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Bucillamine Inhibits UVB-Induced MAPK Activation and Apoptosis in Human HaCaT Keratinocytes and SKH-1 Hairless Mouse Skin
Journal article   Peer reviewed

Bucillamine Inhibits UVB-Induced MAPK Activation and Apoptosis in Human HaCaT Keratinocytes and SKH-1 Hairless Mouse Skin

Adil Anwar, Hiba Anwar, Takeshi Yamauchi, Ryan Tseng, Rajesh Agarwal, Lawrence D. Horwitz, Zili Zhai and Mayumi Fujita
Photochemistry and photobiology, Vol.96(4), pp.870-876
07/2020
DOI: 10.1111/php.13228
PMCID: PMC7387142
PMID: 32077107

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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 mu m). 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.
Biochemistry & Molecular Biology Biophysics Life Sciences & Biomedicine Science & Technology

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