The chemical- and photo- toxicity of chromophore retinal on cells have long been debated. Although we recently showed that retinal and blue light exposure interrupt cellular signaling, a comprehensive study examining molecular underpinnings of this perturbation and its consequences to cellular fate is lacking. Here, we report molecular evidence for blue light excited-retinal induced oxidative damage of polyunsaturated lipid anchors in membrane-interacting signaling molecules and DNA damage in cells using live-cell imaging and in vitro experimentation. The incurred molecular damage irreversibly disrupted subcellular localization of these molecules, a crucial criterion for their signaling. We further show retinal accumulation in lipid-bilayers of cell membranes could enhance the lifetime of retinal in cells. Comparative response-signatures suggest that retinal triggers reactions upon photoexcitation similar to photodynamic therapy agents and generate reactive oxygen species in cells. Additionally, data also shows that exposing retinal-containing cells to sunlight induces substantial cytotoxicity. Collectively, our results explain a likely in vivo mechanism and reaction conditions under which bio-available retinal in physiological light conditions damages cells.

中文翻译：

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蓝光触发的视网膜光化学和细胞毒性。

生色团视网膜对细胞的化学和光毒性早已引起争议。尽管我们最近发现视网膜和蓝光暴露会中断细胞信号传导，但仍缺乏一项全面的研究来研究这种微扰的分子基础及其对细胞命运的影响。在这里，我们报告分子证据表明，使用活细胞成像和体外实验，膜相互作用信号分子中的多不饱和脂质锚定物受到蓝光激发的视网膜诱导的氧化损伤以及细胞中的DNA损伤。发生的分子损伤不可逆地破坏了这些分子的亚细胞定位，这是其信号传导的关键标准。我们进一步表明，视网膜在细胞膜脂质双层中的积累可以延长视网膜在细胞中的寿命。比较的响应特征表明，视网膜在光激发时会触发类似于光动力治疗剂的反应，并在细胞中产生活性氧。此外，数据还显示，将含视网膜的细胞暴露于阳光下会诱导大量的细胞毒性。总的来说，我们的结果解释了可能的体内机制和反应条件，在生理光条件下生物可利用的视网膜会损害细胞。