Swiader Audrey, Camaré Caroline, Guerby Paul, Salvayre Robert, Negre-Salvayre Anne
Inserm U1048, Institute for Metabolic and Cardiovascular Diseases, 31432 Toulouse, France.
University of Toulouse III - Paul Sabatier, 31062 Toulouse, France.
Antioxidants (Basel). 2021 Feb 28;10(3):365. doi: 10.3390/antiox10030365.
Solar ultraviolet A (UV-A) radiation promotes a huge variety of damages on connective tissues and dermal fibroblasts, including cellular senescence, a major contributor of skin photoaging. The mechanisms of skin photoaging evoked by UV-A partly involve the generation of reactive oxygen species and lipid peroxidation. We previously reported that 4-hydroxynonenal (HNE), a lipid peroxidation-derived aldehyde, forms adducts on elastin in the skins of UV-A irradiated hairless mice, possibly contributing to actinic elastosis. In the present study, we investigated whether and how HNE promotes fibroblast senescence in skin photoaging. Dermal fibroblasts of skins from UV-A-exposed hairless mice exhibited an increased number of γH2AX foci characteristic of cell senescence, together with an accumulation of HNE adducts partly colocalizing with the cytoskeletal protein vimentin. Murine fibroblasts exposed to UV-A radiation (two cycles of 15 J/cm), or HNE (30 µM, 4 h), exhibited senescence patterns characterized by an increased γH2AX foci expression, an accumulation of acetylated proteins, and a decreased expression of the sirtuin SIRT1. HNE adducts were detected on vimentin in cultured fibroblasts irradiated by UV-A or incubated with HNE. The HNE scavenger carnosine prevented both vimentin modification and fibroblast senescence evoked by HNE in vitro and in the skins of UV-A-exposed mice. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in fibroblast senescence, and confirm the protective effect of carnosine in skin photoaging.
太阳紫外线A（UV-A）辐射会对结缔组织和真皮成纤维细胞造成多种损害，包括细胞衰老，而细胞衰老是皮肤光老化的主要原因。UV-A引起皮肤光老化的机制部分涉及活性氧的产生和脂质过氧化。我们之前报道过，4-羟基壬烯醛（HNE）是一种脂质过氧化衍生的醛，它会在UV-A照射的无毛小鼠皮肤中的弹性蛋白上形成加合物，这可能导致光化性弹力纤维病。在本研究中，我们调查了HNE是否以及如何在皮肤光老化中促进成纤维细胞衰老。来自UV-A照射的无毛小鼠皮肤的真皮成纤维细胞表现出细胞衰老特有的γH2AX焦点数量增加，同时HNE加合物的积累部分与细胞骨架蛋白波形蛋白共定位。暴露于UV-A辐射（两个15 J/cm周期）或HNE（30 µM，4小时）的小鼠成纤维细胞表现出衰老模式，其特征是γH2AX焦点表达增加、乙酰化蛋白积累以及沉默调节蛋白SIRT1表达降低。在UV-A照射或与HNE孵育的培养成纤维细胞的波形蛋白上检测到HNE加合物。HNE清除剂肌肽可在体外以及UV-A照射小鼠的皮肤中防止波形蛋白修饰和成纤维细胞衰老。总之，这些数据强调了HNE和脂质过氧化衍生的醛在成纤维细胞衰老中的作用，并证实了肌肽对皮肤光老化的保护作用。
