Chemical hypoxia in human pluripotent NT2 stem cell-derived neurons: Effect of hydroxamic acid and benzamide-based epigenetic drugs

  • Rushita A Bagchi Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
  • Ashim K Bagchi Institute of Cardiovascular Sciences, St. Boniface Albrechtsen Research Centre, Winnipeg, Manitoba, Canada.
  • Ankita Salunke Department of Zoology, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
  • Dipak K Hens Sonamukhi College, The University of Burdwan, West Bengal, India.
  • Pragna H Parikh Department of Zoology, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India.
Keywords: pluripotent, neuron, hypoxia, histone deacetylase, gene expression

Abstract

Hypoxia-induced oxidative stress contributes to neuronal damage leading to many neurodegenerative disorders. Hypoxia promotes many downstream effectors such as hypoxia-inducible factor-1α (HIF-1α) in order to restore respiratory homeostasis due to low oxygen availability and increased ROS. Use of histone deacetylase (HDAC) inhibitors may modulate hypoxia-induced neuronal cell damage.  In this study, we used two chemically diverse HDAC inhibitors to investigate their effect on hypoxia-exposed neuronal cells. Human pluripotent NT-2 stem cell-derived neuronal differentiated cells were exposed to CoCl2 pre-treatment for 6h to induce hypoxia, prior to supplementation of HDAC inhibitor (SAHA or MGCD0103). Treatment with HDAC inhibitor improved cell viability in hypoxia-induced neuronal cells. The increased HIF1α expression in hypoxia-induced neuronal cells was blunted by these HDAC inhibitors with a concomitant decrease in ROS production. CoCl2 treatment caused an increase in IL-1β, which was significantly inhibited by these HDAC inhibitors. Furthermore, apoptosis induced in these CoCl2 treated neuronal cells was mitigated by SAHA as well MGCD0103 suggesting that these HDAC inhibitors are capable of reducing cellular toxicity, inflammation and apoptosis, and thus, could be beneficial as therapeutic molecules for many neuropathological conditions.

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Published
2019-08-22
How to Cite
Bagchi, R. A., Bagchi, A. K., Salunke, A., Hens, D. K. and Parikh, P. H. (2019) “Chemical hypoxia in human pluripotent NT2 stem cell-derived neurons: Effect of hydroxamic acid and benzamide-based epigenetic drugs”, Neuroscience Research Notes, 2(3), pp. 12-19. doi: 10.31117/neuroscirn.v2i3.30.
Section
Research Notes