Effects of Oxypeucedanin on Global Gene Expression and MAPK Signaling Pathway in Mouse Neuroblastoma Neuro-2A Cells

Abstract

Oxypeucedanin is a major coumarin aglycone that can be extracted from Ostericum koreanum. Coumarin aglycones have demonstrated various pharmacological effects, including anti-proliferation, anti-inflammation, and anti-pain. In this study, in order to understand the pharmacological properties of oxypeucedanin, we investigated global gene expression alteration in mouse neuroblastoma Neuro-2A cells. Results from the MTT assay indicated no decrease of cell viability up to 100 mu M for 24 h. We measured gene expression profiles in Neuro-2A cells treated with either 10 mu M or no oxypeucedanin for 24 h. We selected 128 differentially expressed genes (DEGs) for comparison of gene expression profiles by Bonferroni-adjusted p values (p < 0.1). Analysis of Gene Ontology (GO) biological process terms using the DEGs demonstrated the importance of protein metabolism, particularly ribosomal protein synthesis and protein degradation, intramembrane protein trafficking, and electron transport. Treatment with oxypeucedanin resulted in the downregulation of most DEGs for ribosomal protein synthesis and the electron transport chain (ETC). In contrast, most DEGs for protein degradation and cellular trafficking systems were upregulated. In addition, we found five upregulated DEGs for core and regulatory proteins involved in the mitogen-activated protein kinase (MAPK) signaling pathway. Independent translational validation of DEGs for MAPK signaling by immunoblot analysis showed consistent agreement with microarray data. Overall protein levels of Erk2 and p38MAPK were elevated, and their phosphorylated forms were also increased. These functional categories, based on transcriptional alteration and complicated modulation of MAPK signaling, might be underlying mechanisms responsible for the various pharmacological effects of oxypeucedanin.