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Synthesis and Identification of AceDoxyPC, a Protectin-Containing Structured Phospholipid, Using Liquid Chromatography/Mass Spectrometry

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Lipids

Abstract

Fatty acids have many health benefits in a great variety of diseases ranging from cardiovascular to cerebral diseases. For instance, docosahexaenoic acid (DHA), which is highly enriched in brain phospholipids, plays a major role in anti-inflammatory or neuroprotective pathways. Its effects are thought to be due, in part, to its conversion into derived mediators such as protectins. 1-Lyso,2-docosahexaenoyl-glycerophosphocholine (LysoPtdCho-DHA) is one of the physiological carrier of DHA to the brain. We previously synthesized a structured phosphatidylcholine to mimic 1-lyso,2-docosahexaenoyl-glycerophosphocholine, named AceDoPC® (1-acetyl,2-docosahexaenoyl-glycerophosphocholine), that is considered as a stabilized form of the physiological LysoPtdCho-DHA and that is neuroprotective in experimental ischemic stroke. Considering these, the current study aimed at enzymatically oxygenate DHA contained within AceDoPC® to synthesize a readily structured oxidized phospholipid containing protectin DX (PDX), thereafter named AceDoxyPC (1-acetyl,2-PDX-glycerophosphocholine). Identification of this product was performed using liquid chromatography/tandem mass spectrometry. Such molecule could be used as a bioactive mediator for therapy against neurodegenerative diseases and stroke.

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Abbreviations

AceDoPC:

1-Acetyl,2-DHA-glycerophosphocholine

AceDoxyPC:

1-Acetyl,2-PDX-glycerophosphocholine

BBB:

Blood–brain barrier

CID:

Collision-induced dissociation

DCC:

1,3-Dicyclohexylcarbodiimide

DMAP:

4-(Dimethylamino)pyridine

DMF:

Dimethylformamide

GPC:

sn-Glycerophosphocholine

LOX:

Lipoxygenase

LysoPtdCho-DHA:

1-Lyso,2-docosahexaenoyl-glycerophosphocholine

MRM:

Multiple reaction monitoring

PD1:

Protectin D1

PDX:

Protectin DX

sLOX:

Soybean lipoxygenase

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Acknowledgements

This study was supported by Lisa CARNOT Institute, National Institute of Applied Sciences-Lyon and the French Ministry of Education and Research. We thank Laurence Daniel and Valentin Ramel for their technical and supportive assistance.

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Authors and Affiliations

  1. Univ Lyon, INSA-Lyon, Inserm UMR 1060, Inra UMR 1397, CarMeN Laboratory, INSA, Bâtiment IMBL, 11 Avenue Jean Capelle, 69621, Villeurbanne Cedex, France

    Amanda Lo Van, Baptiste Fourmaux, Madeleine Picq, Michel Guichardant, Michel Lagarde & Nathalie Bernoud-Hubac

  2. Department of Developmental Neuroscience, Center for Neuroscience, ART, Tohoku University Graduate School of Medicine, Sendai, Japan

    Amanda Lo Van

Authors
  1. Amanda Lo Van
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  2. Baptiste Fourmaux
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  3. Madeleine Picq
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  6. Nathalie Bernoud-Hubac
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Correspondence to Nathalie Bernoud-Hubac.

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Conflict of interest

Pending patent: WO 2017006047 A1. NBH, MP, MG, and ML are associates in LipTher (http://www.lipther.com/), an emerging start up from the academic CarMeN laboratory, INSA-Lyon, whose objective is to produce AceDoPC® on a large scale.

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Lo Van, A., Fourmaux, B., Picq, M. et al. Synthesis and Identification of AceDoxyPC, a Protectin-Containing Structured Phospholipid, Using Liquid Chromatography/Mass Spectrometry. Lipids 52, 751–761 (2017). https://doi.org/10.1007/s11745-017-4280-z

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  • DOI: https://doi.org/10.1007/s11745-017-4280-z

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