Bucillamine Inhibits UVB‐Induced MAPK Activation and Apoptosis in Human HaCaT Keratinocytes and SKH‐1 Hairless Mouse Skin. (13th April 2020)

• Record Type: Journal Article
• Authors: Anwar, Adil; Anwar, Hiba; Yamauchi, Takeshi; Tseng, Ryan; Agarwal, Rajesh; Horwitz, Lawrence D; Zhai, Zili; Fujita, Mayumi
• Is Part Of: Photochemistry and photobiology. Volume 96:Number 4(2020)
• Page Start: 870
• Page End: 876
• Publication Date: 2020-04-13
• Subjects: Photochemistry -- Periodicals; Light -- Physiological effect -- Periodicals; 541.35
• DOI: 10.1111/php.13228
• Languages: English
• ISSNs: 0031-8655

Abstract

Abstract: Ultraviolet B (UVB) radiation is known as a culprit in skin carcinogenesis. We have previously reported that bucillamine (N‐[2‐mercapto‐2‐methylpropionyl]‐L‐cysteine), a cysteine derivative with antioxidant and anti‐inflammatory capacity, protects against UVB‐induced p53 activation and inflammatory responses in mouse skin. Since MAPK signaling pathways regulate p53 expression and activation, here we determined bucillamine effect on UVB‐mediated MAPK activation in vitro using human skin keratinocyte cell line HaCaT and in vivo using SKH‐1 hairless mouse skin. A single low dose of UVB (30 mJ cm −2 ) resulted in increased JNK/MAPK phosphorylation and caspase‐3 cleavage in HaCaT cells. However, JNK activation and casaspe‐3 cleavage were inhibited by pretreatment of HaCaT cells with physiological doses of bucillamine (25 and 100 µm ). Consistent with these results, bucillamine pretreatment in mice (20 mg kg −1 ) inhibited JNK/MAPK and ERK/MAPK activation in skin epidermal cells at 6–12 and 24 h, respectively, after UVB exposure. Moreover, bucillamine attenuated UVB‐induced Ki‐67‐positive cells and cleaved caspase‐3‐positive cells in mouse skin. These findings demonstrate that bucillamine inhibits UVB‐induced MAPK signaling, cell proliferation and apoptosis. Together with our previous report, we provide evidence that bucillamine has a photoprotective effect against UV exposure. Abstract : Bucillamine, a cysteine derivative with antioxidant and anti‐inflammatory capacity, protects against UVB‐induced apoptosis via inhibition of MAPK activation in human HaCaT keratinocytes and SKH‐1 hairless mouse skin.