Neuronal Specific Increase of Phosphatidylserine by Docosahexaenoic Acid

Chen, Guofang; Stockert, Lyubov; Akbar, Mohammed; Kim, Hee‐Yong

doi:10.1007/s12031-007-0046-z

Cited by 38 publications

(23 citation statements)

References 34 publications

(28 reference statements)

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“…Only the cells enriched with DHA in a serine depleted condition showed inhibited PS accumulation in agreement with the serine requirement for the mammalian PS synthesis using the serine-base exchange reaction. Similarly, over-expressing pss1 and pss2 genes cloned from the liver (Stone and Vance, 1999;Sturbois-Balcerzak et al, 2001) in non-neuronal cells did not increase the PS accumulation (Guo et al, 2007). These data suggest that PS levels are tightly regulated in living cells and these highly unsaturated very long chain fatty acids are uniquely capable of expanding the PS pool specifically in neuronal cells.…”

Section: Regulation Of Phosphatidylserine Accumulation In Cultured Cellsmentioning

confidence: 77%

“…Consistent with the brain microsomal PS biosynthetic activity shown above, DHA was more effective in accumulating PS in comparison to DPAn6. Non-neuronal cell lines including CHO-K1, NIH-3T3, HEK-293 and HELA did not increase total PS in response to DHA or DPAn6, suggesting that the phospholipid profile is differently regulated in neuronal cells (Guo et al, 2007). The molecular species analysis by electrospray HPLC/MS indicated that DHA was incorporated into PS mainly as 18:0,22:6 species also in non-neuronal cells.…”

Section: Regulation Of Phosphatidylserine Accumulation In Cultured Cellsmentioning

confidence: 91%

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Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol

Kim

2008

Chemistry and Physics of Lipids

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Docosahexaenoic acid (DHA, 22:6n-3), an n-3 fatty acid highly concentrated in the central nervous system, is essential for proper neuronal and retinal function. While a high level of DHA is generally maintained in neuronal membranes, inadequate supply of n-3 fatty acid or ethanol exposure leads to a significant loss of DHA in neuronal cells. The roles of DHA in neuronal signaling have been emerging. In this review, biological, biochemical and molecular mechanisms supporting the essential function of DHA in neuronal survival and development are described in relation to n-3 fatty acid depleting conditions.

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Section: Regulation Of Phosphatidylserine Accumulation In Cultured Cellsmentioning

confidence: 77%

Section: Regulation Of Phosphatidylserine Accumulation In Cultured Cellsmentioning

confidence: 91%

Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol

Kim

2008

Chemistry and Physics of Lipids

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“…Consistently, hippocampal neurons from DHA-depleted animals showed reduced amounts of PS and were more susceptible to cell death. As opposed to the findings with Neuro 2A cells, DHA supplementation did not increase the PS content in Chinese hamster ovary-K1 cells, NIH3T3 cells or HEK cells, suggesting that the PS increase induced by DHA occurs primarily in neuronal cells [180]. The protective action of DHA did not occur when Neuro 2A cells were incubated in a serine-free medium, suggesting that this effect is PS-dependent [2,4].…”

Section: Interactions Between Phosphatidylserine and Docosahexaenomentioning

confidence: 82%

Phosphatidylserine in the brain: Metabolism and function

Kim

Huang

Spector

2014

Progress in Lipid Research

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180

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Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine in reactions are catalyzed by phosphatidylserine synthase 1 and phosphatidylserine synthase 2 located in the endoplasmic reticulum. Activation of Akt, Raf-1 and protein kinase C signaling, which supports neuronal survival and differentiation, requires interaction of these proteins with PS localized in the cytoplasmic leaflet of the plasma membrane. Furthermore, neurotransmitter release by exocytosis and a number of synaptic receptors and proteins are modulated by PS present in the neuronal membranes. Brain is highly enriched with docosahexaenoic acid (DHA), and brain PS has a high DHA content. By promoting PS synthesis, DHA can uniquely expand the PS pool in neuronal membranes and thereby influence PS-dependent signaling and protein function. Ethanol decreases DHA-promoted PS synthesis and accumulation in neurons, which may contribute to the deleterious effects of ethanol intake. Improvement of some memory functions has been observed in cognitively impaired subjects as a result of PS supplementation, but the mechanism is unclear.

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“…DHA increases phosphatidylserine (PS) in neuronal cells and in turn translocates AKT from the cytosol to the membrane after ischemia; a required step for phosphorylation and activation of AKT [17], [18]. Here we have explored downstream AKT phosphorylation events.…”

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic Acid Signaling Modulates Cell Survival in Experimental Ischemic Stroke Penumbra and Initiates Long-Term Repair in Young and Aged Rats

Eady¹,

Belayev²,

Khoutorova³

et al. 2012

PLoS ONE

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BackgroundDocosahexaenoic acid, a major omega-3 essential fatty acid family member, improves behavioral deficit and reduces infarct volume and edema after experimental focal cerebral ischemia. We hypothesize that DHA elicits neuroprotection by inducing AKT/p70S6K phosphorylation, which in turn leads to cell survival and protects against ischemic stroke in young and aged rats.Methods and ResultsRats underwent 2 h of middle cerebral artery occlusion (MCAo). DHA, neuroprotectin D1 (NPD1) or vehicle (saline) was administered 3 h after onset of stroke. Neurological function was evaluated on days 1, 2, 3, and 7. DHA treatment improved functional recovery and reduced cortical, subcortical and total infarct volumes 7 days after stroke. DHA also reduced microglia infiltration and increased the number of astrocytes and neurons when compared to vehicle on days 1 and 7. Increases in p473 AKT and p308 AKT phosphorylation/activation were observed in animals treated with DHA 4 h after MCAo. Activation of other members of the AKT signaling pathway were also observed in DHA treated animals including increases in pS6 at 4 h and pGSK at 24 h. DHA or NPD1 remarkably reduced total and cortical infarct in aged rats. Moreover, we show that in young and aged rats DHA treatment after MCAo potentiates NPD1 biosynthesis. The phosphorylation of p308 AKT or pGSK was not different between groups in aged rats. However, pS6 expression was increased with DHA or NPD1 treatment when compared to vehicle.ConclusionsWe suggest that DHA induces cell survival, modulates the neuroinflammatory response and triggers long term restoration of synaptic circuits. Both DHA and NPD1 elicited remarkable protection in aged animals. Accordingly, activation of DHA signaling might provide benefits in the management of ischemic stroke both acutely as well as long term to limit ensuing disabilities.

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Neuronal Specific Increase of Phosphatidylserine by Docosahexaenoic Acid

Cited by 38 publications

References 34 publications

Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol

Biochemical and biological functions of docosahexaenoic acid in the nervous system: modulation by ethanol

Phosphatidylserine in the brain: Metabolism and function

Docosahexaenoic Acid Signaling Modulates Cell Survival in Experimental Ischemic Stroke Penumbra and Initiates Long-Term Repair in Young and Aged Rats

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