Effect of Docosahexaenoic Acid on the Synthesis of Phosphatidylserine in Rat Brain Microsomes and C6 Glioma Cells

• Published in: Journal of neurochemistry 1998-01, Vol.70 (1), p.24-30
• Main Authors: Garcia, Martha C., Ward, Glenn, Ma, Yee‐Chung, Salem, Norman, Kim, Hee‐Yong
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry and metabolism; Biological and medical sciences; Brain; Brain - metabolism; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; C6 glioma cells; Central nervous system; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; Electrospray mass spectrometry; Female; Fundamental and applied biological sciences. Psychology; Glioma - metabolism; Glioma - pathology; Microsomes; Microsomes - metabolism; n‐3 deficiency; Phosphatidylserine; Phosphatidylserines - biosynthesis; Rats; Rats, Sprague-Dawley; Serine - metabolism; Serine base exchange; Tumor Cells, Cultured; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.70010024.x

: Docosahexaenoic acid (22:6n‐3) is the major polyunsaturated fatty acid (PUFA) in the CNS and accumulates particularly in phosphatidylserine (PS). We have investigated the effect of the 22:6n‐3 compositional status on the synthesis of PS. The fatty acid composition of brain microsomes from offspring of rats artificially reared on an n‐3‐deficient diet showed a dramatic reduction of 22:6n‐3 content (1.7 ± 0.1%) when compared with control animals (15.0 ± 0.2%). The decrease was accompanied by an increase in docosapentaenoic acid (22:5n‐6) content, which replaced the 22:6n‐3 phospholipids with 22:5n‐6 molecular species, as demonstrated using HPLC/electrospray mass spectrometry. The n‐3 deficiency did not affect the total amount of polyunsaturated phospholipids in brain microsomes; however, it was associated with a decrease in the total polyunsaturated PS content and with increased levels of 1‐stearoyl‐2‐docosapentanoyl (18:0/22:5n‐6) species, particularly in phosphatidylcholine. Incorporation of [3H]serine into PS in rat brain microsomes from n‐3‐deficient animals was slightly but significantly less than that of the control animals. Similarly, C6 glioma cells cultured for 24 h in 22:6n‐3‐supplemented media (10–40 µM) showed a significant increase in the synthesis of [3H]PS when compared with unsupplemented cells. Our data show that neuronal and glial PS synthesis is sensitive to changes in the docosahexaenoate levels of phospholipids and suggest that 22:6n‐3 may be a modulator of PS synthesis.