Abstract
Previously, this laboratory reported the isolation of variants, RAW.12 and RAW.108, from the macrophage-like cell line RAW 264.7 that are defective in plasmalogen biosynthesis [Zoeller, R.A. et al. 1992. J. Biol. Chem. 267: 8299–8306]. Fatty acid analysis showed significant changes in the mutants in the ethanolamine phospholipids (PE), the only phospholipid class in which the plasmalogen species, plasmenylethanolamine, contributes significantly. Within the PE fraction, docosapentaenoic (DPA; 22:5n–3) and docosahexaenoic (DHA; 22:6n–3) acids were reduced by approximately 50% in the variants while the levels of arachidonic acid (AA; 20:4n–6) remained unaffected. The decrease in DHA was accompanied by a 50% decrease in labeling PE with [3H]DHA over a 90-min period. Restoration of plasmenylethanolamine by supplementing the growth medium with sn-1-hexadecylglycerol (HG) completely reversed these changes in RAW.108. Pre-existing pools of plasmenylethanolamine were not required for restoration of normal [3H]DHA labeling; addition of HG only during the labeling period was sufficient. Due to the loss of Δ1′-desaturase in RAW.12, HG supplementation resulted in the accumulation of plasmenylethanolamine's immediate biosynthetic precursor, plasmanylethanolamine. Even though this latter phospholipid contained only the ether functionality (lacking the vinyl ether double bond) it was sufficient to restore wild type-like fatty acid composition and DHA labeling of the ethanolamine phospholipids, identifying the ether bond as a structural determinant for this specificity. In summary, we have used these mutants to establish that the plasmalogen status of a cell can influence the levels of certain polyunsaturated fatty acids. These results support the notion that certain polyunsaturated fatty acids, such as DHA, can be selectively targeted to plasmalogens and that this targeting occurs during de novo biosynthesis, or shortly thereafter, through modification of nascent plasmalogen pools. —Gaposchkin, D. P., and R. A. Zoeller. Plasmalogen status influences docosahexaenoic acid levels in a macrophage cell line: insights using ether lipid-deficient variants. J. Lipid Res. 1999. 40: 495–503.
Highlights
This laboratory reported the isolation of variants, RAW.12 and RAW.108, from the macrophagelike cell line RAW 264.7 that are defective in plasmalogen biosynthesis [Zoeller, R.A. et al 1992
Like plasmenylethanolamine or plasmenylcholine, that bears a vinyl ether at the sn-1 position of the glycerol backbone is classified as a “plasmalogen.” Putative functions for plasmalogens include regulation of certain PKC isozymes [4, 5], their possible role in membrane–membrane fusion events [6], and the ability to serve as endogenous antioxidants [7]
The cells likely compensated for the loss of plasmenylethanolamine biosynthesis by increasing phosphatidylethanolamine synthesis, as observed in other ether lipid-deficient variants [32,33,34]
Summary
This laboratory reported the isolation of variants, RAW. and RAW.108, from the macrophagelike cell line RAW 264.7 that are defective in plasmalogen biosynthesis [Zoeller, R.A. et al 1992. Due to the loss of ⌬1desaturase in RAW., HG supplementation resulted in the accumulation of plasmenylethanolamine’s immediate biosynthetic precursor, plasmanylethanolamine Even though this latter phospholipid contained only the ether functionality (lacking the vinyl ether double bond) it was sufficient to restore wild type-like fatty acid composition and DHA labeling of the ethanolamine phospholipids, identifying the ether bond as a structural determinant for this specificity. We have used these mutants to establish that the plasmalogen status of a cell can influence the levels of certain polyunsaturated fatty acids. Plasmalogen status influences docosahexaenoic acid levels in a macrophage cell line: insights using ether lipid-deficient variants. Studies of patients with inborn errors of plasmalogen biosynthesis revealed decreased levels of DHA in several tissues [23,24,25] This has been attributed to the loss of peroxisomal functions which is associated with these patients
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
