Department of Nanomaterials Engineering, Pusan National University, Busan 46241, Republic of Korea.
Bio‑IT Fusion Technology Research Institute, Pusan National University, Busan 46241, Republic of Korea.
Mol Med Rep. 2018 Dec;18(6):5182-5190. doi: 10.3892/mmr.2018.9538. Epub 2018 Oct 8.
Oxidative stress‑induced cellular senescence is an important contributor to the pathogenesis of age‑related macular degeneration (AMD). Characteristics of premature cellular senescence include a loss of proliferation, change in cell shape, irreversible cell cycle arrest, and elevated senescence‑associated β‑galactosidase (SA‑β‑gal) activity. It was hypothesized that lutein may have anti‑senescence potential and may be useful as a treatment for AMD. In the present study, premature cellular senescence was induced in ARPE‑19 cells via treatment with H2O2 and the effects of lutein application were confirmed by observing cell morphology, lysosome contents, reactive oxygen species (ROS) generation and SA‑β‑gal activity, and cell cycle progression. The protein expression was also analyzed via western blotting in order to identify the affected signaling pathways. The results revealed that H2O2 treatment induced premature cellular senescence in ARPE‑19 cells, as evidenced by an increased production of ROS and SA‑β‑gal, altered lysosome contents, changed cellular morphology and arrested cell cycle progression. However, when treated with lutein, ARPE‑19 cells were effectively protected from these H2O2‑induced effects. Western blot analysis revealed that lutein induced the expression of heme oxygenase‑1, NAD(P)H quinone dehydrogenase 1, sirtuin (SIRT)‑1, and SIRT3. Together, the results indicated that lutein protects cells from cellular senescence induced by oxidative stress; therefore, it may be able to suppress the progression of AMD. In addition, our increased understanding of the pathways through which lutein acts is useful for the development of novel therapies for the treatment of oxidative stress‑associated retinal disease.
氧化应激诱导的细胞衰老（Senescent）是年龄相关性黄斑变性（AMD）发病机制的重要因素。过早衰老细胞的特征包括增殖能力丧失、细胞形状改变、细胞周期不可逆停滞以及衰老相关β-半乳糖苷酶（SA-β-gal）活性升高。有研究假设叶黄素（Lutein）可能具有抗衰老作用，可作为 AMD 的治疗方法。本研究通过过氧化氢（H2O2）处理 ARPE-19 细胞以诱导过早衰老，并通过观察细胞形态、溶酶体含量、活性氧（ROS）生成和 SA-β-gal 活性以及细胞周期进程，证实了叶黄素的应用效果。还通过 Western blot 分析了蛋白质表达，以确定受影响的信号通路。结果表明，H2O2 处理诱导 ARPE-19 细胞过早衰老，表现为 ROS 和 SA-β-gal 生成增加、溶酶体含量改变、细胞形态改变以及细胞周期停滞。然而，用叶黄素处理时，ARPE-19 细胞有效抵御了这些 H2O2 诱导的作用。Western blot 分析显示，叶黄素诱导血红素加氧酶-1（HO-1）、烟酰胺腺嘌呤二核苷酸磷酸（NAD（P）H）醌氧化还原酶 1（NQO1）、Sirtuin 1（SIRT1）和 Sirtuin 3（SIRT3）的表达。综上，结果表明叶黄素可保护细胞免受氧化应激诱导的衰老；因此，它可能能够抑制 AMD 的进展。此外，我们对叶黄素作用途径的深入了解有助于开发治疗氧化应激相关视网膜疾病的新疗法。
