Enteric glial cells protect neurons from oxidative stress in part via reduced glutathione.
Enteric glial cells (EGCs) are essential in the control of gastrointestinal functions. Although lesions of EGCs are associated with neuronal degeneration in animal models, their direct neuroprotective role remains unknown. Therefore, the aims of this study were to demonstrate the direct neuroprotective effects of EGCs and to identify putative glial mediators involved. First, viral targeted ablation of EGCs in primary cultures of enteric nervous system increased neuronal death both under basal conditions and in the presence of oxidative stress (dopamine, hydrogen peroxide). Second, direct or indirect coculture experiments of EGC lines with primary cultures of enteric nervous system or neuroblastoma cell lines (SH-SY5Y) prevented neurotoxic effects induced by oxidative stress (increased membrane permeability, release of neuronal specific enolase, caspase-3 immunoreactivity, changes in [Ca(2+)](i) response). Finally, combining pharmacological inhibition and mRNA silencing methods, we demonstrated that neuroprotective effects of EGCs were mediated in part by reduced glutathione but not by oxidized glutathione or by S-nitrosoglutathione. Our study identified the neuroprotective effects of EGCs via their release of reduced glutathione, extending their critical role in physiological contexts and in enteric neuropathies.-Abdo, H., Derkinderen, P., Gomes, P., Chevalier, J., Aubert, P., Masson, D., Galmiche, J.-P., Vanden Berghe, P., Neunlist, M., Lardeux, B. Enteric glial cells protect neurons from oxidative stress in part via reduced glutathione.
Abdo
Hind
H
INSERM U913 1, place Alexis Ricordeau, 44093 Nantes, France.
Derkinderen
Pascal
P
Gomes
Priya
P
Chevalier
Julien
J
Aubert
Philippe
P
Masson
Damien
D
Galmiche
Jean-Paul
JP
Vanden Berghe
Pieter
P
Neunlist
Michel
M
Lardeux
Bernard
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D041981:Gastrointestinal Tract / Q000294:innervation / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia; D009474:Neurons / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009419:Nerve Tissue Proteins; D016877:Oxidants; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; C505410:Casp3 protein, rat; D053148:Caspase 3; D010751:Phosphopyruvate Hydratase; D005978:Glutathione; D002118:Calcium; D004298:Dopamine