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Fatty acid incorporation is decreased in astrocytes cultured from α‐synuclein gene‐ablated mice
Author(s) -
Castagnet P. I.,
Golovko M. Y.,
BarcelóCoblijn G. C.,
Nussbaum R. L.,
Murphy E. J.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03247.x
Subject(s) - arachidonic acid , phosphatidylinositol , phospholipid , fatty acid , docosahexaenoic acid , biochemistry , palmitic acid , polyunsaturated fatty acid , biology , cholesteryl ester , chemistry , cholesterol , signal transduction , lipoprotein , enzyme , membrane
Because α‐synuclein may function as a fatty acid binding protein, we measured fatty acid incorporation into astrocytes isolated from wild‐type and α‐synuclein gene‐ablated mice. α‐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, α‐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. α‐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 α‐synuclein‐deficient astrocytes, including decreased 22:6 ( n ‐3) content in the four major phospholipid classes. In summary, these studies demonstrate that α‐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.