Docosahexaenoic acid: one molecule diverse functions

Hashimoto, Michio; Hossain, Shahdat; Mamun, Abdullah Al; Matsuzaki, Kei; Arai, Hiroyuki

doi:10.1080/07388551.2016.1207153

Cited by 134 publications

(115 citation statements)

References 145 publications

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“…DHA deficiency occurs during aging and dementia, impairs memory and learning, and promotes age-related neurodegenerative diseases, including Alzheimer’s disease. DHA is reported to have the ability of tumor inhibition and chemoprevention against colon cancer, prostate cancer, pancreatic cancer, and breast cancer [34]. EPA can compete with AA, an omega-6 PUFA, through the same metabolic pathways, but it produces eicosanoids that are functionally different from the AA derivatives.…”

Section: Fatty Acids Of Fish Oilmentioning

confidence: 99%

Cosmetic and Therapeutic Applications of Fish Oil’s Fatty Acids on the Skin

et al. 2018

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Fish oil has been broadly reported as a potential supplement to ameliorate the severity of some skin disorders such as photoaging, skin cancer, allergy, dermatitis, cutaneous wounds, and melanogenesis. There has been increasing interest in the relationship of fish oil with skin protection and homeostasis, especially with respect to the omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). The other PUFAs, such as α-linolenic acid (ALA) and linoleic acid (LA), also show a beneficial effect on the skin. The major mechanisms of PUFAs for attenuating cutaneous inflammation are the competition with the inflammatory arachidonic acid and the inhibition of proinflammatory eicosanoid production. On the other hand, PUFAs in fish oil can be the regulators that affect the synthesis and activity of cytokines for promoting wound healing. A systemic review was conducted to demonstrate the association between fish oil supplementation and the benefits to the skin. The following describes the different cosmetic and therapeutic approaches using fatty acids derived from fish oil, especially ALA, LA, DHA, and EPA. This review summarizes the cutaneous application of fish oil and the related fatty acids in the cell-based, animal-based, and clinical models. The research data relating to fish oil treatment of skin disorders suggest a way forward for generating advances in cosmetic and dermatological uses.

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Section: Fatty Acids Of Fish Oilmentioning

confidence: 99%

Cosmetic and Therapeutic Applications of Fish Oil’s Fatty Acids on the Skin

et al. 2018

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“…DHA is a major polyunsaturated fatty acid (PUFA) in the brain and is found in high concentrations (up to 50 mol% of the total acyl chains of phospholipids) in synaptic plasma membranes. Reduced levels are linked with impaired learning ability (Hashimoto et al, 2016; Janssen and Kiliaan, 2014). DHA is readily esterified and incorporated into membrane phospholipids, altering both the physical properties of the membrane and the expression and function of associated membrane proteins.…”

Section: Introductionmentioning

confidence: 99%

Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel

Basak

Schmandt

Gicheru

et al. 2017

eLife

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Desensitization in pentameric ligand-gated ion channels plays an important role in regulating neuronal excitability. Here, we show that docosahexaenoic acid (DHA), a key ω−3 polyunsaturated fatty acid in synaptic membranes, enhances the agonist-induced transition to the desensitized state in the prokaryotic channel GLIC. We determined a 3.25 Å crystal structure of the GLIC-DHA complex in a potentially desensitized conformation. The DHA molecule is bound at the channel-periphery near the M4 helix and exerts a long-range allosteric effect on the pore across domain-interfaces. In this previously unobserved conformation, the extracellular-half of the pore-lining M2 is splayed open, reminiscent of the open conformation, while the intracellular-half is constricted, leading to a loss of both water and permeant ions. These findings, in combination with spin-labeling/EPR spectroscopic measurements in reconstituted-membranes, provide novel mechanistic details of desensitization in pentameric channels.DOI: http://dx.doi.org/10.7554/eLife.23886.001

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“…DHA, a marine-derived nutraceutical, represents a promising lead compound for rational drug design and discovery. (1). For example, select ω-3 PUFAs may decrease cardiovascular disease risk (2).…”

mentioning

confidence: 99%

Atomic determinants of BK channel activation by polyunsaturated fatty acids

Tian

Aursnes

Hansen

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Docosahexaenoic acid (DHA), a polyunsaturated ω-3 fatty acid enriched in oily fish, contributes to better health by affecting multiple targets. Large-conductance Ca 2+ -and voltage-gated Slo1 BK channels are directly activated by nanomolar levels of DHA. We investigated DHA-channel interaction by manipulating both the fatty acid structure and the channel composition through the site-directed incorporation of unnatural amino acids. Electrophysiological measurements show that the para-group of a Tyr residue near the ion conduction pathway has a critical role. To robustly activate the channel, ionization must occur readily by a fatty acid for a good efficacy, and a long nonpolar acyl tail with a Z double bond present at the halfway position for a high affinity. The results suggest that DHA and the channel form an ion-dipole bond to promote opening and demonstrate the channel druggability. DHA, a marine-derived nutraceutical, represents a promising lead compound for rational drug design and discovery. -4,7,10,13,16,19-hexaenoic acid], found abundantly in oily fish, are believed to have many health-promoting effects (1). For example, select ω-3 PUFAs may decrease cardiovascular disease risk (2). Furthermore, human studies suggest that ω-3 PUFAs may lower blood pressure in some individuals (3). Thus, PUFAs such as DHA are natural nutraceuticals with great potential as lead compounds for rational drug design and discovery. To be successful, such an effort requires clear mechanistic understanding of the interactions between PUFAs and their effectors (4); however, the molecular targets of PUFAs and the mechanisms of action are only beginning to be revealed.One of the high-affinity targets of PUFAs is the large-conductance Ca 2+ -and voltage-gated K + (Slo1 BK) channel (5), whose activation in vascular smooth muscle cells facilitates vessel relaxation (6). Vascular Slo1 BK channels made of four pore-forming Slo1 and auxiliary β1 subunits (Slo1 + β1) are potently and reversibly activated by DHA with a nanomolar level of EC 50 , and this effect contributes to the hypotensive action of DHA in wild-type mice but not in mice with the gene encoding the channel (KCNMA1) disrupted (5).The function of the Slo1 BK channel can be electrophysiologically monitored with high precision to produce quantitative results amenable to mechanistic interpretations (7,8). Such in vitro studies show that DHA biases the ion conduction gate of the channel toward the open conformation without any need for activation of the channel's Ca 2+ sensors in the intracellular domain or transmembrane voltage sensor domains (VSDs) (5). Structurally, the action of DHA depends on a Tyr residue [Y318 in human Slo1 (hSlo1)] near the intracellular end of the ion conduction pathway; the mutation Y318S abolishes the activating effect of DHA (9).The exact role of Y318 in mediating the effect of DHA, however, is not clear. Some clues may be gained from interactions of other proteins with PUFAs. Extracellular DHA regulates voltagegated K + channels by interacting with ...

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Docosahexaenoic acid: one molecule diverse functions

Cited by 134 publications

References 145 publications

Cosmetic and Therapeutic Applications of Fish Oil’s Fatty Acids on the Skin

Cosmetic and Therapeutic Applications of Fish Oil’s Fatty Acids on the Skin

Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel

Atomic determinants of BK channel activation by polyunsaturated fatty acids

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