Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Korea.
Division of Bioengineering, Incheon National University, Incheon 22012, Korea.
Int J Mol Sci. 2019 Jun 22;20(12):3055. doi: 10.3390/ijms20123055.
Caffeic acid phenethyl ester (CAPE), a naturally occurring bioactive compound, displays anti-inflammatory, anti-carcinogenic, and anti-microbial effects. However, the effect of CAPE on skin photoaging is unknown. Herein, we investigated the inhibitory effect of CAPE against ultraviolet (UV) irradiation-mediated matrix metalloproteinase (MMP)-1 expression and its underlying molecular mechanism. CAPE treatment suppressed UV-induced MMP-1 levels in both human dermal fibroblasts (HDF) and human skin tissues. While CAPE did not display any significant effects against the upstream regulatory pathways of MMP-1, CAPE was capable of reversing UV-mediated epigenetic modifications. CAPE suppressed UV-induced acetyl-histone H3 (Lys9) as well as total lysine acetylation in HDF cells. Similarly, CAPE also attenuated UV-induced lysine acetylations in human skin tissues, suggesting that the CAPE-mediated epigenetic alterations can be recapitulated in ex vivo conditions. CAPE was found to attenuate UV-induced histone acetyltransferase (HAT) activity in HDF. Notably, CAPE was able to directly inhibit the activity of several HATs including p300, CREP-binding protein (CBP), and p300/CBP-associated factor (PCAF), further confirming that CAPE can function as an epigenetic modulator. Thus, our study suggests that CAPE maybe a promising agent for the prevention of skin photoaging via targeting HATs.
咖啡酸苯乙酯（CAPE）是一种天然存在的生物活性化合物，具有抗炎、抗癌和抗菌作用。然而，CAPE 对皮肤光老化的影响尚不清楚。在此，我们研究了 CAPE 对紫外线（UV）照射介导的基质金属蛋白酶（MMP）-1 表达的抑制作用及其潜在的分子机制。CAPE 处理抑制了人真皮成纤维细胞（HDF）和人皮肤组织中 UV 诱导的 MMP-1 水平。虽然 CAPE 对 MMP-1 的上游调控途径没有显示出任何显著影响，但 CAPE 能够逆转 UV 介导的表观遗传修饰。CAPE 抑制了 HDF 细胞中 UV 诱导的乙酰化组蛋白 H3（Lys9）和总赖氨酸乙酰化。同样，CAPE 也减弱了人皮肤组织中 UV 诱导的赖氨酸乙酰化，表明 CAPE 介导的表观遗传改变可以在离体条件下重现。CAPE 被发现能够减弱 HDF 中 UV 诱导的组蛋白乙酰转移酶（HAT）活性。值得注意的是，CAPE 能够直接抑制几种 HAT 的活性，包括 p300、CREB 结合蛋白（CBP）和 p300/CBP 相关因子（PCAF），进一步证实 CAPE 可以作为一种表观遗传调节剂。因此，我们的研究表明，CAPE 可能是一种有前途的预防皮肤光老化的药物，通过靶向 HATs。
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