PMID- 17250657
OWN - NLM
STAT- MEDLINE
DCOM- 20070529
LR  - 20200128
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 101
IP  - 1
DP  - 2007 Apr
TI  - Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and 
      turnover in brain phospholipids.
PG  - 201-11
AB  - Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces 
      arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an 
      endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca 
      ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown. In the present 
      study, we examined the effect of Snca gene ablation on brain 22:6n-3 metabolism. 
      We determined 22:6n-3 uptake and incorporation into brain phospholipids by 
      infusing awake, wild-type and Snca-/- mice with [1-14C]22:6n-3 using steady-state 
      kinetic modeling. In addition, because Snca modulates 20:4n-6-CoA formation, we 
      assessed microsomal Acsl activity using 22:6n-3 as a substrate. Although Snca 
      gene ablation does not affect brain 22:6n-3 uptake, brain 22:6n-3-CoA mass was 
      elevated 1.5-fold in the absence of Snca. This is consistent with the 1.6- to 
      2.2-fold increase in the incorporation rate and turnover in ethanolamine 
      glycerophospholipid, phosphatidylserine, and phosphatidylinositol pools. 
      Increased 22:6n-3-CoA mass was not the result of altered Acsl activity, which was 
      unaffected by the absence of Snca. While Snca bound 22:6n-3, Kd = 1.0 +/- 0.5 
      micromol/L, it did not bind 22:6n-3-CoA. These effects of Snca gene deletion on 
      22:6n-3 brain metabolism are opposite to what we reported previously for brain 
      20:4n-6 metabolism and are likely compensatory for the decreased 20:4n-6 
      metabolism in brains of Snca-/- mice.
FAU - Golovko, Mikhail Y
AU  - Golovko MY
AD  - Department of Pharmacology, Physiology, and Therapeutics, University of North 
      Dakota, Grand Forks, North Dakota 58202-9037, USA.
FAU - Rosenberger, Thad A
AU  - Rosenberger TA
FAU - Feddersen, Soren
AU  - Feddersen S
FAU - Faergeman, Nils J
AU  - Faergeman NJ
FAU - Murphy, Eric J
AU  - Murphy EJ
LA  - eng
GR  - 1P20 RR17699-01/RR/NCRR NIH HHS/United States
GR  - 1R21-NS043697-01A/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070122
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Phospholipids)
RN  - 0 (alpha-Synuclein)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.3 (Acsl1 protein, rat)
SB  - IM
MH  - Animals
MH  - Brain/*metabolism/physiopathology
MH  - Brain Chemistry/*genetics
MH  - Carbon Radioisotopes
MH  - Coenzyme A Ligases/metabolism
MH  - Docosahexaenoic Acids/*metabolism
MH  - Kinetics
MH  - Lipid Metabolism/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Phospholipids/*metabolism
MH  - Protein Binding/genetics
MH  - Up-Regulation/genetics
MH  - alpha-Synuclein/*genetics
EDAT- 2007/01/26 09:00
MHDA- 2007/05/30 09:00
CRDT- 2007/01/26 09:00
PHST- 2007/01/26 09:00 [pubmed]
PHST- 2007/05/30 09:00 [medline]
PHST- 2007/01/26 09:00 [entrez]
AID - JNC4357 [pii]
AID - 10.1111/j.1471-4159.2006.04357.x [doi]
PST - ppublish
SO  - J Neurochem. 2007 Apr;101(1):201-11. doi: 10.1111/j.1471-4159.2006.04357.x. Epub 
      2007 Jan 22.