Neurotoxin-induced pathway perturbation in human neuroblastoma SH-EP cells.

摘要: The exact causes of cell death in Parkinson’s disease (PD) remain unknown despite extensive studies on PD.The identification signaling and metabolic pathways involved PD might provide insight into the molecular mechanisms underlying PD. neurotoxin 1-methyl-4-phenylpyridinium (MPP+) induces cellular changes characteristic PD, MPP+-based models have been extensively used for studies. In this study, that were significantly perturbed MPP+-treated human neuroblastoma SH-EP cells identified from genome-wide gene expression data five time points (1.5, 3, 9, 12, 24 h) after treatment. mitogen-activated protein kinase (MAPK) pathway endoplasmic reticulum (ER) processing showed significant perturbation at all points. Perturbation each these resulted common outcome upregulation DNA-damage-inducible transcript 3 (DDIT3). Genes ER included ubiquitin ligase complex genes ER-associated degradation (ERAD)-related genes. Additionally, overexpression DDIT3 induce oxidative stress via glutathione depletion as a result CHAC1. This study suggests caused by MAPK play key role MPP+-induced neuronal death. Moreover, toxicity signal MPP+ resulting mitochondrial dysfunction through inhibition I electron transport chain feed back to mitochondria stress. positive feedback could contribute amplification induced MPP+.