Assessing Photosensitized Membrane Damage: Available Tools and Comprehensive Mechanisms^†

Abstract

Lipids are important targets of the photosensitized oxidation reactions, forming important signaling molecules, disorganizing and permeabilizing membranes, and consequently inducing a variety of biological responses. Although the initial steps of the photosensitized oxidative damage in lipids are known to occur by both Type I and Type II mechanisms, the progression of the peroxidation reaction, which leads to important end-point biological responses, is poorly known. There are many experimental tools used to study the products of lipid oxidation, but neither the methods nor their resulting observations were critically compared. In this article, we will review the tools most frequently used and the key concepts raised by them in order to rationalize a comprehensive model for the initiation and the progression steps of the photoinduced lipid oxidation.

Sunlight‐Induced Degradation of Dissolved Ethyl‐Parathion and Coupled Molecular Toxicity Investigation

“…In the present study, the significant increase in peroxidation of linoleic acid, a lipid membrane monomer (Figure 6), represents a characteristic marker of reactive oxygen species (ROS)‐mediated membrane‐lipid peroxidation typical in cellular systems [27,28] . Given the observed potential for sunlight‐dependent formation of O 2 .– (Figure 5) and the literature evidence that O 2 .– can initiate lipid peroxidation, [29–31] we hypothesize that the observed increase in linoleic acid peroxidation in response to sunlight exposure (Figure 6) occurred via a type‐I photochemical reaction. As observed in the O 2 .– formation assay, there was no significant influence of EP at 24 mg/L versus the 0 mg/L EP control on linoleic acid peroxidation (Figure 6) indicating that EP was not the primary photosensitizing agent in the experimental exposure.…”

“…Superoxide dismutase (SOD) rapidly catalyzes the reduction of O 2 .– to oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ), [25] thus the significant reduction of O 2 .– when 100 units of SOD were included in the sunlight exposure assays provides validation that O 2 .– was actively being formed which were subsequently reduced by SOD (Figure 5). The photoreaction of a photosensitizer plus oxygen can form O 2 .– which may react directly with lipid membranes, ultimately causing lipid peroxidation in what is termed a type‐I photochemical reaction [26] . As an important caveat to this specific association among the O 2 .– generation assay and lipid peroxidation results, it should be noted that the assays were conducted independently of one another with each including unique reagent sets and chemistry conditions required for each individual assay to function correctly.…”

“…The photoreaction of a photosensitizer plus oxygen can form O 2 .-which may react directly with lipid membranes, ultimately causing lipid peroxidation in what is termed a type-I photochemical reaction. [26] As an important caveat to this specific association among the O 2 .generation assay and lipid peroxidation results, it should be noted that the assays were conducted independently of one another with each including unique reagent sets and chemistry conditions required for each individual assay to function correctly. Additionally, the assays were conducted on different dates where ambient sunlight intensity and temperature conditions were different.…”

Mechanisms of Phototoxic Effects of Cationic Porphyrins on Human Cells In Vitro

“…Given the weak hydrophobicity of the porphyrins used [ 21 ], we can assume that interaction with protein targets on the membrane is crucial. One can even assume that the targets are formed during the interaction, as described in [ 33 , 34 , 35 ].…”

Lipid peroxidation drives liquid-liquid phase separation and disrupts raft protein partitioning in biological membranes

“…Thus, disturbances in plasma membrane raft homeostasis are likely to be among the cellular defects that occur as ferroptosis is initiated and executed. PUFAs are also susceptible to react with reactive oxygen species which are produced by enzymatic (e.g., 12/15 lipoxygenase) processes, as well as those produced by photosensitizers and other mechanisms [23, 131]. An important goal for the future will be to establish whether these differing peroxidation mechanisms have similar or distinct effects on raft homeostasis.…”