The omega-3 fatty acid, DHA, decreases neuronal cell death in association with altered zinc transport

Suphioglu, Cenk; De Mel, Damitha; Kumar, Loveleen; Sadli, Nadia; Freestone, David; Michalczyk, Agnes; Sinclair, Andrew; Ackland, M. Leigh

doi:10.1016/j.febslet.2009.12.013

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Volume 584, Issue 3 , Pages 612-618, 5 February 2010

The omega-3 fatty acid, DHA, decreases neuronal cell death in association with altered zinc transport

Edited by Jesus Avila

Cenk Suphioglu
- School of Life and Environmental Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
- Corresponding author. Address: School of Life and Environmental Sciences, Faculty of Science and Technology, 221 Burwood Highway, Burwood, VIC 3125, Australia. Fax: +61 3 9251 7328.
Damitha De Mel
- School of Life and Environmental Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
Loveleen Kumar
- School of Life and Environmental Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
Nadia Sadli
- School of Life and Environmental Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
David Freestone
- School of Life and Environmental Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
Agnes Michalczyk
- School of Life and Environmental Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
Andrew Sinclair
- School of Exercise and Nutrition Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
- School of Medicine, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia
M. Leigh Ackland
- School of Life and Environmental Sciences, Deakin University, 221 Burwood Highway, Burwood, VIC 3125, Australia

Received 26 October 2009; received in revised form 4 December 2009; accepted 9 December 2009. published online 14 December 2009.

Abstract

Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid in neuronal cell membranes. We hypothesize that DHA induces a decrease in neuronal cell death through reduced ZnT3 expression and zinc uptake. Exposure of M17 cells to DHA-deficient medium increased the levels of active caspase-3, relative to levels in DHA-replete cells, confirming the adverse effects of DHA deficiency in promoting neuronal cell death. In DHA-treated M17 cells, zinc uptake was 65% less and ZnT3 mRNA and protein levels were reduced in comparison with DHA-depleted cells. We propose that the neuroprotective function of DHA is exerted through a reduction in cellular zinc levels that in turn inhibits apoptosis.

Keywords: DHA, Omega-3 fatty acid, Zinc, ZnT3, M17 human neuronal cell, Apoptosis