Oxidative stress-induced neuronal damage is a main cause of ischemia/reperfusion injury. Curcumin (Cur), the principal constituent extracted from dried rhizomes of Curcuma longa L. (turmeric), exhibits excellent antioxidant effects. Previous studies have indicated that miR-1287-5p was downregulated in patients with ischemic stroke. Additionally, we predicted that Lon Peptidase 2, Peroxisomal (LONP2), which is involved in oxidative stress regulation, is targeted by miR-1287-5p. The aim of the current study is to investigate the effect of Cur on ischemia/reperfusion damage and its underlying mechanism. To mimic ischemia/reperfusion damage environment, SH-SY5Y cells were subjected to oxygen-glucose-deprivation/reperfusion (OGD/R). OGD/R treatment downregulated miR-1287-5p and upregulated LONP2 in SH-SY5Y cells, but Cur alleviated OGD/R-induced oxidative damage and reversed the effect of OGD/R on the expression of miR-1287-5p and LONP2. Furthermore, we confirmed the interactive relationship between miR-1287-5p and LONP2 (negative regulation). We revealed that miR-1287-5p overexpression alleviated OGD/R-induced oxidative damage alleviation, similar to the effect of Cur. MiR-1287-5p inhibition accentuated OGD/R-induced oxidative damage in SH-SY5Y cells, which was reversed by Cur. The expression of LONP2 in OGD/R-treated SH-SY5Y cells was decreased by miR-1287-5p overexpression and increased by miR-1287-5p inhibition, and Cur counteracted the increase in LONP2 expression induced by miR-1287-5p inhibition. In conclusion, we suggest that Cur alleviates OGD/R-induced oxidative damage in SH-SY5Y cells by regulating the miR-1287-5p/LONP2 axis. The findings provide a theoretical basis for the clinical application of curcumin.

中文翻译：

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姜黄素通过调节 SH-SY5Y 细胞中的 miR-1287-5p/LONP2 轴减轻缺氧/再灌注诱导的氧化损伤


氧化应激引起的神经元损伤是缺血/再灌注损伤的主要原因。姜黄素 (Cur) 是从姜黄 (Curcuma longa L.) 的干燥根茎中提取的主要成分，具有优异的抗氧化作用。先前的研究表明，缺血性中风患者中 miR-1287-5p 下调。此外，我们预测参与氧化应激调节的 Lon 肽酶 2，过氧化物酶体 (LONP2) 是 miR-1287-5p 的靶标。本研究的目的是探讨Cur对缺血/再灌注损伤的影响及其潜在机制。为了模拟缺血/再灌注损伤环境，对 SH-SY5Y 细胞进行氧-葡萄糖剥夺/再灌注（OGD/R）。 OGD/R处理下调SH-SY5Y细胞中的miR-1287-5p并上调LONP2，但Cur减轻OGD/R诱导的氧化损伤并逆转OGD/R对miR-1287-5p和LONP2表达的影响。此外，我们证实了 miR-1287-5p 和 LONP2（负调控）之间的相互作用关系。我们发现，miR-1287-5p 过表达可减轻 OGD/R 诱导的氧化损伤，类似于 Cur 的作用。 MiR-1287-5p 抑制加剧了 OGD/R 诱导的 SH-SY5Y 细胞氧化损伤，而 Cur 可以逆转这种损伤。 OGD/R处理的SH-SY5Y细胞中LONP2的表达因miR-1287-5p过表达而降低，并因miR-1287-5p抑制而增加，并且Cur抵消了miR-1287-5p抑制诱导的LONP2表达的增加。总之，我们认为 Cur 通过调节 miR-1287-5p/LONP2 轴减轻 OGD/R 诱导的 SH-SY5Y 细胞氧化损伤。研究结果为姜黄素的临床应用提供了理论依据。