020; 432(12): 3547.     CrossRef
  • Quercetin, caffeic acid and resveratrol regulate circadian clock genes and aging-related genes in young and old human lung fibroblast cells
    Yoshinori Okada, Mizue Okada
    Molecular Biology Reports.2020; 47(2): 1021.     CrossRef
  • Therapeutic effects of hydro-alcoholic leaf extract of Withania somnifera on age-induced changes in daily rhythms of Sirt1, Nrf2 and Rev-erbα in the SCN of male Wistar rats
    Kowshik Kukkemane, Anita Jagota
    Biogerontology.2020; 21(5): 593.     CrossRef
  • Pharmacological basis and new insights of resveratrol action in the cardiovascular system
    Chak Kwong Cheng, Jiang‐Yun Luo, Chi Wai Lau, Zhen‐Yu Chen, Xiao Yu Tian, Yu Huang
    British Journal of Pharmacology.2020; 177(6): 1258.     CrossRef
  • Effects of resveratrol on the levels of ATP, 5-HT and GAP-43 in the hippocampus of mice exposed to chronic unpredictable mild stress
    Ji-Duo Shen, Yue-Wen Zhang, Bao-Ying Wang, Li Bai, Shuai-Fei Lu, Lei-Lei Zhu, Ming Bai, Yu-Cheng Li, Er-Ping Xu
    Neuroscience Letters.2020; 735: 135232.     CrossRef
  • Resveratrol and Vascular Function
    Huige Li, Ning Xia, Solveig Hasselwander, Andreas Daiber
    International Journal of Molecular Sciences.2019; 20(9): 2155.     CrossRef
  • Sirt1 Promotes Osteogenic Differentiation and Increases Alveolar Bone Mass via Bmi1 Activation in Mice
    Hua Wang, Zixuan Hu, Jun Wu, Yukun Mei, Qian Zhang, Hengwei Zhang, Dengshun Miao, Wen Sun
    Journal of Bone and Mineral Research.2019; 34(6): 1169.     CrossRef
  • RNA-Sequencing Analysis Reveals l-Theanine Regulating Transcriptional Rhythm Alteration in Vascular Smooth Muscle Cells Induced by Dexamethasone
    Ruru Wang, Menchao Xiao, Yujing Zhang, Chi-Tang Ho, Xiaochun Wan, Daxiang Li, Zhongwen Xie
    Journal of Agricultural and Food Chemistry.2019; 67(19): 5413.     CrossRef
  • The effects of phytochemicals on circadian rhythm and related diseases
    Tao Xu, Baiyi Lu
    Critical Reviews in Food Science and Nutrition.2019; 59(6): 882.     CrossRef
  • Effect of piceatannol on circadian Per2 expression in vitro and in vivo
    Takayuki Yamamoto, Shiho Iwami, Shinya Aoyama, Hiroko Maruki-Uchida, Sadao Mori, Rina Hirooka, Kengo Takahashi, Minoru Morita, Shigenobu Shibata
    Journal of Functional Foods.2019; 56: 49.     CrossRef
  • AMPK/SIRT1/p38 MAPK signaling pathway regulates alcohol‑induced neurodegeneration by resveratrol
    Xinyi Gu, Zhengxu Cai, Ming Cai, Kun Liu, Dan Liu, Qinsong Zhang, Jing Tan, Qiang Ma
    Molecular Medicine Reports.2018;[Epub]     CrossRef
  • Effects of fluctuating temperature and food availability on reproduction and lifespan
    Tonia S. Schwartz, Phillip Pearson, John Dawson, David B. Allison, Julia M. Gohlke
    Experimental Gerontology.2016; 86: 62.     CrossRef
  • Multiple Integrated Complementary Healing Approaches: Energetics & Light for bone
    Michael G. Gray, Brett R. Lackey, Evelyn F. Patrick, Sandra L. Gray, Susan G. Hurley
    Medical Hypotheses.2016; 86: 18.     CrossRef
  • Effects of BMAL1–SIRT1-positive cycle on estrogen synthesis in human ovarian granulosa cells: an implicative role of BMAL1 in PCOS
    Jiaou Zhang, Jiansheng Liu, Kai Zhu, Yan Hong, Yun Sun, Xiaoming Zhao, Yanzhi Du, Zi-Jiang Chen
    Endocrine.2016; 53(2): 574.     CrossRef
  • Articles in 'Endocrinology and Metabolism' in 2014
    Won-Young Lee
    Endocrinology and Metabolism.2015; 30(1): 47.     CrossRef
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