Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid

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 ex...

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Main Authors: Chia-Chi Wang, Yin-Chi Lin, Yin-Hua Cheng, Chun-Wei Tung
Format: Article
Language:English
Published: PeerJ Inc. 2017-04-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/3175.pdf
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author Chia-Chi Wang
Yin-Chi Lin
Yin-Hua Cheng
Chun-Wei Tung
author_facet Chia-Chi Wang
Yin-Chi Lin
Yin-Hua Cheng
Chun-Wei Tung
author_sort Chia-Chi Wang
collection DOAJ
description 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. Discussion 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.
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spelling doaj.art-ea0e50cb769d4992b6b6d8534c7849442023-12-03T10:37:59ZengPeerJ Inc.PeerJ2167-83592017-04-015e317510.7717/peerj.3175Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acidChia-Chi Wang0Yin-Chi Lin1Yin-Hua Cheng2Chun-Wei Tung3Ph.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, TaiwanPh.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, TaiwanPh.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, TaiwanPh.D. Program in Toxicology, College of Pharmacy, Kaohsiung Medical University, Kaohsiung City, TaiwanBackground 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. Discussion 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.https://peerj.com/articles/3175.pdfMaleic acidToxicogenomicsDeferentially expressed geneIntracellular calciumTranscriptome
spellingShingle Chia-Chi Wang
Yin-Chi Lin
Yin-Hua Cheng
Chun-Wei Tung
Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid
PeerJ
Maleic acid
Toxicogenomics
Deferentially expressed gene
Intracellular calcium
Transcriptome
title Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid
title_full Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid
title_fullStr Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid
title_full_unstemmed Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid
title_short Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid
title_sort profiling transcriptomes of human sh sy5y neuroblastoma cells exposed to maleic acid
topic Maleic acid
Toxicogenomics
Deferentially expressed gene
Intracellular calcium
Transcriptome
url https://peerj.com/articles/3175.pdf
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