Inhibition of Cx43 mediates protective effects on hypoxic/reoxygenated human neuroblastoma cells.

Abstract

Olfactory ensheathing cells (OECs), a special population of glial cells, are able to synthesise several trophic factors exerting a neuroprotective action and promoting growth and functional recovery in both in vitro and in vivo models. In the present work, we investigated the neuroprotective effects of OEC-conditioned medium (OEC-CM) on two different human neuron-like cell lines, SH-SY5Y and SK-N-SH (neuroblastoma cell lines), under normoxic and hypoxic conditions. In addition, we also focused our attention on the role of connexins (Cxs) in the neuroprotective processes. Our results confirmed OEC-CM mediated neuroprotection as shown by cell adherence, proliferation and cellular viability analyses. Reduced connexin 43 (Cx43) levels in OEC-CM compared to unconditioned cells in hypoxic conditions prompted us to investigate the role of Cx43-Gap junctions (GJs) and Cx43-hemichannels (HCs) in hypoxic/reoxygenation injury using carbenoxolone (non-selective GJ inhibitor), ioxynil octanoato (selective Cx43-GJ inhibitor) and Gap19 (selective Cx43-HC inhibitor). We found that Cx43-GJ and Cx43-HC inhibitors are able to protect SH-SY5Y and allow to these cultures to overcome the injury. Our findings support the hypothesis that both OEC-CM and the inhibition of Cx43-GJs and Cx43-HCs offer a neuroprotective effect by reducing Cx43-mediated cell-to-cell and cell-to-extracellular environment communications.

• Authors: Nunzio Vicario, Giovanna Calabrese, Agata Zappalà, Carmela Parenti, Stefano Forte, Adriana Carol Eleonora Graziano, Luca Vanella, Rosalia Pellitteri, Venera Cardile, Rosalba Parenti
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 21 Issue 10 Pg. 2563-2572 (10 2017) ISSN: 1582-4934 [Electronic] England
• PMID: 28488330 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• Connexin 43
• Culture Media, Conditioned
• Neuroprotective Agents
• Peptide Fragments
• Oxygen

Topics

• Animals
• Animals, Newborn
• Cell Adhesion (drug effects)
• Cell Hypoxia
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Connexin 43 (antagonists & inhibitors, chemistry, metabolism)
• Culture Media, Conditioned (pharmacology)
• Gap Junctions (drug effects, metabolism)
• Humans
• Mice
• Neuroblastoma (metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Olfactory Bulb (cytology, metabolism)
• Oxygen (metabolism)
• Peptide Fragments (pharmacology)