Vitamins E and C do not effectively inhibit low density lipoprotein oxidation by ferritin at lysosomal pH

Ojo, O. O. and Leake, D. S. ORCID: https://orcid.org/0000-0002-1742-6134 (2021) Vitamins E and C do not effectively inhibit low density lipoprotein oxidation by ferritin at lysosomal pH. Free Radical Research, 55 (5). pp. 525-534. ISSN 1071-5762 doi: 10.1080/10715762.2021.1964494

Abstract/Summary

Low density lipoprotein (LDL) might be oxidised by iron in the lysosomes of macrophages in atherosclerotic lesions. We have shown previously that the iron-storage protein ferritin can oxidise LDL at lysosomal pH. We have now investigated the roles of the most important antioxidant contained in LDL, α-tocopherol (the main form of vitamin E) and of ascorbate (vitamin C), a major water-soluble antioxidant, on LDL oxidation by ferritin at lysosomal pH (pH 4.5). We incubated LDL with ferritin at pH 4.5 and 37 oC and measured its oxidation by monitoring the formation of conjugated dienes at 234 nm in a spectrophotometer. α-Tocopherol is well known to inhibit LDL oxidation at pH 7.4, but enrichment of LDL with α-tocopherol was unable to inhibit LDL oxidation by ferritin at pH 4.5. Ascorbate had a complex effect on LDL oxidation by ferritin at lysosomal pH and exhibited both antioxidant and pro-oxidant effects. It had no antioxidant effect on partially oxidised LDL, only a pro-oxidant effect. Ascorbate completely inhibited LDL oxidation by copper at pH 7.4 for a long period, but in marked contrast did not inhibit LDL oxidation by copper at lysosomal pH. Dehydroascorbate, the oxidation product of ascorbate, had a pronounced pro-oxidant effect on LDL incubated with ferritin at pH 4.5. The inability of α-tocopherol and ascorbate to effectively inhibit LDL oxidation by ferritin at lysosomal pH might help to explain why the large clinical trials with these vitamins failed to show protection against cardiovascular diseases.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/99640
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Taylor and Francis
Download/View statistics	View download statistics for this item