Fatty acid incorporation is decreased in astrocytes cultured from alpha-synuclein gene-ablated mice.
Because alpha-synuclein may function as a fatty acid binding protein, we measured fatty acid incorporation into astrocytes isolated from wild-type and alpha-synuclein gene-ablated mice. alpha-Synuclein deficiency decreased palmitic acid (16:0) incorporation 31% and arachidonic acid [20:4 (n-6)] incorporation 39%, whereas 22:6 (n-3) incorporation was unaffected. In neutral lipids, fatty acid targeting of 20:4 (n-6) and 22:6 (n-3) (docosahexaenoic acid) to the neutral lipid fraction was increased 1.7-fold and 1.6-fold, respectively, with an increase in each of the major neutral lipids. This was consistent with a 3.4- to 3.8-fold increase in cholesteryl ester and triacylglycerol mass. In the phospholipid fraction, alpha-synuclein deficiency decreased 16:0 esterification 39% and 20:4 (n-6) esterification 43% and decreased the distribution of these fatty acids, including 22:6 (n-3), into this lipid pool. alpha-Synuclein gene-ablation significantly decreased the trafficking of these fatty acids to phosphatidylinositol. This observation is consistent with changes in phospholipid fatty acid composition in the alpha-synuclein-deficient astrocytes, including decreased 22:6 (n-3) content in the four major phospholipid classes. In summary, these studies demonstrate that alpha-synuclein deficiency significantly disrupted astrocyte fatty acid uptake and trafficking, with a marked increase in fatty acid trafficking to cholesteryl esters and triacylglycerols and decreased trafficking to phospholipids, including phosphatidylinositol.
Castagnet
P I
PI
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota, Grand Forks, North Dakota 58202-9037, USA.
Golovko
M Y
MY
Barceló-Coblijn
G C
GC
Nussbaum
R L
RL
Murphy
E J
EJ
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002788:Cholesterol Esters / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004951:Esterification; D005227:Fatty Acids / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D051843:Synucleins; D051844:alpha-Synuclein
D002788:Cholesterol Esters; D005227:Fatty Acids; D009419:Nerve Tissue Proteins; D010743:Phospholipids; C497605:Snca protein, mouse; D051843:Synucleins; D051844:alpha-Synuclein