Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Tenovin-1 Induces Senescence and Decreases Wound-Healing Activity in Cultured Rat Primary Astrocytes

  • Bang, Minji (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University) ;
  • Ryu, Onjeon (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University) ;
  • Kim, Do Gyeong (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University) ;
  • Mabunga, Darine Froy (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University) ;
  • Cho, Kyu Suk (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University) ;
  • Kim, Yujeong (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University) ;
  • Han, Seol-Heui (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University) ;
  • Kwon, Kyoung Ja (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University) ;
  • Shin, Chan Young (Department of Neuroscience, School of Medicine and Center for Neuroscience Research, Konkuk University)
  • Received : 2018.06.05
  • Accepted : 2018.07.03
  • Published : 2019.05.01
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Abstract

Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence- associated ${\beta}$-galactosidase (SA-${\beta}$-gal) activity. Tenovin-1-treated astrocytes showed increased SA-${\beta}$-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-$1{\beta}$, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.

Keywords

References

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