Abstract
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.
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Funding
Grants 81601125, 31601137, and 81673338 from National Natural Science Foundation of China, the Central University Basic Scientific Research Business Expenses Special Funds (grand number: A03019023801206 and ZYGX2017KYQD169), supported this work.
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LY and WZY contributed to research concept, research administration, and support. CH and TY carried out the experiments with the help of LZH, GF, and CXM. CH and TY performed statistical analyses. YJ, ZM, and JHS edited the manuscript. LY analyzed the data and wrote the manuscript. All authors edited and approved the final version of the manuscript.
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* Huan Chen, Yan Teng contributed equally to this work.
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Chen, H., Teng, Y., Liu, Z. et al. Molecular Mechanism of Platelet-Derived Growth Factor (PDGF)-BB-Mediated Protection Against MPP+ Toxicity in SH-SY5Y Cells. J Mol Neurosci 71, 1131–1143 (2021). https://doi.org/10.1007/s12031-020-01735-0
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DOI: https://doi.org/10.1007/s12031-020-01735-0