Document Detail

The omega-6 fatty acid derivative 15-deoxy-Δ¹²,¹⁴-prostaglandin J2 is involved in neuroprotection by enteric glial cells against oxidative stress.
MedLine Citation:
PMID:  22473776     Owner:  NLM     Status:  MEDLINE    
Increasing evidence suggests that enteric glial cells (EGCs) are critical for enteric neuron survival and functions. In particular, EGCs exert direct neuroprotective effects mediated in part by the release of glutathione. However, other glial factors such as those identified as regulating the intestinal epithelial barrier and in particular the omega-6 fatty acid derivative 15-deoxy-Δ¹²,¹⁴-prostaglandin J2 (15d-PGJ2) could also be involved in EGC-mediated neuroprotection. Therefore, our study aimed to assess the putative role of EGC-derived 15d-PGJ2 in their neuroprotective effects. We first showed that pretreatment of primary cultures of enteric nervous system(ENS)or humann euroblastoma cells (SH-SY5Y)with 15d-PGJ2 dose dependently prevented hydrogen peroxide neurotoxicity. Furthermore, neuroprotective effects of EGCs were significantly inhibited following genetic invalidation in EGCs of the key enzyme involved in 15d-PGJ2 synthesis, i.e. L-PGDS. We next showed that 15d-PGJ2 effects were mediated by an Nrf2 dependent pathway but were not blocked by PPARγ inhibitor (GW9662) in SH-SY5Y cells and enteric neurons. Finally, 15d-PGJ2 induced a significant increase in glutamate cysteine ligase expression and intracellular glutathione in SH cells and enteric neurons. In conclusion, we identified 15d-PGJ2 as a novel glial-derived molecule with neuroprotective effects in the ENS. This study further supports the concept that omega-6 derivatives such as 15d-PGJ2 might be used in preventive and/or therapeutic strategies for the treatment of enteric neuropathies.
Hind Abdo; Maxime M Mahé; Pascal Derkinderen; Kalyane Bach-Ngohou; Michel Neunlist; Bernard Lardeux
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-02
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-07-12     Completed Date:  2012-11-29     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2739-50     Citation Subset:  IM    
INSERM, U913, Nantes, F-44000, France.
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MeSH Terms
Cell Line
Cell Line, Tumor
Cell Survival / drug effects
Cells, Cultured
Glutathione / metabolism
Hydrogen Peroxide / pharmacology
Intramolecular Oxidoreductases / physiology
Lipocalins / physiology
Myenteric Plexus / metabolism*
NF-E2-Related Factor 2 / metabolism
Neuroglia / metabolism*
Oxidative Stress
Phosphopyruvate Hydratase / metabolism
Prostaglandin D2 / analogs & derivatives*,  metabolism
Reg. No./Substance:
0/15-deoxyprostaglandin J2; 0/Lipocalins; 0/NF-E2-Related Factor 2; 0/NFE2L2 protein, human; 41598-07-6/Prostaglandin D2; 70-18-8/Glutathione; 7722-84-1/Hydrogen Peroxide; EC Hydratase; EC 5.3.-/Intramolecular Oxidoreductases; EC R2 D-isomerase
Comment In:
J Physiol. 2012 Jun 15;590(Pt 12):2827   [PMID:  22707588 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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