Surprising inability of singlet oxygen-generated 6-hydroperoxycholesterol to induce damaging free radical lipid peroxidation in cell membranes. Photochem Photobiol 2010;86(4):747-51
Date
04/23/2010Pubmed ID
20408976Pubmed Central ID
PMC2910147DOI
10.1111/j.1751-1097.2010.00722.xScopus ID
2-s2.0-77954415077 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
Singlet oxygen attack on cholesterol (Ch), a prominent monounsaturated lipid of mammalian cell plasma membranes, gives rise to three hydroperoxide (ChOOH) isomers, 5alpha-OOH, 6alpha-OOH and 6beta-OOH, the latter two in lower yield than 5alpha-OOH, and 6alpha-OOH in lowest yield. A third possible positional isomer, 7alpha-OOH and 7beta-OOH, is produced by free radical attack. In the presence of iron and ascorbate (Fe/AH), 5alpha-OOH or 6beta-OOH in phosphatidylcholine/Ch/ChOOH (20:15:1 by mol) liposomes was reduced to its corresponding alcohol, the rate constant being approximately the same for both ChOOHs. Using [(14)C]Ch as an in situ probe, we found that liposomal 5alpha-OOH readily set off free radical-mediated (chain) peroxidation reactions when exposed to Fe/AH, whereas 6beta-OOH under the same conditions did not. Moreover, liposomal 5alpha-OOH triggered robust chain peroxidation in [(14)C]Ch-labeled L1210 cells, leading to cell death, whereas 6beta-OOH was essentially inert in this regard. Thus, 5alpha-OOH and 6beta-OOH undergo iron-catalyzed reductive turnover, but only the former can provoke toxic membrane damage. These novel findings have important implications for UVA-induced photodamage in Ch-rich tissues like skin and eye, where (1)O(2) often plays a major role.
Author List
Korytowski W, Schmitt JC, Girotti AWAuthor
Albert Girotti PhD, MS Emeritus Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Membrane
Cholesterol
Free Radicals
Lipid Peroxidation
Liposomes
Mice
Peroxides
Photochemistry
Singlet Oxygen
Tumor Cells, Cultured
