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Global DNA methylation profiling of manganese-exposed human neuroblastoma SH-SY5Y cells reveals epigenetic alterations in Parkinson’s disease-associated genes

Tarale, Prashant; Sivanesan, Saravanadevi; Daiwile, Atul P.; Stöger, Reinhard; Bafana, Amit; Naoghare, Pravin K.; Parmar, Devendra; Chakrabarti, Tapan; Kannan, Krishnamurthi

Authors

Prashant Tarale

Saravanadevi Sivanesan

Atul P. Daiwile

Amit Bafana

Pravin K. Naoghare

Devendra Parmar

Tapan Chakrabarti

Krishnamurthi Kannan



Abstract

Manganese (Mn) is an essential trace element required for optimal functioning of cellular biochemical pathways in the central nervous system. Elevated exposure to Mn through environmental and occupational exposure can cause neurotoxic effects resulting in manganism, a condition with clinical symptoms identical to idiopathic Parkinson’s disease. Epigenetics is now recognized as a biological mechanism involved in the etiology of various diseases. Here, we investigated the role of DNA methylation alterations induced by chronic Mn (100 µM) exposure in human neuroblastoma (SH-SY5Y) cells in relevance to Parkinson’s disease. A combined analysis of DNA methylation and gene expression data for Parkinson’s disease-associated genes was carried out. Whole-genome bisulfite conversion and sequencing indicate epigenetic perturbation of key genes involved in biological processes associated with neuronal cell health. Integration of DNA methylation data with gene expression reveals epigenetic alterations to PINK1, PARK2 and TH genes that play critical roles in the onset of Parkinsonism. The present study suggests that Mn-induced alteration of DNA methylation of PINK1–PARK2 may influence mitochondrial function and promote Parkinsonism. Our findings provide a basis to further explore and validate the epigenetic basis of Mn-induced neurotoxicity.

Citation

Tarale, P., Sivanesan, S., Daiwile, A. P., Stöger, R., Bafana, A., Naoghare, P. K., …Kannan, K. (2017). Global DNA methylation profiling of manganese-exposed human neuroblastoma SH-SY5Y cells reveals epigenetic alterations in Parkinson’s disease-associated genes. Archives of Toxicology, 91(7), 2629-2641. https://doi.org/10.1007/s00204-016-1899-0

Journal Article Type Article
Acceptance Date Nov 24, 2016
Online Publication Date Dec 2, 2016
Publication Date 2017-07
Deposit Date Dec 8, 2016
Publicly Available Date Dec 8, 2016
Journal Archives of Toxicology
Print ISSN 0340-5761
Electronic ISSN 1432-0738
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 91
Issue 7
Pages 2629-2641
DOI https://doi.org/10.1007/s00204-016-1899-0
Keywords DNA methylation, Manganese, Epigenetics, Parkinson’s disease, WGBS
Public URL http://eprints.nottingham.ac.uk/id/eprint/39241
Publisher URL http://dx.doi.org/10.1007/s00204-016-1899-0
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf
Additional Information The final publication is available at Springer via http://dx.doi.org/10.1007/s00204-016-1899-0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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