核因子E2相关因子2信号通路及其在紫外线致皮肤蛋白氧化应激损伤中的作用

Nuclear factor-E2-related factor 2 signaling pathway and its role in oxidative protein damage caused by ultraviolet in skin

紫外线照射产生活性氧及自由基,与皮肤光老化、皮肤癌等皮肤光损伤疾病的发生相关.活性氧及自由基不仅通过攻击氨基酸主侧链等方式氧化蛋白质,而且能够激活丝裂原活化蛋白激酶产生基质金属蛋白酶,降解皮肤结缔组织中的胶原蛋白等蛋白质,使皮肤发生光损伤.核因子E2相关因子2信号通路是细胞氧化应激反应的核心调控机构,在应激条件下,激活核因子E2相关因子2,通过调节抗氧化酶类和Ⅱ相解毒酶基因的表达,清除过多的核因子E2相关因子2和自由基,抑制基质金属蛋白酶的分泌,保护蛋白质,增强机体抗氧化应激的能力,对皮肤起到保护作用.核因子E2相关因子2信号通路及其调控机制与皮肤蛋白氧化应激损伤间关系的深入研究,将有利于寻找蛋白氧化应激损伤导致的相关皮肤光损伤疾病新的有效的治疗防御措施.

Ultraviolet （UV） radiation can induce the production of reactive oxygen species （ROS） and free radicals that are implicated in photodamage-related diseases such as skin photoaging and skin cancer.ROS and free radicals not only can oxidize proteins through attacking amino acid main and side chains,but also can activate the mitogen-activated protein kinase to produce matrix metalloproteinase （MMP） followed by the degradation of proteins such as collagen protein in cutaneous connective tissue,and finally lead to skin photodamage.Nuclear factor-E2-related factor 2 （Nrf2） signaling pathway is a key regulator of cellular response to oxidative stress.Under oxidative stress,Nrf2 is activated,and then removes excessive Nrf2 and free radicals by regulating the expressions of antioxidases and phase Ⅱ detoxifying enzyme,protect proteins by inhibiting the secretion of MMP,and finally protect skin from damage by enhancing the ability against oxidative stress.Therefore,to learn the Nrf2 signaling pathway,its regulation mechanism and relationship with oxidative protein damage in skin may offer new directions for the treatment of photodamage-related skin diseases caused by oxidative protein damage.