Previous studies have indicated that NaIO₃ induces intracellular reactive oxygen species (ROS) production and has been used as a model for age-related macular degeneration (AMD) due to the selective retinal pigment epithelium (RPE) cell damage it induces. Beta-mangostin (BM) is a xanthone-type natural compound isolated from Cratoxylum arborescens. The influence of BM on NaIO₃-induced oxidative stress damage in ARPE-19 cells has not yet been elucidated. In this study, we investigated how BM protects ARPE-19 cells from NaIO₃-induced ROS-mediated apoptosis. Our results revealed that BM notably improved cell viability and prevented ARPE-19 cell mitochondrial dysfunction mediated-apoptosis induced by NaIO₃; it was mediated by significantly reduced NaIO₃-upregulated ROS, cellular H₂O₂ production and improved downregulated glutathione and catalase activities. Furthermore, we found that BM could suppress the expression of Bax, cleaved PARP, and cleaved caspase-3 by decreasing phosphorylation of MEK/ERK and p53 expression in NaIO₃-induced ARPE-19 cells. At the same time, we also used MEK inhibitors (PD98059) to confirm the above phenomenon. Moreover, our animal experiments revealed that BM prevented NaIO₃ from causing retinal deformation; it led to thicker outer and inner nuclear layers and downregulated cleaved caspase-3 expression compared to the group receiving NaIO₃ only. Collectively, these results suggest that BM can protect the RPE and retina from NaIO₃-induced apoptosis through ROS-mediated mitochondrial dysfunction involving the MEK/ERK and p53 signaling pathways.

中文翻译：

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β-山竹素通过 MEK/ERK 和 p53 信号通路对碘酸钠诱导的视网膜 ROS 介导的细胞凋亡的保护作用


先前的研究表明，NaIO ₃会诱导细胞内活性氧（ROS）的产生，并且由于其诱导的选择性视网膜色素上皮（RPE）细胞损伤而被用作年龄相关性黄斑变性（AMD）的模型。 Beta-mangostin (BM) 是从Cratoxylum arborescens中分离出的氧杂蒽酮型天然化合物。 BM 对 NaIO ₃诱导的 ARPE-19 细胞氧化应激损伤的影响尚未阐明。在本研究中，我们研究了 BM 如何保护 ARPE-19 细胞免受 NaIO ₃诱导的 ROS 介导的细胞凋亡。我们的结果表明，BM 显着提高细胞活力，并防止 NaIO ₃诱导的 ARPE-19 细胞线粒体功能障碍介导的细胞凋亡；它是通过显着减少 NaIO ₃上调的 ROS、细胞 H ₂ O ₂的产生以及改善下调的谷胱甘肽和过氧化氢酶活性来介导的。此外，我们发现BM可以通过降低NaIO ₃诱导的ARPE-19细胞中MEK/ERK的磷酸化和p53表达来抑制Bax、裂解的PARP和裂解的caspase-3的表达。同时，我们还使用MEK抑制剂（PD98059）来证实上述现象。此外，我们的动物实验表明，BM 可以防止 NaIO ₃引起视网膜变形；与仅接受NaIO ₃的组相比，它导致外核层和内核层更厚，并且下调了cleaved caspase-3 的表达。 总的来说，这些结果表明，BM 可以通过涉及 MEK/ERK 和 p53 信号通路的 ROS 介导的线粒体功能障碍，保护 RPE 和视网膜免受 NaIO ₃诱导的细胞凋亡。