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Reduced docosahexaenoic acid metabolism and concentration in brain phospholipids of calcium‐independent phospholipase A2 VIA (iPLA2β) ‐ knockout mice
Author(s) -
Cheon Yewon,
Kim HyungWook,
Igarashi Miki,
Modi Hiren R,
Chang Lisa,
Ma Kaizong,
Greenstein Deanna,
Wohltmann Mary,
Turk John,
Rapoport Stanley I,
Taha Ameer M
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.585.4
Calcium independent phospholipase A2 type VIA (iPLA2β) has been shown to release docosahexaenoic acid (DHA) from phospholipids in vitro. Mutations of this enzyme have been associated with dystonia‐Parkinson's and infantile neuroaxonal dystrophy. To understand its biochemical and functional role in brain, we applied our in vivo kinetic method using radiolabeled DHA in 4–5 momths old wildtype (iPLA2β+/+) and knockout (iPLA2β−/−) mice, to measure DHA turnover and incorporation in brain phospholipids, fatty acid concentrations and enzyme expression of phospholipases (PLAs) and cyclooxygenases (COXs). DHA turnover did not differ significantly between wildtype and knockout mice, iPLA2β −/− mice showed decreased DHA incorporation from plasma into brain phospholipids, reduced concentrations of several fatty acids (including DHA) in brain ethanolamine glycerophospholipid and phosphatidylserine and increased fatty acid concentrations in lysophospholipids. Cytosolic PLA2 IVA mRNA and secretory IIA PLA2 mRNA, protein and activity were increased, whereas iPLA2γ mRNA expression was decreased in iPLA2β −/− mice. COX‐2 protein was increased, whereas COX‐1 was decreased. Our results suggest a role of the iPLA2β gene in brain fatty acid metabolism and enzyme markers of inflammation, which may be relevant to human carriers of a similar mutation. This work was supported by the Intramural Research Program of the NIA.