Fig. 4

Signaling pathways of reactive oxygen species (ROS) in ultraviolet (UV)-induced skin photodamage. ROS regulate DNA damage and cell signaling pathways, and cause an imbalance of skin oxidants and antioxidants, which accelerates skin photodamage. Unrepaired damaged DNA, including cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6–4) pyrimidone photoproducts [(6–4)PPs], can cause cell death. Moreover, ROS signaling regulates transcription factors, such as AP-1 and nuclear factor-kappa B (NF-κB), inducing the expression of matrix metalloproteinases (MMPs), upregulating the expression of inflammatory factors, such as IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and downregulating TGF-β expression and Smad signaling. Thus, extracellular matrix genes and collagen type I alpha1 (COL1A1), elastin (ELN), and hyaluronan synthase 2 (HAS2) are downregulated. Moreover, collagen types I and III are degraded into ¾ and ¼ fragments, respectively, while type IV collagen is degraded into non-collagen components and elastic fibers, resulting in accelerated aging in the form of skin relaxation, deepened wrinkles, and decreased skin elasticity. ROS are also directly or indirectly involved in UV-induced mitochondrial apoptosis by affecting the expression of Bcl-2 and Bcl-x in the mitochondria, thus inducing the release of cytochrome c (cyt-c). Once released, cyt-c functions with the apoptotic peptidase activating factor 1 (Apaf-1) to form a type of apoptotic body that recruits and activates caspase 9 to initiate caspase 3-dependent apoptosis