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Journal of Lipid Research, Vol. 42, 1368-1376, September 2001
Copyright © 2001 by Lipid Research, Inc.


Original Article

Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes

Deborah E. Williarda, Shawn D. Harmona, Terry L. Kaducea, Meredith Preussd, Steven A. Mooreb, Michael E. C. Robbinsd, and Arthur A. Spectora,c
a Departments of Biochemistry, College of Medicine, University of Iowa, Iowa City, IA 52242
b Pathology, College of Medicine, University of Iowa, Iowa City, IA 52242
c Internal Medicine, College of Medicine, University of Iowa, Iowa City, IA 52242
d Free Radical and Radiation Biology Program, College of Medicine, University of Iowa, Iowa City, IA 52242

Correspondence to: Arthur A. Spector, at the Department of Biochemistry, 4-403 BSB, University of Iowa, Iowa City, IA 52242., arthur-spector{at}uiowa.edu (E-mail)

DHA, the main n-3 PUFA in the brain, is synthesized from n-3 PUFA precursors by astrocytes. To assess the potential of this process to supply DHA for the brain, we investigated whether the synthesis in astrocytes is dependent on DHA availability. Rat brain astrocytes differentiated with dibutyryl cAMP and incubated in media containing 10% fetal bovine serum synthesized DHA from {alpha}-linolenic acid ([1-14C]18:3n-3), docosapentaenoic acid ([3-14C]22:5n-3), tetracosapentaenoic acid ([3-14C]24:5n-3), and tetracosahexaenoic acid ([3-14C]24:6n-3). When DHA was added to media containing a 5 µM concentration of these 14C-labeled n-3 PUFA, radiolabeled DHA synthesis was reduced but not completely suppressed even when the DHA concentration was increased to 15 µM. Radiolabeled DHA synthesis also was reduced but not completely suppressed when the astrocytes were treated with 30 µM DHA for 24 h before incubation with 5 µM [1-14C]18:3n-3.

These findings indicate that although the DHA synthesis in astrocytes is dependent on DHA availability, some synthesis continues even when the cells have access to substantial amounts of DHA. This suggests that DHA synthesis from n-3 PUFA precursors is a constitutive process in the brain and, therefore, is likely to have an essential function. — Williard, D. E., S. D. Harmon, T. L. Kaduce, M. Preuss, S. A. Moore, M. E. C. Robbins, and A. A. Spector. Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes. J. Lipid Res. 2001. 42: 1368;–1376.

Supplementary key words: {alpha}-linolenic acid, docosapentaenoic acid, tetracosapentaenoic acid, tetracosahexaenoic acid, cAMP, elongation, desaturation, retroconversion


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