Department of Neurology, The Affiliated ZhongShan Hospital of Dalian University, Dalian, China.
Department of Imaging, The Affiliated ZhongShan Hospital of Dalian University, Dalian, China.
Brain Behav. 2021 Aug;11(8):e2278. doi: 10.1002/brb3.2278. Epub 2021 Jul 23.
Parkinson's disease (PD) is a severe neurodegenerative disease with high morbidity in the elderly population. 6-OHDA-induced cell senescence is reported to be involved in the pathogenesis of PD. Ramelteon is an oral hypnotic agent that specifically targets the receptors of the suprachiasmatic nucleus in the human hypothalamus. Here, an investigation is made to see whether Ramelteon possesses a beneficial effect against 6-OHDA-induced cellular senescence in human SH-SY5Y neuronal cells.
The release of LDH was detected to assess cytotoxicity and flow cytometry was conducted to evaluate the cell cycle. The telomerase activity and the SA-β-Gal assay were performed to determine the state of cell senescence. Oxidative stress was evaluated by detecting the release of H O . The expressions of p21, p53, and Nrf2 were measured using the qRT-PCR and Western blotting assay. siRNA technology was used to knock down the expression level of Nrf2 in SH-SY5Y neuronal cells.
First, it was found that Ramelteon mitigated cell cycle arrest in the G0/G1 phase in 6-OHDA-challenged SH-SY5Y neuronal cells. Second, treatment with Ramelteon alleviated cellular senescence in 6-OHDA-treated SH-SY5Y neuronal cells by increasing telomerase activity and reducing the activity of SA-β-gal. It was also found that Ramelteon reduced the expressions of p21 and p53. Notably, Ramelteon attenuated 6-OHDA-induced oxidative stress by increasing the expression of Nrf2. Silencing of Nrf2 abolished the protective effects of Ramelteon against 6-OHDA-induced cellular senescence. Based on these findings, it was concluded that Ramelteon alleviated 6-OHDA-induced cellular senescence by increasing the expression of Nrf2 in human SH-SY5Y neuronal cells.
Ramelteon protected against 6-OHDA-induced cellular senescence in human SH-SY5Y neuronal cells through activating the Nrf2 signaling pathway.
帕金森病（PD）是一种在老年人群中发病率较高的严重神经退行性疾病。据报道，6-OHDA 诱导的细胞衰老与 PD 的发病机制有关。雷美替胺是一种口服催眠药，专门针对人类下丘脑视交叉上核的受体。在这里，我们研究了雷美替胺是否对人 SH-SY5Y 神经元细胞中 6-OHDA 诱导的细胞衰老具有有益作用。
通过检测 LDH 的释放来评估细胞毒性，通过流式细胞术评估细胞周期。通过端粒酶活性和 SA-β-Gal 测定来确定细胞衰老状态。通过检测 H2O2 的释放来评估氧化应激。使用 qRT-PCR 和 Western blotting 测定来测量 p21、p53 和 Nrf2 的表达。使用 siRNA 技术敲低 SH-SY5Y 神经元细胞中 Nrf2 的表达水平。
首先，发现雷美替胺减轻了 6-OHDA 应激的 SH-SY5Y 神经元细胞中 G0/G1 期的细胞周期停滞。其次，雷美替胺通过增加端粒酶活性和降低 SA-β-gal 活性，减轻了 6-OHDA 处理的 SH-SY5Y 神经元细胞中的细胞衰老。还发现雷美替胺降低了 p21 和 p53 的表达。值得注意的是，雷美替胺通过增加 Nrf2 的表达来减轻 6-OHDA 诱导的氧化应激。沉默 Nrf2 消除了雷美替胺对 6-OHDA 诱导的细胞衰老的保护作用。基于这些发现，可以得出结论，雷美替胺通过增加人 SH-SY5Y 神经元细胞中 Nrf2 的表达来减轻 6-OHDA 诱导的细胞衰老。
雷美替胺通过激活 Nrf2 信号通路来保护人 SH-SY5Y 神经元细胞免受 6-OHDA 诱导的细胞衰老。
