Dalle Carbonare M, Pathak M A
Department of Dermatology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
J Photochem Photobiol B. 1992 Jun 30;14(1-2):105-24. doi: 10.1016/1011-1344(92)85086-a.
In this paper, the role of reactive oxygen species in photoaging is presented. Many photosensitizing agents are known to generate reactive oxygen species (singlet oxygen (1O2), superoxide anion (O2.-) and .OH radicals). Although photoaging (dermatoheliosis) of human skin is caused by UVB and UVA radiation, the hypothesis tested here in the pathogenesis of photoaging of human skin is the free radical theory involving the generation of reactive oxygen species by UVA (320-400 nm) radiation and their damaging oxidative effects on cutaneous collagen and other model proteins. The UVA-generated reactive oxygen species cause cross-linking of proteins (e.g. collagen), oxidation of sulfydryl groups causing disulfide cross-links, oxidative inactivation of certain enzymes causing functional impairment of cells (fibroblasts, keratinocytes, melanocytes, Langerhans cells) and liberation of proteases, collagenase and elastase. The skin-damaging effects of UVA appear to result from type II, oxygen-mediated photodynamic reactions in which UVA or near-UV radiation in the presence of certain photosensitizing chromophores (e.g., riboflavin, porphyrins, nicotinamide adenine dinucleotide phosphate (NADPH), etc.) leads to the formation of reactive oxygen species (1O2, O2.-, .OH). Four specific observations are presented to illustrate the concept: (1) the production of 1O2 and O2.- by UVB, UVA and UVA plus photosensitizing agents (such as riboflavin, porphyrin and 3-carbethoxypsoralens) as a function of UV exposure dose, the sensitizer concentration and the pH of the irradiated solution; (2) the formation of protein cross-links in collagen, catalase and superoxide dismutase by 1O2 and O2.- (.OH) and the resulting denaturation of proteins and enzyme activities as a function of UVA exposure dose; (3) the protective role of selective quenchers of 1O2 and O2.- (e.g. alpha-tocopherol acetate, beta-carotene, sodium azide, ascorbic acid, etc.) against the photoinactivation of enzymes and the prevention of the protein cross-linking reaction; (4) the possible usefulness of certain antioxidants or quenchers that interact with the UVA-induced generation of reactive oxygen species in the amelioration of the process of photoaging.
本文介绍了活性氧在光老化中的作用。已知许多光敏剂会产生活性氧（单线态氧（¹O₂）、超氧阴离子（O₂⁻·）和·OH自由基）。虽然人类皮肤的光老化（皮肤日光性老化）是由中波紫外线（UVB）和长波紫外线（UVA）辐射引起的，但本文在此测试的人类皮肤光老化发病机制的假说是自由基理论，该理论涉及UVA（320 - 400纳米）辐射产生活性氧及其对皮肤胶原蛋白和其他模型蛋白的氧化损伤作用。UVA产生的活性氧会导致蛋白质交联（如胶原蛋白）、巯基氧化形成二硫键交联、某些酶的氧化失活导致细胞（成纤维细胞、角质形成细胞、黑素细胞、朗格汉斯细胞）功能受损以及蛋白酶、胶原酶和弹性蛋白酶的释放。UVA对皮肤的损伤作用似乎源于II型氧介导的光动力反应，其中UVA或近紫外线辐射在某些光敏发色团（如核黄素、卟啉、烟酰胺腺嘌呤二核苷酸磷酸（NADPH）等）存在下会导致活性氧（¹O₂、O₂⁻·、·OH）的形成。本文给出了四个具体观察结果来说明这一概念：（1）UVB、UVA以及UVA加光敏剂（如核黄素、卟啉和3 - 乙氧羰基补骨脂素）产生¹O₂和O₂⁻·的情况，作为紫外线暴露剂量、敏化剂浓度和照射溶液pH值的函数；（2）¹O₂和O₂⁻·（·OH）在胶原蛋白、过氧化氢酶和超氧化物歧化酶中形成蛋白质交联以及由此导致的蛋白质变性和酶活性变化，作为UVA暴露剂量的函数；（3）¹O₂和O₂⁻·的选择性猝灭剂（如醋酸生育酚、β - 胡萝卜素、叠氮化钠、抗坏血酸等）对酶光失活的保护作用以及对蛋白质交联反应的预防作用；（4）某些抗氧化剂或猝灭剂与UVA诱导的活性氧生成相互作用在改善光老化过程中可能的有用性。
