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J Cell Mol Med. 2017 Oct;21(10):2563-2572. doi: 10.1111/jcmm.13177. Epub 2017 May 9.

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

Author information

1
Department of Biomedical and Biotechnological Sciences, Physiology Section, University of Catania, Catania, Italy.
2
Department of Drug Sciences, University of Catania, Catania, Italy.
3
IOM Ricerca, Viagrande, Italy.
4
Institute Neurological Sciences, National Research Council, Catania, Italy.

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.

KEYWORDS:

connexin 43; gap junctions; growth factors; neuroprotection; olfactory glia

PMID:
28488330
PMCID:
PMC5618696
DOI:
10.1111/jcmm.13177
[Indexed for MEDLINE]
Free PMC Article

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