Dai Hui-Yu, Chang Ming-Xiu, Sun Ling
Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Transl Neurosci. 2023 Jul 25;14(1):20220296. doi: 10.1515/tnsci-2022-0296. eCollection 2023 Jan 1.
Parkinson's disease (PD) is the second most common neurodegenerative disease with complex pathogenesis. Although HOXA transcript antisense RNA myeloid-specific 1 (HOTAIRM1) is upregulated in PD, its exact role in HOTAIRM1 is seldom reported. The purpose of this study is to research the effect of HOTAIRM1 on 1-methyl-4-phenylpyridonium (MPP)-induced cytotoxicity and oxidative stress in SH-SY5Y cells.
SH-SY5Y cells were treated with MPP at various concentrations or time points to induce SH-SY5Y cytotoxicity, so as to determine the optimal MPP concentration and time point. HOTAIRM1 expression upon MPP treatment was analyzed through qRT-PCR. Next, HOTAIRM1 was downregulated to observe the variance of SH-SY5Y cell viability, apoptosis, oxidative stress-related indexes, and protein levels of the Nrf2/HO-1 pathway. In addition, rescue experiments were carried out to assess the role of Nrf2 silencing in HOTAIRM1 knockdown on MPP-induced oxidative stress in SH-SY5Y cells.
MPP treatment-induced cytotoxicity and upregulated HOTAIRM1 expression in SH-SY5Y cells in a dose- and time-dependent manner. Mechanically, HOTAIRM1 knockdown enhanced cell viability, limited apoptosis, and oxidative stress, therefore protecting SH-SY5Y cells from MPP-induced SH-SY5Y cytotoxicity. On the other hand, HOTAIRM1 knockdown activated the protein levels of Nrf2 and HO-1. Nrf2 silencing could counteract the neuroprotective effect of HOTAIRM1 knockdown on PD model.
Our data demonstrated that HOTAIRM1 knockdown could inhibit apoptosis and oxidative stress and activated the Nrf2/HO-1 pathway, therefore exerting neuroprotective effect on the PD cell model.
帕金森病（PD）是第二常见的神经退行性疾病，其发病机制复杂。尽管HOXA转录本反义RNA髓系特异性1（HOTAIRM1）在PD中上调，但其在HOTAIRM1中的确切作用鲜有报道。本研究旨在探讨HOTAIRM1对1-甲基-4-苯基吡啶离子（MPP）诱导的SH-SY5Y细胞毒性和氧化应激的影响。
用不同浓度或时间点的MPP处理SH-SY5Y细胞以诱导其细胞毒性，从而确定最佳MPP浓度和时间点。通过qRT-PCR分析MPP处理后HOTAIRM1的表达。接下来，下调HOTAIRM1以观察SH-SY5Y细胞活力、凋亡、氧化应激相关指标以及Nrf2/HO-1通路蛋白水平的变化。此外，进行挽救实验以评估Nrf2沉默在HOTAIRM1敲低对MPP诱导的SH-SY5Y细胞氧化应激中的作用。
MPP处理以剂量和时间依赖性方式诱导SH-SY5Y细胞毒性并上调HOTAIRM1表达。机制上，HOTAIRM1敲低增强了细胞活力，限制了凋亡和氧化应激，从而保护SH-SY5Y细胞免受MPP诱导的细胞毒性。另一方面，HOTAIRM1敲低激活了Nrf2和HO-1的蛋白水平。Nrf2沉默可抵消HOTAIRM1敲低对PD模型的神经保护作用。
我们的数据表明，HOTAIRM1敲低可抑制凋亡和氧化应激并激活Nrf2/HO-1通路，从而对PD细胞模型发挥神经保护作用。
