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.

• Authors: Haejeong Park, Hakjae Kim, Eunyoung Ha, Seohyun Yoon, Mi-Ja Kim, Meesuk Hong, Kang-Hyun Leem, Seung-Jae Hong, Jongsoo Yang, Joo-Ho Chung
• Journal: Neurological research (Neurol Res) Vol. 29 Suppl 1 Pg. S78-87 ( 2007) ISSN: 0161-6412 [Print] England
• PMID: 17359646 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• IGF2BP3 protein, human
• Neoplasm Proteins
• Phosphoproteins
• Plant Preparations
• RNA-Binding Proteins
• SDCBP protein, human
• Syntenins
• Tetrazolium Salts
• Thiazoles
• KIF20B protein, human
• Kinesins
• thiazolyl blue

Topics

• Analysis of Variance
• Cell Cycle Proteins (metabolism)
• Cell Hypoxia (drug effects, physiology)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Down-Regulation (drug effects)
• Gene Expression Profiling (methods)
• Humans
• Kinesins
• Neoplasm Proteins (metabolism)
• Neuroblastoma
• Oligonucleotide Array Sequence Analysis (methods)
• Panax (chemistry)
• Phosphoproteins (metabolism)
• Plant Preparations (pharmacology)
• RNA-Binding Proteins (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Syntenins (metabolism)
• Tetrazolium Salts
• Thiazoles