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Threshold protective effect of deuterated polyunsaturated fatty acids on peroxidation of lipid bilayers.
- Source :
-
The FEBS journal [FEBS J] 2019 Jun; Vol. 286 (11), pp. 2099-2117. Date of Electronic Publication: 2019 Mar 22. - Publication Year :
- 2019
-
Abstract
- Autoxidation of polyunsaturated fatty acids (PUFAs) damages lipid membranes and generates numerous toxic by-products implicated in neurodegeneration, aging, and other pathologies. Abstraction of bis-allylic hydrogen atoms is the rate-limiting step of PUFA autoxidation, which is inhibited by replacing bis-allylic hydrogens with deuterium atoms (D-PUFAs). In cells, the presence of a relatively small fraction of D-PUFAs among natural PUFAs is sufficient to effectively inhibit lipid peroxidation (LPO). Here, we investigate the effect of various D-PUFAs on the stability of liposomes under oxidative stress conditions. The permeability of vesicle membranes to fluorescent dyes was measured as a proxy for bilayer integrity, and the formation of conjugated dienes was monitored as a proxy for LPO. Remarkably, both approaches reveal a similar threshold for the protective effect of D-PUFAs in liposomes. We show that protection rendered by D-PUFAs depends on the structure of the deuterated fatty acid. Our findings suggest that protection of PUFAs against autoxidation depends on the total level of deuterated bi-sallylic (CD <subscript>2</subscript> ) groups present in the lipid bilayer. However, the phospholipid containing 6,6,9,9,12,12,15,15,18,18-d <subscript>10</subscript> -docosahexaenoic acid exerts a stronger protective effect than should be expected from its deuteration level. These findings further support the application of D-PUFAs as preventive/therapeutic agents in numerous pathologies that involve LPO.<br /> (© 2019 Federation of European Biochemical Societies.)
- Subjects :
- Computer Simulation
Drug Delivery Systems
Drug Evaluation, Preclinical
Fatty Acids, Unsaturated chemistry
Lipid Peroxidation drug effects
Liposomes
Models, Chemical
Molecular Structure
Monte Carlo Method
Oxidative Stress drug effects
Phospholipids chemical synthesis
Phospholipids metabolism
Structure-Activity Relationship
Antioxidants pharmacology
Deuterium chemistry
Fatty Acids, Unsaturated pharmacology
Lipid Bilayers metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1742-4658
- Volume :
- 286
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The FEBS journal
- Publication Type :
- Academic Journal
- Accession number :
- 30851224
- Full Text :
- https://doi.org/10.1111/febs.14807