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Neuronal Specific Increase of Phosphatidylserine by Docosahexaenoic Acid

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Abstract

Phosphatidylserine (PS), the major acidic phospholipid class in eukaryotic biomembranes, plays an important role in various signaling pathways. We have previously demonstrated that docosahexaenoic acid (DHA, 22:6n-3) positively modulates PS biosynthesis and accumulation in neuronal cells, promoting survival. In this paper, we demonstrate that the increase of PS levels upon DHA enrichment is not a universal mechanism, but specific to neuronal cells. When cells were enriched with 20 μM DHA, 18:0, 22:6-PS increased in both neuronal (Neuro 2A) and non-neuronal cells (Chinese hamster ovary K1 cells, NIH-3T3, and human embryonic kidney cells). However, the increase of the total PS level was observed only in Neuro 2A cells because of the fact that other PS species, such as 18:0, 18:1-PS and 18:1, 18:1-PS decreased significantly in non-neuronal cells, compensating for the increase of 18:0, 22:6-PS. DHA enrichment did not affect the messenger RNA levels of PS synthase 1 (PSS1) and PSS2. Over-expression of genes encoding PSS1 or PSS2 altered neither the PS level nor the effect of DHA on PS increase in both neuronal and non-neuronal cells. From these results, it is concluded that the PS increase by DHA, specifically observed in neuronal cells, may represent a unique mechanism for expanding the PS pool so far known in mammalian cells.

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Abbreviations

CHO-K1 cells:

Chinese hamster ovary K1 cells

DHA:

docosahexaenoic acid

GC:

gas chromatography

HEK-293 cells:

human embryonic kidney cells

HPLC-ESI-MS:

high-performance liquid chromatography–electrospray ionization–mass spectrometry

Neuro 2A cells:

neuroblastoma cell

PC:

phosphatidylcholine

PE:

phosphatidylethanolamine

PS:

phosphatidylserine

PSS:

phosphatidylserine synthase

PUFA:

polyunsaturated fatty acids

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Acknowledgement

The authors thank Dr. J.E. Vance of University of Alberta for the generous gift of pss1 and pss2 plasmid used in this study. This study was supported by the intramural program, NIAAA, NIH.

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Authors and Affiliations

  1. Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Ln, Room 3N-07, Bethesda, MD, 20852-9410, USA

    Mingquan Guo, Lyubov Stockert, Mohammed Akbar & Hee-Yong Kim

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  1. Mingquan Guo
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  2. Lyubov Stockert
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  3. Mohammed Akbar
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  4. Hee-Yong Kim
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Correspondence to Hee-Yong Kim.

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Guo, M., Stockert, L., Akbar, M. et al. Neuronal Specific Increase of Phosphatidylserine by Docosahexaenoic Acid. J Mol Neurosci 33, 67–73 (2007). https://doi.org/10.1007/s12031-007-0046-z

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  • DOI: https://doi.org/10.1007/s12031-007-0046-z

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