Abstract
The human skin has an important role in barrier function. Ultraviolet rays (UV) from sunlight exposure can cause cell apoptosis in the skin epidermis, resulting in the disruption of the barrier. Previously, we have demonstrated that BNIP3 stimulates autophagy in epidermal keratinocytes and has a protective effect in these cells upon UVB irradiation. In this study, we found that the accumulation of reactive oxygen species (ROS) by UVB irradiation was sufficient to trigger the activation of JNK and ERK mitogen-activated protein kinase (MAPK) in human primary epidermal keratinocytes. In turn, activated JNK and ERK MAPK mediated the upregulation of BNIP3 expression. Treatment with an antioxidant reagent or a specific inhibitor of MAPK, U0126, and a JNK inhibitor significantly attenuated the expression of BNIP3 triggered by UVB, followed by the induction of cell death by apoptosis. Furthermore, UVB-induced apoptosis was significantly stimulated by chloroquine or bafilomycin A1, an inhibitor of autophagy. Moreover, BNIP3 was required for the degradation of dysfunctional mitochondria upon UVB irradiation. These data clearly indicated that BNIP3-induced autophagy, which occurs via UVB-generated ROS-mediated JNK and ERK MAPK activation, has a crucial role in the protection of the skin epidermis against UVB irradiation.
Highlights
The stratified epithelium of the skin acts as a physical barrier against pathogens, toxins, and harmful irradiation
It has been reported that BNIP3 can induce apoptosis, necrosis, or autophagy depending on the cellular context.[3]
To reveal the molecular mechanism by which BNIP3 expression is activated by UVB irradiation, we first focused on reactive oxygen species (ROS) because previous studies suggested that ROS are accumulated following UVB exposure.[15,16]
Summary
The stratified epithelium of the skin acts as a physical barrier against pathogens, toxins, and harmful irradiation. Apoptosis serves as a protective mechanism by eliminating cells with damaged organelles, proteins, and/or DNA to reduce the risk of tumor formation; on the other hand, excessive apoptosis is associated with disruption of epidermal barrier function and inflammation of the skin. Received 27.7.16; revised 05.12.16; accepted 22.12.16; Edited by M Agostini reported to induce autophagy, resulting in cytoprotection in multiple cell types.[10,11] For example, stress-causing DNA damage can be induced by several factors including chemical substances, ionizing radiation, reactive oxygen species (ROS), and UV irradiation
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