Document Detail

Brain prostaglandin formation is increased by alpha-synuclein gene-ablation during global ischemia.
MedLine Citation:
PMID:  18226447     Owner:  NLM     Status:  MEDLINE    
We have previously demonstrated that alpha-synuclein (Snca) gene ablation reduces brain arachidonic acid (20:4n-6) turnover rate in phospholipids through modulation of endoplasmic reticulum-localized acyl-CoA synthetase activity. Although 20:4n-6 is a precursor for prostaglandin (PG), Snca effect on PG levels is unknown. In the present study, we examined the effect of Snca ablation on brain PG level at basal conditions and following 30s of global ischemia. Brain PG were extracted with methanol, purified on C(18) cartridges, and analyzed by LC-MS/MS. We demonstrate, for the first time, that Snca gene ablation did not affect brain PG mass under normal physiological conditions. However, total PG mass and masses of individual PG were elevated approximately 2-fold upon global ischemia in the absence of Snca. These data are consistent with our previously observed reduction in 20:4n-6 recycling through endoplasmic reticulum-localized acyl-CoA synthetase in the absence of Snca, which may result in the increased 20:4n-6 availability for PG production in the absence of Snca during global ischemia and suggest a role for Snca in brain inflammatory response.
Mikhail Y Golovko; Eric J Murphy
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-12-23
Journal Detail:
Title:  Neuroscience letters     Volume:  432     ISSN:  0304-3940     ISO Abbreviation:  Neurosci. Lett.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-18     Completed Date:  2008-06-12     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  7600130     Medline TA:  Neurosci Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  243-7     Citation Subset:  IM    
Department of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND 58202-9037, USA.
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MeSH Terms
Analysis of Variance
Chromatography, Liquid / methods
Gene Expression Regulation / physiology
Ischemia / metabolism*,  pathology,  physiopathology
Mice, Knockout
Prostaglandins / classification,  metabolism*
Tandem Mass Spectrometry / methods
alpha-Synuclein / deficiency*
Grant Support
P20 RR 17699/RR/NCRR NIH HHS; P20 RR017699-010004/RR/NCRR NIH HHS
Reg. No./Substance:
0/Prostaglandins; 0/alpha-Synuclein

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