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Sung Kook Chun  (Chun SK) 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
  • 4,450 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

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  • 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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Sumoylation of Hes6 Regulates Protein Degradation and Hes1-Mediated Transcription
Jiwon Lee, Sung Kook Chun, Gi Hoon Son, Kyungjin Kim
Endocrinol Metab. 2015;30(3):381-388.   Published online May 18, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.3.381
  • 4,020 View
  • 38 Download
  • 2 Web of Science
  • 1 Crossref
AbstractAbstract PDFPubReader   
Background

Hes6 is a transcriptional regulator that induces transcriptional activation by binding to transcription repressor Hes1 and suppressing its activity. Hes6 is controlled by the ubiquitin-proteosome-mediated degradation system. Here we investigated the sumoylation of Hes6 and its functional role in its rhythmic expression.

Methods

Hes6, SUMO, and ubiquitin were transfected into HeLa cells and the expression pattern was observed by Western blot and immunoprecipitation. To confirm the effect of sumoylation on the rhythmic expression of Hes6, we generated mouse Hes6 promoter-driven GFP-Hes6 fusion constructs and expressed these constructs in NIH 3T3 cells.

Results

Overexpression of SUMO led to sumoylation of Hes6 at both lysine 27 and 30. Protein stability of Hes6 was decreased by sumoylation. Moreover, expression of a Hes6 sumoylation-defective mutant, the 2KR (K27/30R) mutant, or co-expression of SUMO protease SUSP1 with native Hes6, strongly reduced ubiquitination. In addition, sumoylation was associated with both the rhythmic expression and transcriptional regulation of Hes6. Wild type Hes6 showed oscillatory expression with about 2-hour periodicity, whereas the 2KR mutant displayed a longer period. Furthermore, sumoylation of Hes6 derepressed Hes1-induced transcriptional repression.

Conclusion

Hes6 sumoylation plays an important role in the regulation of its stability and Hes1-mediated transcription. These results suggest that sumoylation may be crucial for rhythmic expression of Hes6 and downstream target genes.

Citations

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  • Identification of genes with oscillatory expression in glioblastoma: the paradigm of SOX2
    Richard Zhiming Fu, Oliver Cottrell, Luisa Cutillo, Andrew Rowntree, Zsolt Zador, Heiko Wurdak, Nancy Papalopulu, Elli Marinopoulou
    Scientific Reports.2024;[Epub]     CrossRef
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