Introduction Excessive exposure to ultraviolet UV irradiatio

Introduction Excessive exposure to ultraviolet (UV) irradiation from the sun injures human skin, which might lead to premature aging and skin pathologies [1], [2]. Chronic exposure to UV (especially ultraviolet-B, UVB) irradiation could profoundly affect the skin epidermis, interfering with the keratinocyte maturation [3]. Reactive oxygen species (ROS) generated by UVB irradiation at the cell membrane in human skin is an essential risk factor of photodamage [4], [5]. Therefore, ROS scavengers and antioxidants have been gradually used to protect the skin Losartan sale against UVB irradiation. Endoplasmic reticulum (ER) is the organelle where proteins are synthesized, folded, and modified. Various stress, such as hypoxia, ischemia, and starvation, would interfere with the function of ER and induce ER stress. Accumulating evidence suggests that high concentrations of ROS induced by UVB irradiation lead to abnormal ER homeostasis and even ER stress [6], [7], [8]. It has been reported that UVB irradiation could accelerate ROS production and then induce ER stress in HaCaT cells [8]. Therefore, ER has been recognized as a potential target for antioxidants in the treatment of UVB-induced damages. Polypeptides have multiple advantages compared with chemical drugs, such as better targeting and less side effects [9], making a promising group of potential new drugs. Polypeptide from Chlamys farreri (PCF) is a novel marine bioactive peptide extracted from Chinese scallop. PCF is a soluble octapeptide with a molecular weight of 879Da, consisting of 8 amino acids, namely, Pro, Asn, Ser, Thr, Arg, Hyl, Cys, and Gly. Our recent studies have demonstrated that PCF has anti-oxidative effects, which can protect human HaCaT cells from UVB irradiation via scavenging ROS and inhibiting apoptosis [10], [11], [12], [13], [14], [15]. However, the effects of PCF on ER stress under UVB irradiation have not yet been clearly elucidated. In this study, the ER-related protective effects of PCF in HaCaT cells exposed to UVB irradiation and the related mechanisms were investigated.
Materials and methods
Results
Discussion Exposure of skin to UVB might result in the excessive generation and uncontrolled release of ROS, which is involved in the pathogenesis of human skin disorders. Accumulating evidence suggests a direct link between ROS production and ER stress. Previous studies showed that PCF possessed anti-oxidant and anti-apoptotic properties, and the molecular mechanisms involve ROS scavenging [10], COX-2 [11], CD95 [12], NF-B [11], [13], TGF-β1 [14], iNOS [14], [15], and HSP90 [15]. In this study, the effects of PCF on ER stress in HaCaT cells following UVB irradiation were investigated. Our results demonstrated that the apoptosis rate was dramatically elevated in HaCaT cells following irradiation. The treatment of 4-PBA and NAC could obviously retrieve the cell viability, with NAC exhibiting a more effective effect than 4-PBA. These results suggest that ROS and ER stress might play important roles in UVB-induced damages in HaCaT cells. The protective effects of PCF on the UVB-irradiated HaCaT cells were further investigated. Our result indicated that PCF could increase the cell viability and decrease the apoptosis rate in HaCaT cells subjected to UVB irradiation. ROS is a byproduct of metabolism within cellular organelles, including ER and mitochondria, due to toxic agents and/or stimuli such as UVB irradiation. In ER, ROS is produced from the electron transfer from protein thiol to molecular oxygen by Ero-1a and PDI, which function in maintaining the ER redox homeostasis [16]. After identifying the involvement of ROS and ER stress in UVB-induced damages in HaCaT cells, the effects of PCF on the expression of Ero-1a and PDI were then evaluated. Our results indicated that the ER redox homeostasis was disturbed by UVB irradiation, and the expression levels of Ero-1a and PDI were sharply decreased in HaCaT cells. However, the treatment of PCF elevated the expression of Ero-1a and PDI, indicating that PCF could restore the ER redox homeostasis through enhancing the expressions of Ero-1s and PDI and inhibiting the generation of ROS.