Berrak Rencüzoğullari Özge, Tornaci Selay, Çelik Yağmur, Ciroğlu Nayat Narot, Obakan Yerlikaya Pınar, Arisan Elif Damla, Çoker Gürkan Ajda
Department of Molecular Biology and Genetics, İstanbul Kültür University, İstanbul, Turkey.
Institute of Biotechnology, Gebze Technical University, Gebze, Turkey.
Turk J Biol. 2022 Dec 15;47(1):29-43. doi: 10.55730/1300-0152.2639. eCollection 2023.
Human growth hormone (GH) is crucial modulator of cellular metabolisms, including cell proliferation and organ development, by stimulating insulin-like growth factor-1 (IGF-1), which has various functions such as cell proliferation, tissue growth, survival, or neuroprotection. Therefore, GH is implicated as a critical player in the cell and can enhance neurogenesis and provide neuroprotection during the treatment of neurological diseases such as Parkinson's disease (PD). In this study, the neuroprotective role of GH was investigated in rotenone-induced PD models for the first time. Both SH-SY5Y and SK-N-AS neuroblastoma cells were exposed to rotenone to mimic PD pathogenesis as stated in previous studies. Our data demonstrated that overexpression of GH led to the resistance of the SH-SY5Y and SK-N-AS cell lines to rotenone treatment. The levels of ER stress markers, CHOP, PERK, XBP-1, and ATF6, were higher in wt cells than GH+ SH-SY5Y cells. However, the level of autophagy markers LC3 increased and the levels of reactive oxygen species (ROS) decreased with the overexpression of GH. Furthermore, while rotenone significantly increased the SubG1 population in the cell cycle of SH-SY5Y wt cells, there was a minor alteration in GH+ cell population. Concomitantly, the levels of the proapoptotic marker, cleaved-PARP, and positive staining of Annexin V in SH-SY5Y wt cells were higher after rotenone treatment. Together, these results revealed that overexpression of GH enhanced the autophagy response by triggering the ER stress of SH-SY5Y cells to rotenone exposure and showed a neuroprotective effect in vitro PD models.
人生长激素（GH）是细胞代谢的关键调节因子，通过刺激胰岛素样生长因子-1（IGF-1）来调节细胞代谢，包括细胞增殖和器官发育。IGF-1具有多种功能，如细胞增殖、组织生长、细胞存活或神经保护。因此，GH被认为是细胞中的关键因子，在帕金森病（PD）等神经疾病的治疗过程中，它可以增强神经发生并提供神经保护。在本研究中，首次在鱼藤酮诱导的PD模型中研究了GH的神经保护作用。如先前研究所述，将SH-SY5Y和SK-N-AS神经母细胞瘤细胞均暴露于鱼藤酮以模拟PD发病机制。我们的数据表明，GH的过表达导致SH-SY5Y和SK-N-AS细胞系对鱼藤酮处理产生抗性。野生型细胞中内质网应激标志物CHOP、PERK、XBP-1和ATF6的水平高于GH+SH-SY5Y细胞。然而，随着GH的过表达，自噬标志物LC3的水平升高，活性氧（ROS）水平降低。此外，虽然鱼藤酮显著增加了SH-SY5Y野生型细胞细胞周期中SubG1期的细胞群体，但GH+细胞群体仅有轻微变化。同时，鱼藤酮处理后，SH-SY5Y野生型细胞中促凋亡标志物cleaved-PARP的水平和膜联蛋白V的阳性染色更高。总之，这些结果表明，GH的过表达通过触发SH-SY5Y细胞对鱼藤酮暴露的内质网应激来增强自噬反应，并在体外PD模型中显示出神经保护作用。
