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 invitro and invivo 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.

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

Graziano, A. C. E.;
2017-01-01

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 invitro and invivo 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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11387/163524
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 26
  • ???jsp.display-item.citation.isi??? 24
social impact