title: Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid.
abstract: BACKGROUND
  Maleic acid is a multi-functional chemical widely used in the field of industrial chemistry for producing food additives and food contact materials. As maleic acid may contaminate food by the release from food packages or intentional addition, it raises the concern about the effects of excessive dietary exposure to maleic acid on human health. However, the influence of maleic acid on human health has not been thoroughly studied. In silico toxicogenomics approaches have found the association between maleic acid and nervous system disease in human. The aim of this study is to experimentally explore the effects of maleic acid on human neuronal cells.
  
  
  METHODS
  A microarray-based transcriptome profiling was performed to offer a better understanding of the effects of maleic acid on human health. Gene expression profiles of human neuroblastoma SH-SY5Y cells exposed to three concentrations of maleic acid (10, 50, and 100 μM) for 24 h were analyzed. Genes which were differentially expressed in dose-dependent manners were identified and further analyzed with an enrichment analysis. The expression profile of selected genes related to the inferred functional changes was validated using quantitative polymerase chain reaction (qPCR). Specific fluorescence probes were applied to observe the inferred functional changes in maleic acid-treated neuronal cells.
  
  
  RESULTS
  A total of 316 differentially expressed genes (141 upregulated and 175 downregulated) were identified in response to the treatment of maleic acid. The enrichment analysis showed that DNA binding and metal ion binding were the significant molecular functions (MFs) of the neuronal cells affected by maleic acid. Maleic acid exposure decreased the expression of genes associated with calcium and thiol levels of the cells in a dose-dependent manner. The levels of intracellular calcium and thiol levels were also affected by maleic acid dose-dependent.
  
  
  CONCLUSIONS
  The exposure to maleic acid is found to decrease the cellular calcium and thiol levels in human neuronal cells at both transcriptional and functional levels. This study reported the first transcriptomic profiling of human neuronal cells treated with maleic acid. It is also the first experimental validation of chemical effects predicted by in silico toxicogenomics approaches. The proposed approach may be useful in understanding the potential effects of other poorly characterized chemicals on human health.
authors.affiliation: Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan; National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan; Institute of Environmental Engineering, National Sun Yat-sen University, Kaohsiung City, Taiwan.
authors.forename: Chia-Chi
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Yin-Chi
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University , Kaohsiung City , Taiwan.
authors.forename: Yin-Hua
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan; National Institute of Environmental Health Sciences, National Health Research Institutes, Miaoli County, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, Taiwan; Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
authors.forename: Chun-Wei
authors.identifier: 0000-0003-3011-8440
authors.initials: CW
authors.lastname: Tung
keywords: Deferentially expressed gene; Intracellular calcium; Maleic acid; Toxicogenomics; Transcriptome