論文の公開元へSqualene secondary oxidation products: structural elucidation, mechanism of formation, presence, and effect on the human skin.
概要
Over the years, lipid hydroperoxides (LOOHs) and their mechanism of formation have been extensively studied as primary products of lipid oxidation, and have long been linked to different pathogenesis such as accelerated aging, and inflammatory diseases[1–3]. Squalene (SQ) (SQ, Fig.1), the most abundant among skin surface lipids (SSLs) (12%), and a precursor of natural steroids[4–6], due to its terpenic nature, has been reported to undergo singlet oxygen (1O2) oxidation on the skin to yield six SQ-monohydroperoxide (SQ-OOH) isomers as its primary oxidation products (Fig.1) [7]. Previously, it has been demonstrated that the six SQ-OOH isomers increased following the exposure of the skin to sunlight, further confirming the photosensitized 1O2 oxidation of SQ [8]. However, studies on its secondary oxidation products and the mechanism involved in their formation are rather limited to its breakdown products, mainly upon interaction with ozone [9–11]; no significant reports on the formation of higher molecular weight secondary oxidation products could be found.
Taking into account the constant exposure of the skin to photons (e.g., sunlight, LEDs), and the unstable nature of hydroperoxides, in the present study (Chapter 1, section 1), it is proposed that SQ-OOH isomers would undergo further modifications to yield cyclic peroxides as the first secondary oxidation products. Several lipid oxidation mechanisms leading to the formation of LOOHs such as the alder ene reaction involved in the 1O2 oxidation, and the classic radical initiated lipid peroxidation have been well documented. However, only a few studies attempted and have demonstrated concrete mechanisms of further oxidation of LOOHs. The Russell mechanism, for example, illustrates the generation of 1O2 from the self-reaction of peroxyl radicals. Nevertheless, evidence is still lacking with regard to the mechanism leading to the formation of lipid cyclic peroxides. To this end, a detailed investigation of the mechanism involved in the formation of SQ cyclic peroxides was also carried out (Chapters 1, section 2).
The skin forms the first defense line that protects the organism against external stressors and pathogens due to its hydrophobic coating with SSLs [12]. Dysregulation of SSLs’ function has been linked to their oxidation, resulting in serious skin conditions such as premature aging, melanoma, inflammatory and allergic diseases [13– 15]. Oxidation of SQ on the skin has been reported to cause significant abnormalities such as hyperpigmentation, inflammation, and formation of wrinkles[16–19]. However, the effects of individual SQ-OOH isomers and the herein newly reported SQ cyclic peroxide are unknown. Therefore, basal and differentiated phenotypes of HaCaT cells were used in this study (Chapter 3) to assess their effect.
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