Panax ginseng increases hypoxia-induced down-regulated cellular response related genes in human neuroblastoma cells, SK-N-MC

Abstract

Background: Many studies have suggested that hypoxia plays a crucial role in the pathogenesis of various neurological disorders. To determine protective effect of Panax ginseng (PG) on hypoxia (0.1% O(2))-induced cell death in human neuroblastoma cells SK-N-MC, we profiled the gene expression among hypoxia, PG-treated hypoxia and normoxia groups.

Methods: To determine protective effect on hypoxia-induced cytotoxicity of PG, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We compared the gene expression profiles among hypoxia, PG-treated hypoxia (100 mug/ml, 6 hours) and normoxia groups using 8K human cDNA microarray analysis. Additionally, in order to identify differentially expressed genes between hypoxia and PG-treated hypoxia groups, hierarchical clustering of genes was also performed.

Results: MTT assay showed that PG protected hypoxia-induced cell death. In cDNA microarray analysis, hypoxia remarkably down-regulated IGF-II mRNA-binding protein 3 (IMP-3), integrin alpha 2 (ITGA2), syndecan binding protein (SDCBP), insulin-like growth factor binding protein 3 (IGBP3) and M-phase phosphoprotein 10 (MPHOSPH10), belonging to category of cellular physiologic response (global M<-3.5). In cluster analysis, 1428 genes exhibited differential expression levels between hypoxia and PG-treated hypoxia groups. Of them, the expressions of 11 genes were increased more than two-fold by PG treatment compared to those in hypoxia group. Particularly, of 11 genes, the expression levels of cellular physiologic response related genes such as MPHOSPH10, IMP-3 and SDCBP, which markedly down-regulated by hypoxia, are increased more than four-fold by PG treatment, compared to hypoxia group.

Conclusion: In summary, hypoxia induced down-regulation of cellular physiologic response related genes in human neuroblastoma cells, SK-N-MC, and PG ameliorated the hypoxia-induced down-regulation of such genes. These results indicate possible usage of PG in hypoxia-induced neuronal injury including ischemia, trauma and degenerative diseases.