Synthesis and Identification of AceDoxyPC, a Protectin-Containing Structured Phospholipid, Using Liquid Chromatography/Mass Spectrometry
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.
KeywordsOmega-3 fatty acids Docosahexaenoic acid Lipoxygenase Mass spectrometry Protectin DX Structured phospholipid
Multiple reaction monitoring
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.
Compliance with Ethical Standards
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.
- 5.Brossard N, Croset M, Normand S, Pousin J, Lecerf J, Laville M, Tayot JL, Lagarde M (1997) Human plasma albumin transports [13C]docosahexaenoic acid in two lipid forms to blood cells. J Lipid Res 7:1571–1582Google Scholar
- 8.Wong BH, Chan JP, Cazenave-Gassiot A, Poh RW, Foo JC, Galam DL, Ghosh S, Nguyen LN, Barathi VA, Yeo SW, Luu CD, Wenk MR, Silver DL (2016) Mfsd2a is a transporter for the essential ω-3 fatty acid docosahexaenoic acid (DHA) in eye and is important for photoreceptor cell development. J Biol Chem 291:10501–10514CrossRefGoogle Scholar
- 18.Gonzalez-Periz A, Horrillo R, Ferre N, Gronert K, Dong B, Moran-Salvador E, Titos E, Martinez-Clemente M, Lopez-Parra M, Arroyo V, Claria J (2009) Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J 23:1946–1957CrossRefGoogle Scholar
- 19.Aveldano MI, Sprecher H (1983) Synthesis of hydroxy fatty acids from 4,7,10,13,16,19-[1-14C] docosahexaenoic acid by human platelets. J Biol Chem 25:9339–9343Google Scholar
- 27.Leitinger N, Tyner TR, Oslund L, Rizza C, Subbanagounder G, Lee H, Shih PT, Mackman N, Tigyi G, Territo MC, Berliner JA, Vora DK (1999) Structurally similar oxidized phospholipids differentially regulate endothelial binding of monocytes and neutrophils. Proc Natl Acad Sci USA 96:12010–12015CrossRefGoogle Scholar
- 33.Ashraf MZ, Srivastava S (2012) Oxidized phospholipids: introduction and biological significance. In: Frank S, Kostner G (eds) Lipoproteins – role health disease. InTech, Rijeka, pp 409–430Google Scholar