Mechanism of UV Induced ROS Generation: Photosensitization

The primary mechanism of UV induced skin aging is the production and generation of reactive oxygen species (ROS). ROS/free radicals is one of the main causes of chronologic and photo skin aging. ROS damages and oxidizes biomacromolecules and cellular components. ROS also are intracellular signals which activate and regulate transcriptions factors and genes involved in the molecular mechanism of the skin aging process. One mechanism of UV induced ROS generation is via photosensitization. The molecular mechanism linking the photon absorption and ROS generation has been elucidated while the detailed mechanism seems to be elusive. Photosensitization is the process that the absorption of photon by the chromophores in the molecule cause the chromophore to change to the photoexcited state from the electronic ground state. When there is no subsequent energy dissipation or photon emission after the photon absorption. The absorbed energy will initiate chemical reactions leading to the formation of reactive intermediates and photoproduct where the absorbed photon energy is converted to chemical energy and the chromophores return to the electronic ground state. The Photoreactive intermediate react with substrate molecules including DNA bases (type I photosensitization reaction) or molecular oxygen (type II photosensitization reaction) leading to ROS formation. Both Type I and Type II mechanism can cause the formation of superoxide anion which will produce H2O2 (hydrogen peroxide) by spontaneous or enzyme catalyzed dismutation. Thus, it is the physical nature of the incident solar photons and the chemical nature of the absorbing chromophore in skin that determine the biological effects of the ROS generation. Most of the solar UV energy incident on the skin is from the UVA region which is a deep penetrating UV in the skin. Photosensitization by endogenous non-DNA chromophores of skin appears to be a key primary mechanism of light driven ROS production in skin although UV irradiation may also cause the electron leakage at the mitochondria respiratory chain and thereby increase the production of ROS byproduct in the aerobic metabolism or by activating existing NADPH oxidase activity through UV induced intracellular calcium influx (see post “Mechanism of UV Induced ROS Generation: NADPH Oxidase Activation”).

The endogenous photosensitizers in the skin are primary intermediates for the ROS formation in the photo oxidative stress mechanism of skin aging. Human skin is an abundant source of numerous chromophores with strong absorption particularly in the UVA region. The endogenous photosensitizers include a multitude of chemical structures, pathways of formation, skin localization and photochemical mechanisms of action. Photosensitizers in the skin exists both as constitutive structural and functional intra- and extracellular molecules and as dynamically generated accumulated molecules as a result of posttranslational modification and crosslinking of skin structural proteins and as a result of photooxidative and carbonyl stress by spontaneous chemical modification of intra- and extracellular molecules. A 3-step model of skin photosensitization process has been proposed to illustrate general UV-induced ROS formation mechanism in photo skin aging. Step I is the formation of photosensitizer by enzymatic and spontaneous reaction pathways leading to the accumulation of photosensitizer chromophores, particularly on skin structural proteins of the extracellular matrix. Step II is the photosensitizer activation via generation of the photoexcited state of the sensitizer upon absorption of photons. Photochemical reaction cascades available to the particular photosensitizer are initiated depending on the local pH, solute concentrations, water activity, oxygen
partial pressure, and surrounding target molecules. Photoactivation of endogenous sensitizers occurs throughout skin, ranges from nuclear to extracellular compartments. Step III is the execution of photosensitization which is the process of ROS/free radical induced aging and skin aging and the accumulation of photoproducts formed by photooxidation of target molecules

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