1. [Fasudil reduces apoptosis of SH-SY5Y cells induced by H 2 O 2 and promotes synaptic plasticity by inhibiting neurite outgrowth inhibitor A and its receptor (NogoA/NgR) signaling pathway].
- Author
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Guo M, Zhang H, Yu J, Zhang P, Wang Y, Wei W, Song L, Chai Z, Yu J, and Ma C
- Subjects
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine analogs & derivatives, Apoptosis, Humans, Hydrogen Peroxide pharmacology, Neuronal Outgrowth, Neuronal Plasticity, Nogo Receptor 1, Receptor, Nerve Growth Factor, Signal Transduction, Neuroblastoma, Nogo Receptors
- Abstract
Objective To investigate the effect of Fasudil on H
2 O2 -induced apoptosis and synaptic plasticity in human neuroblastoma SY5Y cells and its mechanism. Methods The cells were divided into three groups: PBS control group, H2 O2 model group (250 μmol/L H2 O2 treatment) and Fasudil intervention group (250 μmol/L H2 O2 combined with 15 μg/mL Fasudil treatment). MTT assay was applied to detect cell activity and TUNEL was performed to detect cell apoptosis respectively. Immunofluorescence cytochemical staining was used to determine the expression of neurite outgrowth inhibitor A (NogoA), Nogo receptor (NgR) and synaptophysin (Syn). Western blotting was then conducted to detect the expression of NogoA, NgR, p75 neurotrophin receptor (p75NTR), leucine-rich repeat Ig domain-containing Nogo-interacting protein 1 (LINGO-1), Syn and postsynaptic density protein-95 (PSD-95). Results Compared with the PBS group, the H2 O2 group showed decreased cell viability and increased apoptosis rate while Fasudil treatment significantly increased the cell viability and reduced the apoptosis rate. Compared with the H2 O2 model group, Fasudil intervention increased expressions of Syn and PSD-95. Compared with the PBS group, the expression of NogoA and its receptor complex NgR/p75NTR/LINGO-1 grew significantly in the H2 O2 group, suggesting Fasudil treatment could inhibit the expression of NogoA and its receptor complex NgR/p75NTR/LINGO-1. Conclusion Fasudil may inhibit the activation of the NogoA/NgR signaling pathway, therefore reducing the apoptosis induced by H2 O2 in SH-SY5Y cells and enhancing the plasticity of the synapses.- Published
- 2022