Cholesterol Peroxidation as a Special Type of Lipid Oxidation in Photodynamic Systems

Abstract

Like other unsaturated lipids in cell membranes and lipoproteins, cholesterol (Ch) is susceptible to oxidative modification, including photodynamic oxidation. There is a sustained interest in the pathogenic properties of Ch oxides such as those generated by photooxidation. Singlet oxygen ( O )-mediated Ch photooxidation (Type II mechanism) gives rise to three hydroperoxide (ChOOH) isomers: 5α-OOH, 6α-OOH and 6β-OOH, the 5α-OOH yield far exceeding that of the others. 5α-OOH detection is relatively straightforward and serves as a definitive indicator of O involvement in a reaction, photochemical or otherwise. Like all lipid hydroperoxides (LOOHs), ChOOHs can disrupt membrane or lipoprotein structure/function on their own, but subsequent light-independent reactions may either intensify or attenuate such effects. Such reactions include (1) one-electron reduction to redox-active free radical intermediates, (2) two-electron reduction to redox-silent alcohols and (3) translocation to other lipid compartments, where (1) or (2) may take place. In addition to these effects, ChOOHs may act as signaling molecules in reactions that affect cell fates. Although processes a-c have been well studied for ChOOHs, signaling activity is still poorly understood compared with that of hydrogen peroxide. This review focuses on these various aspects Ch photoperoxidation and its biological consequences.

Ultrastructural Aspects of Photodynamic Inactivation of Highly Pathogenic Avian H5N8 Influenza Virus

“…Using a high photosensitizer concentration (4 µM), we observed irregular virion shapes which likely reflect virion membrane damage. One explanation is that the hydroperoxides of cholesterol and other lipids disrupt viral membranes [32] and induce lipid membrane damage.…”

Secondary Dark Reactions Following Photodynamic Treatment are More Damaging Than Previously Thought

“…Deciphering downstream reactions following photodynamic treatment can be problematic. The detailed cholesterol photooxidation studies conducted by Girotti and Korytowski provide this insight into these very reactions.…”

“…Their studies reported in Photochemistry & Photobiology describe the fate of cholesterol hydroperoxides produced in sensitized photooxidation. That fate provides key insight for the secondary reactions, such as the cholesterol hydroperoxides dark decomposition, which can be more cytotoxic than the primary reactions.…”

“…The work of Girotti et al . reveals a key point, that may be viewed as like a one two punch, that is, light‐dependent/dark‐dependent processes that occur one after another. Such initial light and subsequent dark processes can account for deeper understanding of and improve our control of photodynamic effects.…”

Lysine Reacts with Cholesterol Hydroperoxide to Form Secosterol Aldehydes and Lysine-Secosterol Aldehyde Adducts

“…According to the recently postulated pathway for amide-type adduct formation [13], secosterol 2 would react with lysine to successively form carbinolamine 7, Schiff's base 8, peroxide intermediate 9, and amide-type adduct 10 (Scheme 2). Analogously to the conversion of hydroperoxide 4 to secosterol aldehydes 2 and 3 (Scheme 1), Cholesterol-6 (α and β)-hydroperoxides 11 formed as minor products of photosensitized cholesterol oxidation [19] are expected to undergo lysine-catalyzed cyclization to dioxetane 6 and thus also afford secosterol aldehydes 2 and 3 (Scheme 3).…”