Open AccessInhibition of Cx43 mediates protective effects on hypoxic/reoxygenated human neuroblastoma cells
Author(s) -
Vicario Nunzio,
Calabrese Giovanna,
Zappalà Agata,
Parenti Carmela,
Forte Stefano,
Graziano Adriana Carol Eleonora,
Vanella Luca,
Pellitteri Rosalia,
Cardile Venera,
Parenti Rosalba
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13177
Subject(s) - neuroprotection , gap junction , carbenoxolone , connexin , microbiology and biotechnology , sh sy5y , viability assay , biology , cell culture , pharmacology , neuroscience , chemistry , intracellular , neuroblastoma , genetics
Olfactory ensheathing cells ( OEC s), 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 ‐ SY 5Y 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 ( GJ s) and Cx43‐hemichannels ( HC s) 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 ‐ SY 5Y and allow to these cultures to overcome the injury. Our findings support the hypothesis that both OEC ‐ CM and the inhibition of Cx43‐ GJ s and Cx43‐ HC s offer a neuroprotective effect by reducing Cx43‐mediated cell‐to‐cell and cell‐to‐extracellular environment communications.