Enhanced expression of WD repeat-containing protein 35 (WDR35) stimulated by domoic acid in rat hippocampus: involvement of reactive oxygen species generation and p38 mitogen-activated protein kinase activation

摘要: Background: Domoic acid (DA) is an excitatory amino analogue of kainic (KA) that acts via activation glutamate receptors to elicit a rapid and potent excitotoxic response, resulting in neuronal cell death. Recently, DA was shown reactive oxygen species (ROS) production induce apoptosis accompanied by p38 mitogen-activated protein kinase (MAPK) vitro. We have reported WDR35, WD-repeat protein, may mediate several animal models. In the present study, we administered rats intraperitoneally, then used liquid chromatography/ion trap tandem mass spectrometry (LC-MS/MS) identify quantify brains performed histological examinations hippocampus. further investigated potential involvement receptors, ROS, MAPK, WDR35 DA-induced toxicity vivo. Results: Our results showed intraperitoneally brain induced neurodegenerative changes including CA1 region also increased expression mRNA dose- time-dependent manner experiments using receptor antagonists, AMPA/KA antagonist NBQX significantly attenuated increase expression, but NMDA MK-801 did not. addition, radical scavenger edaravone expression. Furthermore, MAPK phosphorylation. Conclusion: summary, our indicated activated ROS phosphorylation,