Docosahexaenoic acid domains: the ultimate non-raft membrane domain

Wassall, Stephen R.; Stillwell, William

doi:10.1016/j.chemphyslip.2008.02.010

Cited by 191 publications

(171 citation statements)

References 67 publications

(104 reference statements)

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“…With 22 carbons and 6 double bonds, docosahexaenoic acid (DHA) is the most unsaturated PUFA commonly found in biological membranes [46] and so would be an ideal candidate for a-tocopherol association studies. We [47][48][49], as do others [50,51], attribute the efficacy of DHA in preventing numerous human afflictions in part to the formation of DHA-rich, non-raft domains from which cholesterol is excluded. The tremendous disorder of PUFA chains is responsible for the aversion cholesterol has for DHA-containing phospholipids [48,49].…”

Section: Pufa's Aversion To Cholesterolmentioning

confidence: 99%

“…We [47][48][49], as do others [50,51], attribute the efficacy of DHA in preventing numerous human afflictions in part to the formation of DHA-rich, non-raft domains from which cholesterol is excluded. The tremendous disorder of PUFA chains is responsible for the aversion cholesterol has for DHA-containing phospholipids [48,49]. Near approach of the steroid moiety is deterred by the wide variety of rapidly varying conformers that the DHA chain adopts.…”

Section: Pufa's Aversion To Cholesterolmentioning

confidence: 99%

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The location and behavior of α‐tocopherol in membranes

Atkinson

Harroun

Wassall

et al. 2010

Molecular Nutrition Food Res

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173

128

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Vitamin E (a-tocopherol) has long been recognized as the major antioxidant in biological membranes, and yet many structurally related questions persist of how the vitamin functions. For example, the very low levels of a-tocopherol reported for whole cell extracts question how this molecule can successfully protect the comparatively enormous quantities of PUFAcontaining phospholipids found in membranes that are highly susceptible to oxidative attack. The contemporary realization that membranes laterally segregate into regions of distinct lipid composition (domains), we propose, provides the answer. We hypothesize a-tocopherol partitions into domains that are enriched in polyunsaturated phospholipids, amplifying the concentration of the vitamin in the place where it is most needed. These highly disordered domains depleted in cholesterol are analogous, but organizationally antithetical, to the wellstudied lipid rafts. We review here the ideas that led to our hypothesis. Experimental evidence in support of the formation of PUFA-rich domains in model membranes is presented, focusing upon docosahexaenoic acid that is the most unsaturated fatty acid commonly found. Physical methodologies are then described to elucidate the nature of the interaction of a-tocopherol with PUFA and to establish that the vitamin and PUFA-containing phospholipids co-localize in non-raft domains.

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Section: Pufa's Aversion To Cholesterolmentioning

confidence: 99%

Section: Pufa's Aversion To Cholesterolmentioning

confidence: 99%

The location and behavior of α‐tocopherol in membranes

Atkinson

Harroun

Wassall

et al. 2010

Molecular Nutrition Food Res

Self Cite

173

128

View full text Add to dashboard Cite

show abstract

“…These characteristics mean that DHA can modulate the structure of specific membrane microdomains (lipid rafts and caveolae) and cell membrane functions. This includes the activity of membrane transporters, receptors and associated signalling pathways, and consequently affects cell behaviour 24 .…”

Section: Synthesis and Metabolism Of Dhamentioning

confidence: 99%

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

Skender¹,

Vaculová²,

Hofmanová³

2012

BIOMED PAP

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Background. Experimental, epidemiological and clinical data substantiate the beneficial role of n-3 polyunsaturated fatty acids (PUFAs) in preventing inflammation and cancer of the colon. This review covers the unsaturated docosahexaenoic fatty acid (DHA), describes some of its important cellular and molecular mechanisms, its interaction with another dietary lipid, butyrate and with endogenous apoptotic regulators of the tumour necrosis factor (TNF) family. We also discuss the clinical impact of this knowledge and the use of these lipids in colon cancer prevention and treatment. Results. From the literature, DHA has been shown to suppress the growth, induce apoptosis in colon cancer cells in vitro and decrease the incidence and growth of experimental tumours in vivo. Based on these data and our own experimental results, we describe and discuss the possible mechanisms of DHA anticancer effects at various levels of cell organization. We show that DHA can sensitize colon cancer cells to other chemotherapeutic/chemopreventive agents and affect the action of physiological apoptotic regulators of the TNF family. Conclusion. Use of n-3 PUFAs could be a relatively non-toxic form of supportive therapy for improving colon cancer treatment and slowing down or preventing its recurrence. However, it is necessary to use them with caution, based on solid scientific evidence of their mechanisms of action from the molecular to the cellular and organism levels.

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“…An increase in the proportion of unsaturated fatty acids therefore results in a weakening in the intermolecular hydrophobic interactions (Stillwell & Wassall, 2003). In this way basal properties of biological membranes are modulated including the assembly of the acyl chains, the fluidity, permeability and compressibility of the membrane, melting and flip-flop mechanisms as well as the function of membrane proteins (Stillwell & Wassall, 2003;Wassall & Stillwell, 2008).…”

Section: Cellular Membranesmentioning

confidence: 99%

The Impact of Macrophage Membrane Lipid Composition on Innate Immune Response Mechanisms

Schümann¹

2012

Inflammation, Chronic Diseases and Cancer - Cell and Molecular Biology, Immunology and Clinical Bases

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Docosahexaenoic acid domains: the ultimate non-raft membrane domain

Cited by 191 publications

References 67 publications

The location and behavior of α‐tocopherol in membranes

The location and behavior of α‐tocopherol in membranes

Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

The Impact of Macrophage Membrane Lipid Composition on Innate Immune Response Mechanisms

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