Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotuke, Tochigi 329-0498, Japan.
J Dermatol Sci. 2010 May;58(2):136-42. doi: 10.1016/j.jdermsci.2010.02.009. Epub 2010 Feb 18.
Repetitive exposure of the skin to UVA radiation elicits sagging more frequently than wrinkling, which is mainly attributed to its biochemical mechanism to up-regulate the expression of matrix-metalloproteinase (MMP)-1 and skin fibroblast elastase (SFE)/neutral endopeptidase (NEP), respectively.
In this study, we examined the effects of a potent antioxidant, astaxanthin (AX), on the induction of MMP-1 and SFE by UVA treatment of cultured human dermal fibroblasts.
Those effects were assessed by real-time RT-PCR, Western blotting and enzymic activity assays.
UVA radiation elicited a significant increase in the gene expression of MMP-1 as well as SFE/NEP (to a lesser extent) which was followed by distinct increases in their protein and enzymatic activity levels. The addition of AX at concentrations of 4-8 microM immediately after UVA exposure significantly attenuated the induction of MMP-1 and SFE/NEP expression elicited by UVA at the gene, protein and activity levels although both the UVA stimulation and the subsequent AX inhibition were greater for MMP-1 than for SFE/NEP. Analysis of the UVA-induced release of cytokines revealed that UVA significantly stimulated only the secretion of IL-6 among the cytokines tested and that AX significantly diminished only the IL-6 secretion.
These findings indicate that, based on different effective concentrations of AX, a major mode of action leading to the inhibition elicited by AX depends on inhibition of UVA effects of the reactive oxygen species-directed signaling cascade, but not on interruption of the IL-6-mediated signaling cascade. We hypothesize that AX would have a significant benefit on protecting against UVA-induced skin photo-aging such as sagging and wrinkles.
皮肤反复暴露于 UVA 辐射会导致皮肤松弛,而不是皱纹,这主要归因于其生化机制分别上调基质金属蛋白酶(MMP)-1和皮肤成纤维细胞弹性蛋白酶(SFE)/中性内肽酶(NEP)的表达。
本研究旨在探讨一种强效抗氧化剂虾青素(AX)对 UVA 处理培养的人真皮成纤维细胞中 MMP-1 和 SFE 诱导的影响。
通过实时 RT-PCR、Western 印迹和酶活性测定评估这些影响。
UVA 辐射可显著增加 MMP-1 以及 SFE/NEP 的基因表达(程度较小),随后其蛋白和酶活性水平明显增加。UVA 照射后立即添加浓度为 4-8μM 的 AX,可显著减弱 UVA 在基因、蛋白和活性水平上诱导的 MMP-1 和 SFE/NEP 表达,尽管 UVA 刺激和随后的 AX 抑制对 MMP-1 的作用大于 SFE/NEP。对 UVA 诱导的细胞因子释放的分析表明,UVA 仅显著刺激了所测试的细胞因子中 IL-6 的分泌,而 AX 仅显著减少了 IL-6 的分泌。
这些发现表明,基于不同有效浓度的 AX,抑制作用的主要作用模式取决于抑制 UVA 对活性氧导向信号级联的影响,而不是中断 IL-6 介导的信号级联。我们假设 AX 对预防 UVA 诱导的皮肤光老化(如松弛和皱纹)具有显著益处。