Photo-protective effect of sargachromenol against UVB radiation-induced damage through modulating cellular antioxidant systems and apoptosis in human keratinocytes
Introduction
Skin, the largest human organ, is the protective covering of the body and is daily exposed to environmental stress sources. Skin is naturally exposed to excessive levels of ultraviolet (UV) radiation, resulting in the generation of debilitating levels of intracellular reactive oxygen species (ROS) (Lee et al., 2014).
Ultraviolet B (UVB, 280–320 nm) radiation stimulates ROS generation and oxidative stress in the skin (Hewage et al., 2015, Martinez et al., 2015). Chronic UVB exposure induces inflammation including erythema, premature aging, edema formation, immunosuppression, and skin cancer. UVB accelerates photo-oxidative reactions that can alter anti-ROS-sensitive signaling pathways, which ultimately increases the cellular ROS level (Yogianti et al., 2012). Moreover, toxic products basically derived via protein carbonylation and lipid peroxidation cause extensive oxidative damage. UVB irradiation especially damages keratinocytes of the epidermis through the generation of DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), which has been implicated in the risk of skin cancer (Choi et al., 2014). Interleukin-6 and tumor necrosis factor-α are inflammatory cytokines that were previously reported to be associated with UVB exposure (Heck et al., 2004). Accumulated studies emphasize that mitogen-activated protein kinases (MAPKs) are essential for UVB-induced apoptosis of human keratinocytes and UV-induced cellular responses such as skin cancer.
Skin has the ability to counteract UVB-induced ROS via efficient antioxidant defense mechanisms. When ROS generation overwhelms this antioxidant defense capacity, the ability of the skin to recover from damage caused by ROS is impaired, leading to oxidative damage of cellular macromolecules such as DNA, proteins, and lipids (Saw et al., 2014).
Nowadays, natural compounds are focused upon as a means to improve human health due to their low toxicity and safety. Meanwhile, the supplementation of dietary botanical antioxidants against UVB-induced oxidative injuries has been frequently studied. Sargachromenol (SC, Fig. 1A), a compound isolated from the brown marine alga Sargassum micracanthum, has various pharmacological properties, including antioxidant and antiviral activities (Yang et al., 2013). SC has also neuroactive properties via promoting neurite outgrowth and supporting the survival of neuronal PC12D cells (Hur et al., 2008).
Although many marine algae have anti-inflammatory and antioxidant activities, very few studies have elucidated the underlying molecular mechanisms. Therefore, the purpose of the present study was to determine whether SC can enhance antioxidant properties in human keratinocytes and to elucidate its cytoprotective role against UVB-induced oxidative damage. Here, we found a novel function of SC to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) and to target antioxidant enzymes. Moreover, it was revealed that the MAPK signaling pathway is involved in the cytoprotective mechanism of SC.
Section snippets
Reagents
SC isolated from Sargassum macrocarpum was kindly donated by Professor Nam Ho Lee of Jeju National University (Jeju, Republic of Korea). Diphenyl-2-picrylhydrazyl (DPPH), 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Hoechst 33342, N-acetyl cysteine (NAC), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), and anti-actin antibody were purchased from Sigma-Aldrich Corporation (St. Louis, MO, USA). Diphenyl-1-pyrenylphosphine (DPPP)
Effect of SC on UVB-induced ROS generation
At the experimental concentrations of 2.5, 5, 10, 20, and 40 μM SC didn’t show any significant cytotoxicity on HaCaT keratinocytes (Fig. 1B). SC showed the 16%, 21%, 25%, 33%, and 51% of DPPH radical scavenging effect at 2.5, 5, 10, 20, and 40 μM of SC, respectively, comparing with that obtained with the positive control, NAC (1 mM). H2O2-induced intracellular ROS-scavenging activity was measured at different concentrations of SC. This activity was 29% with 40 μM SC, whereas the corresponding
Discussion
UVB radiation emitted from the sun penetrates the dermis of the skin and is epidemiologically proven to be a main cause of skin cancers. Recently, various plant-derived phytochemicals have been extensively investigated because they possess anti-inflammatory and antioxidant properties, and thus exert photo-protective effects on the skin (Kim et al., 2014). S. micracanthum is a widespread marine alga and a number of biologically important substances are isolated. Among these, SC is one of the
Acknowledgments
This work was supported by a National Research Foundation of Korea Grant funded by the Korean Government (MEST) (NRF-C1ABA001-2011-0021037).
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