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Palmitoylethanolamide stimulation induces allopregnanolone synthesis in C6 cells and primary astrocytes: involvement of peroxisome-proliferator activated receptor-α.
MedLine Citation:
PMID:  21554431     Owner:  NLM     Status:  Publisher    
Palmitoylethanolamide (PEA) regulates many pathophysiological processes in the CNS, including pain perception, convulsions, and neurotoxicity and increasing evidence points to its neuroprotective action. Here, we report that PEA, acting as a ligand of peroxisome-proliferator activated receptor (PPAR)-α, might regulate neurosteroidogenesis in astrocytes, which, as other glial cells and neurons, have the enzymatic machinery for neurosteroid de novo synthesis. For this aim, we used C6 glioma cell line and primary murine astrocytes. In mitochondrial fraction from cells stimulated with PEA, we showed a significant increase in the inactive form of steroidogenic acute regulatory protein (StAR) and of the cytochrome P450 enzyme (P450scc) expression, both proteins considered crucial steps for neurosteroid formation. PEA effects were completely blunted by GW6471, a selective PPAR-α antagonist, or by PPAR-α silencing by RNA interference. Accordingly, allopregnanolone levels were increased in supernatant of PEA-treated astrocytes, as revealed by gas chromatography-mass spectrometry and this effect was inhibited by GW6471. Moreover, PEA showed a protective effect, reducing malondialdehyde formation in cells treated with L-buthionine-(S,R)-sulfoximine, a glutathione depletor, and interestingly PEA effect was partially inhibited by finasteride, a 5α-reductase inhibitor. A similar profile of activity was evidenced by ALLO and the lack of additive effect with PEA suggests that the reduction of oxidative stress by PEA is mediated through ALLO synthesis. This study provides evidence indicating the involvement of the saturated acylethanolamide PEA in ALLO synthesis trough PPAR-α in astrocytes and explores the antioxidative activity of this molecule, confirming its homeostatic and protective role both in physiological and pathological conditions.
Giuseppina Mattace Raso; Emanuela Esposito; Sergio Vitiello; Anna Iacono; Anna Santoro; Giuseppe D'Agostino; Oscar Sasso; Roberto Russo; Pier Vincenzo Piazza; Antonio Calignano; Rosaria Meli
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-7
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  -     ISSN:  1365-2826     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Journal of Neuroendocrinology © 2011 Blackwell Publishing.
Department of Experimental Pharmacology, University of Naples Federico II, Naples, 80131, Italy Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, 98100, Italy INSERM U862, Institut F. Magendie, Université de Bordeaux, Bordeaux, France.
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