a Department of Neurology, Key-Disciplines Laboratory Clinical Medicine of Henan, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China.
b Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University , Zhengzhou , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2764-2774. doi: 10.1080/21691401.2019.1636805.
Parkinson's disease (PD) is a common age-related neurodegenerative disease resulted from the progressive degeneration of dopaminergic neurons in the pars compacta region of substantia nigra. The goal of this study was to investigate the effects and mechanisms of long noncoding RNA (lncRNA) HAGLROS on the apoptosis and autophagy in PD. The MPTP-induced PD mouse model and MPP-intoxicated SH-SY5Y cell model were established, and the expression levels of HAGLROS and miR-100 were determined. Subsequently, the effects of suppression of HAGLROS on apoptosis and autophagy in MPTP-induced PD mouse model and in MPP-intoxicated SH-SY5Y cells were investigated. In addition, the association between HAGLROS and miR-100 as well as HAGLROS and activation of phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in MPP-intoxicated SH-SY5Y cells was explored. HAGLROS was increasingly expressed in MPTP-induced PD mouse model and MPP-intoxicated SH-SY5Y cells and suppression of HAGLRO decreased apoptosis and autophagy in both and PD models. Further studies showed that HAGLRO negatively regulated miR-100 expression, and HAGLROS regulated apoptosis and autophagy of MPP-intoxicated SH-SY5Y cells through sponging miR-100. Moreover, ATG10 was identified as a target of miR-100. Besides, suppression of HAGLROS alleviated MPP-intoxicated SH-SY5Y cell injury by activating PI3K/AKT/mTOR pathway. Our findings reveal that upregulation of HAGLROS may contribute to the development of PD via inhibiting apoptosis and autophagy, which may be achieved by regulating miR-100/ATG10 axis and PI3K/AKT/mTOR pathway activation.
帕金森病（PD）是一种常见的与年龄相关的神经退行性疾病，源于黑质致密部多巴胺能神经元的进行性退化。本研究旨在探讨长链非编码 RNA（lncRNA）HAGLROS 对 PD 中细胞凋亡和自噬的作用及机制。建立了 MPTP 诱导的 PD 小鼠模型和 MPP 诱导的 SH-SY5Y 细胞模型，测定了 HAGLROS 和 miR-100 的表达水平。随后，研究了抑制 HAGLROS 对 MPTP 诱导的 PD 小鼠模型和 MPP 诱导的 SH-SY5Y 细胞中细胞凋亡和自噬的影响。此外，还探讨了 HAGLROS 与 miR-100 以及 HAGLROS 与 MPP 诱导的 SH-SY5Y 细胞中磷酸肌醇 3 激酶/蛋白激酶 B/哺乳动物雷帕霉素靶蛋白（PI3K/Akt/mTOR）通路激活之间的关系。HAGLROS 在 MPTP 诱导的 PD 小鼠模型和 MPP 诱导的 SH-SY5Y 细胞中表达上调，抑制 HAGLRO 可减少两种 PD 模型中的细胞凋亡和自噬。进一步研究表明，HAGLROS 负调控 miR-100 的表达，HAGLROS 通过海绵 miR-100 调节 MPP 诱导的 SH-SY5Y 细胞的凋亡和自噬。此外，ATG10 被鉴定为 miR-100 的靶基因。此外，抑制 HAGLROS 通过激活 PI3K/AKT/mTOR 通路缓解 MPP 诱导的 SH-SY5Y 细胞损伤。我们的研究结果表明，HAGLROS 的上调可能通过抑制细胞凋亡和自噬来促进 PD 的发生，这可能是通过调节 miR-100/ATG10 轴和 PI3K/AKT/mTOR 通路的激活来实现的。
