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Zinc and DHA have opposing effects on the expression levels of histones H3 and H4 in human neuronal cells

Suphioglu, Cenk, Sadli, Nadia, Coonan, Damon, Kumar, Loveleen, De Mel, Damitha, Lesheim, Jessica, Sinclair, Andrew J. and Ackland, Leigh 2010, Zinc and DHA have opposing effects on the expression levels of histones H3 and H4 in human neuronal cells, British journal of nutrition, vol. 103, no. 3, pp. 344-351.

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Title Zinc and DHA have opposing effects on the expression levels of histones H3 and H4 in human neuronal cells
Author(s) Suphioglu, Cenk
Sadli, Nadia
Coonan, Damon
Kumar, Loveleen
De Mel, Damitha
Lesheim, Jessica
Sinclair, Andrew J.
Ackland, Leigh
Journal name British journal of nutrition
Volume number 103
Issue number 3
Start page 344
End page 351
Total pages 8
Publisher Cambridge University Press
Place of publication [Cambridge, England]
Publication date 2010-02-14
ISSN 0007-1145
1475-2662
Keyword(s) zinc
n-3 Fatty acids
DHA
M17 human neuronal cells
Histone H3
Histone H4
Summary Zn and DHA have putative neuroprotective effects and these two essential nutrients are known to interact biochemically. We aimed to identify novel protein candidates that are differentially expressed in human neuronal cell line M17 in response to Zn and DHA that would explain the molecular basis of this interaction. Two-dimensional gel electrophoresis and MS were applied to identify major protein expression changes in the protein lysates of human Ml7 neuronal cells that had been grown in the presence and absence of Zn and DHA. Proteomic findings were further investigated using Western immunoblot and real-time PCR analyses. Four protein spots, which had significant differential expression, were identified and selected for in-gel trypsin digestion followed by matrix-assisted laser desorption ionisation MS analysis. The resultant peptide mass fingerprint for each spot allowed their respective identities to be deduced. Two human histone variants H3 and H4 were identified. Both H3 and H4 were downregulated by Zn in the absence of DHA (Zn effect) and upregulated by DHA (DHA effect) in the presence of Zn (physiological condition). These proteomic findings were further supported by Western immunoblot and real-time PCR analyses using H3- and H4-specific monoclonal antibodies and oligonucleotide primers, respectively. We propose that dietary Zn and DHA cause a global effect on gene expression, which is mediated by histones. Such novel information provides possible clues to the molecular basis of neuroprotection by Zn and DHA that may contribute to the future treatment, prevention and management of neurodegenerative diseases such as Alzheimer's disease.
Language eng
Field of Research 111102 Dietetics and Nutrigenomics
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
HERDC collection year 2010
Copyright notice ©2009, The Authors
Persistent URL http://hdl.handle.net/10536/DRO/DU:30023162

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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.