Reprod. Nutr. Dev.
Volume 45, Number 5, September-October 2005
|Page(s)||559 - 579|
Docosahexaenoic acid affects cell signaling by altering lipid raftsWilliam Stillwella, Saame Raza Shaikha, Mustafa Zerougab, Rafat Siddiquib and Stephen R. Wassallc
a Department of Biology, Indiana University - Purdue University Indianapolis, 723 West Michigan, Indianapolis, IN 46202, USA
b Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health Partners, 1801 N. Capitol Ave, Indianapolis, IN 46206, USA
c Department of Physics, Indiana University - Purdue University Indianapolis, 402 North Blackford St., Indianapolis, IN 46202, USA
(Received 3 January 2005; accepted 2 February 2005)
Abstract - With 22 carbons and 6 double bonds docosahexaenoic acid (DHA) is the longest and most unsaturated fatty acid commonly found in membranes. It represents the extreme example of a class of important human health promoting agents known as omega-3 fatty acids. DHA is particularly abundant in retinal and brain tissue, often comprising about 50% of the membrane's total acyl chains. Inadequate amounts of DHA have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities to depression and suicide. The molecular mode of action of DHA, while not yet understood, has been the focus of our research. Here we briefly summarize how DHA affects membrane physical properties with an emphasis on membrane signaling domains known as rafts. We report the uptake of DHA into brain phosphatidylethanolamines and the subsequent exclusion of cholesterol from the DHA-rich membranes. We also demonstrate that DHA-induced apoptosis in MDA-MB-231 breast cancer cells is associated with externalization of phosphatidylserine and membrane disruption ("blebbing"). We conclude with a proposal of how DHA incorporation into membranes may control cell biochemistry and physiology.
Key words: apoptosis / docosahexaenoic acid / lipid rafts / membranes / phospholipids
Corresponding author: William Stillwell firstname.lastname@example.org
© INRA, EDP Sciences 2005