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Molecular Mechanism of Platelet-Derived Growth Factor (PDGF)-BB-Mediated Protection Against MPP + Toxicity in SH-SY5Y Cells
Journal of Molecular Neuroscience ( IF 3.1 ) Pub Date : 2020-11-09 , DOI: 10.1007/s12031-020-01735-0
Huan Chen 1, 2 , Yan Teng 1, 2 , Zhihao Liu 2 , Fan Geng 2 , Xingmin Chen 2 , Haisong Jiang 1 , Jing Yang 2 , Min Zheng 2 , Ziyan Wang 2 , Lu Yang 2
Affiliation  

As an important endogenous growth factor, PDGF-BB can effectively promote neurogenesis, thus is considered as a potential agent for Parkinson’s disease (PD) therapy. However, the protective function of PDGF-BB on neuronal cells, especially the molecular mechanism, remains less clear, which is needed to explore before its clinical practice. In this study, we investigated the function and mechanism of PDGF-BB against 1-methyl-4-phenylpyridinium (MPP+) toxicity in SH-SY5Y cells, a widely used cellular tool for PD-related molecular study. Our results indicated that PDGF-BB exerts a prominent protective effect against neurotoxin MPP+-triggered ROS generation and cellular loss. We further dissected the molecular mechanism involved in this process by using specific pharmacological inhibitors and validated that the distinct signaling pathways PI3K/Akt/GSK-3β and MEK/ERK are involved in the process against MPP+ toxicity upon PDGF-BB treatment. We also detected that activation of upstream PI3K/Akt/GSK-3β and MER/ERK signaling pathways contribute to phosphorylation and nuclear translocation of the downstream effector cyclic response element-binding protein (CREB), a known transcription factor to exhibit neuroprotective and growth-promoting effects. Using genetic approach, we further confirmed that the activation of CREB is involved in PDGF-BB-mediated protection in MPP+-exposed SH-SY5Y cells. Together, these data demonstrated the protective effect of PDGF-BB in MPP+-mediated toxicity in SH-SY5Y cells and verified the involved molecular mechanism in PDGF-BB-mediated neuroprotection.



中文翻译:

SH-SY5Y 细胞中血小板衍生生长因子 (PDGF)-BB 介导的针对 MPP + 毒性的保护的分子机制

作为一种重要的内源性生长因子,PDGF-BB 可以有效促进神经发生,因此被认为是帕金森病 (PD) 治疗的潜在药物。但PDGF-BB对神经元细胞的保护作用,尤其是分子机制尚不清楚,需要在临床应用前进一步探索。在这项研究中,我们研究了 PDGF-BB 对SH-SY5Y 细胞中 1-甲基-4-苯基吡啶 (MPP + ) 毒性的功能和机制,SH-SY5Y 细胞是一种广泛用于 PD 相关分子研究的细胞工具。我们的结果表明 PDGF-BB 对神经毒素 MPP +发挥显着的保护作用- 触发 ROS 生成和细胞丢失。我们通过使用特定的药理学抑制剂进一步剖析了该过程中涉及的分子机制,并验证了不同的信号通路 PI3K/Akt/GSK-3β 和 MEK/ERK 参与了对抗 MPP + PDGF-BB 治疗毒性的过程。我们还检测到上游 PI3K/Akt/GSK-3β 和 MER/ERK 信号通路的激活有助于下游效应器循环反应元件结合蛋白 (CREB) 的磷酸化和核易位,CREB ​​是一种具有神经保护和生长作用的已知转录因子。促进作用。使用遗传方法,我们进一步证实 CREB ​​的激活参与了 MPP +中 PDGF-BB 介导的保护- 暴露的 SH-SY5Y 细胞。总之,这些数据证明了 PDGF-BB 在 MPP +介导的 SH-SY5Y 细胞毒性中的保护作用,并验证了 PDGF-BB 介导的神经保护中涉及的分子机制。

更新日期:2020-11-09
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