Genome-wide transcriptional comparison of MPP<sup>+</sup> treated human neuroblastoma cells with the state space model

Jin Hwan Do; Jin Hwan Do

doi:10.3934/molsci.2015.4.440

AIMS Molecular Science

2015, Volume 2, Issue 4: 440-460. doi: 10.3934/molsci.2015.4.440

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Genome-wide transcriptional comparison of MPP⁺ treated human neuroblastoma cells with the state space model

Jin Hwan Do ^,

Department of Biomolecular and Chemical Engineering, DongYang University, Yeongju 750-711, South Korea

Received: 24 August 2015 Accepted: 22 October 2015 Published: 26 October 2015

This study compared a parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺) response in two distinct phenotypes of human neuroblastoma cell lines: neuronal N-type SH-SY5Y cells and flat substrate-adherent S-type SH-EP cells. SH-SY5Y and SH-EP cells shared only 14% of their own MPP⁺ response genes, and their gene ontology (GO) analysis revealed significant endoplasmic reticulum (ER) stress by misfolded proteins. Gene modules, which are groups of transcriptionally co-expressed genes with similar biological functions, were identified for SH-SY5Y and SH-EP cells by using time-series microarray data with the state space model (SSM). All modules of SH-SY5Y and SH-EP cells showed strong positive auto-regulation that was often mediated via signal molecules and may cause bi-stability. Interactions in gene levels were calculated by using SSM parameters obtained in the process of module identification. Gene networks that were constructed from the gene interaction matrix showed different hub genes with high node degrees between SH-SY5Y and SH-EP cells. That is, key hub genes of SH-SY5Y cells were DCN, HIST1H2BK, and C5orf40, whereas those of SH-EP cells were MSH6, RBCK1, MTHFD2, ZNF26, CTH, and CARS. These results suggest that inhibition of the mitochondrial complex I by MPP⁺ might induce different downstream processes that are cell type dependent.
- neuroblastoma,
- 1-methyl-4-phenylpyridinium,
- cell death,
- Parkinson's disease,
- transcriptional regulation,
- gene networks,
- state space model
Citation: Jin Hwan Do. Genome-wide transcriptional comparison of MPP+ treated human neuroblastoma cells with the state space model[J]. AIMS Molecular Science, 2015, 2(4): 440-460. doi: 10.3934/molsci.2015.4.440

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Abstract

This study compared a parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP⁺) response in two distinct phenotypes of human neuroblastoma cell lines: neuronal N-type SH-SY5Y cells and flat substrate-adherent S-type SH-EP cells. SH-SY5Y and SH-EP cells shared only 14% of their own MPP⁺ response genes, and their gene ontology (GO) analysis revealed significant endoplasmic reticulum (ER) stress by misfolded proteins. Gene modules, which are groups of transcriptionally co-expressed genes with similar biological functions, were identified for SH-SY5Y and SH-EP cells by using time-series microarray data with the state space model (SSM). All modules of SH-SY5Y and SH-EP cells showed strong positive auto-regulation that was often mediated via signal molecules and may cause bi-stability. Interactions in gene levels were calculated by using SSM parameters obtained in the process of module identification. Gene networks that were constructed from the gene interaction matrix showed different hub genes with high node degrees between SH-SY5Y and SH-EP cells. That is, key hub genes of SH-SY5Y cells were DCN, HIST1H2BK, and C5orf40, whereas those of SH-EP cells were MSH6, RBCK1, MTHFD2, ZNF26, CTH, and CARS. These results suggest that inhibition of the mitochondrial complex I by MPP⁺ might induce different downstream processes that are cell type dependent.

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