Brain prostaglandin formation is increased by alpha-synuclein gene-ablation during global ischemia.
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.
Golovko
Mikhail Y
MY
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.
Murphy
Eric J
EJ
D000704:Analysis of Variance; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011453:Prostaglandins / Q000145:classification / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods; D051844:alpha-Synuclein / Q000172:deficiency*
D011453:Prostaglandins; D051844:alpha-Synuclein