Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO.
Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO.
Photochem Photobiol. 2020 Jul;96(4):870-876. doi: 10.1111/php.13228. Epub 2020 Apr 13.
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 ) 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 ) 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.
中波紫外线（UVB）辐射被认为是皮肤致癌作用的罪魁祸首。我们之前的研究表明，具有抗氧化和抗炎能力的半胱氨酸衍生物布西拉明（N-[2-巯基-2-甲基丙酰基]-L-半胱氨酸）可防止 UVB 诱导的小鼠皮肤 p53 激活和炎症反应。由于 MAPK 信号通路调节 p53 的表达和激活，因此我们在此使用人皮肤角质形成细胞系 HaCaT 在体外和 SKH-1 无毛小鼠皮肤在体内确定了布西拉明对 UVB 介导的 MAPK 激活的影响。单次低剂量的 UVB（30 mJ cm ）导致 HaCaT 细胞中 JNK/MAPK 磷酸化和 caspase-3 切割增加。然而，JNK 激活和 caspase-3 切割被生理剂量的布西拉明（25 和 100 µm）预处理的 HaCaT 细胞抑制。与这些结果一致，布西拉明预处理（20 mg kg）在 UVB 暴露后 6-12 和 24 小时分别抑制了小鼠皮肤表皮细胞中的 JNK/MAPK 和 ERK/MAPK 激活。此外，布西拉明减弱了 UVB 诱导的 Ki-67 阳性细胞和 cleaved caspase-3 阳性细胞在小鼠皮肤中的表达。这些发现表明布西拉明抑制了 UVB 诱导的 MAPK 信号转导、细胞增殖和细胞凋亡。结合我们之前的报告，我们提供了布西拉明具有抗 UV 暴露的光保护作用的证据。
