Role of reactive oxygen species in ultraviolet-induced photodamage of the skin

Abstract

Reactive oxygen species (ROS), such as superoxides (O₂ •-) and hydroxyl groups (OH·), are short-lived molecules containing unpaired electrons. Intracellular ROS are believed to be mainly produced by the mitochondria and NADPH oxidase (NOX) and can be associated with various physiological processes, such as proliferation, cell signaling, and oxygen homeostasis. In recent years, many studies have indicated that ROS play crucial roles in regulating ultraviolet (UV)-induced photodamage of the skin, including exogenous aging, which accounts for 80% of aging. However, to the best of our knowledge, the detailed signaling pathways, especially those related to the mechanisms underlying apoptosis in which ROS are involved have not been reviewed previously. In this review, we elaborate on the biological characteristics of ROS and its role in regulating UV-induced photodamage of the skin.

Keywords: Apoptosis; DNA; Inflammation; Photodamage; Reactive oxygen species; Ultraviolet.

Fig. 1

Depths of ultraviolet (UV) radiation (UVR). UVC, with the shortest wavelength (100–290 nm) and highest energy, is mostly blocked by the ozone layer and rarely reaches human skin. Contrastingly, both UVB and UVA can penetrate the ozone layer. UVA, with the longest wavelength (320–400 nm) and lowest energy, can reach deep into the dermis, whereas UVB (wavelength: 290–320 nm) mostly reaches the surface of the dermis

Fig. 2

Effects of reactive oxygen species (ROS) depend on the dose and persistence of the particles. A low level of ROS can lead to mutation, a medium level of ROS can cause senescence, and a high level of ROS usually cause cell death, such as apoptosis and necrosis

Fig. 3

Production and regulation of reactive oxygen species (ROS). Mitochondria and NADPH oxidases (NOXs) are the two main contributors of endogenous ROS. O₂• − is formed from molecular O₂ following the acceptance of a single electron from the electron transport chain (ETC) in the mitochondria or from NOXs. Superoxide dismutase (SOD) enzymes convert O₂ •− into H₂O₂, which can then be reduced and converted by peroxiredoxin (PRX), glutathione peroxidase (GPX), and catalase to form H₂O and OH•. The latter is extremely reactive and causes damage to DNA, proteins, and lipids

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

Fig. 5

Signaling pathway of MAPK in UV-induced skin photodamage affected by ROS. UV irradiation can induce ROS and then has an impact on activating the MAPK pathway within the cells. Then, the downstream factors extracellular signal-regulated kinase (ERK), P38 kinase, and c-Jun N-terminal kinase (JNK) in the MAPK pathway can enter the nucleus and regulate transcription factors, such as AP-1 and NF-κB, inducing the expression of MMPs, upregulating the expression of inflammatory factors, such as IL-1β, IL-6, TNF-α, and downregulating TGF-β expression