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Malta, NY, United States

Phospholipidomics by high-performance liquid chromatography coupled to electrospray mass spectrometry or tandem mass spectrometry, including sample preparation, instrumental analyses, and data interpretation, is described in the chapter. © 2011 Springer Science+Business Media, LLC. Source

Chen S.,Chainon Neurotrophin Biotechnology Inc. | Belikova N.A.,University of Illinois at Chicago | Subbaiah P.V.,University of Illinois at Chicago
Analytica Chimica Acta | Year: 2012

Although marine oysters contain abundant amounts of ether-linked aminophospholipids, the structural identification of the various molecular species has not been reported. We developed a normal-phase silica liquid chromatography/negative-ion electrospray ionization/quadrupole multiple-stage linear ion-trap mass spectrometric (NPLC-NI-ESI/Q-TRAP-MS 3) method for the structural elucidation of ether molecular species of serine and ethanolamine phospholipids from marine oysters. The major advantages of the approach are (i) to avoid incorrect selection of isobaric precursor ions derived from different phospholipid classes in a lipid mixture, and to generate informative and clear MS n product ion mass spectra of the species for the identification of the sn-1 plasmanyl or plasmenyl linkages, and (ii) to increase precursor ion intensities by "concentrating" lipid molecules of each phospholipid class for further structural determination of minor molecular species. Employing a combination of NPLC-NI-ESI/MS 3 and NPLC-NI-ESI/MS 2, we elucidated, for the first time, the chemical structures of docosahexaenoyl and eicosapentaenoyl plasmenyl phosphatidylserine (PS) species and differentiated up to six isobaric species of diacyl/alkylacyl/alkenylacyl phosphatidylethanolamine (PE) in the US pacific oysters. The presence of a high content of both omega-3 plasmenyl PS/plasmenyl PE species and multiple isobaric molecular species isomers is the noteworthy characteristic of the marine oyster. The simple and robust NPLC-NI-ESI/MS n-based methodology should be particularly valuable in the detailed characterization of marine lipid dietary supplements with respect to omega-3 aminophospholipids. © 2012 Elsevier B.V. Source

Chen S.,Chainon Neurotrophin Biotechnology Inc. | Subbaiah P.V.,University of Illinois at Chicago
Lipids | Year: 2013

Because neurons cannot synthesize docosahexaenoic acid (DHA), a dietary supplement of DHA in the form of phospholipids is recommended for maintaining proper brain functions. A model for delivering dietary sn-2-DHA phosphatidylcholine (PtdCho) to the brain involves phospholipase A2 based deacylation/reacylation cycle followed by delivery of DHA through high-density lipoproteins that bind to the brain capillary endothelial cells in the blood-brain barrier (BBB). Our previous study demonstrated preference of endothelial lipase (EL) for PtdCho species that contain sn-2-DHA, resulting in production of sn-2-DHA lysoPtdCho that is preferentially taken up by the brain. However, since CoA-dependent reacylation of lysoPtdCho with DHA at the sn-2 position is not favored in vivo, we proposed that sn-1-DHA PtdCho in the diet may be a superior source of DHA for the brain. To test this hypothesis, DHA PtdCho regioisomers were prepared, and their hydrolysis by physiologically relevant phospholipases was determined. The data presented here show that: (1) group X secretory PLA2 (sPLA2) is about threefold more active than group V sPLA2 in releasing sn-2 fatty acids from DHA regioisomers, and (2) EL shows its specificity for DHA PtdCho species in a concentration independent manner, suggesting that the enzyme could play a major role in generating free sn-1-DHA or/and sn-2-DHA lysoPtdCho from the regioisomers in the BBB. We propose that PtdCho species containing sn-1-DHA may have the advantages of both "preserving" DHA in deacylation/ reacylation cycle and releasing free DHA in the BBB for uptake by the brain. © 2013 AOCS. Source

Chen S.,Chainon Neurotrophin Biotechnology Inc.
Recent Patents on CNS Drug Discovery | Year: 2010

The most common age-dependent neurodegenerative disorders such as dementia and Alzheimer's disease have become an urgent public health problem in the most areas of the world. The strategy of the current therapy focuses on increasing availability of brain acetylcholine concentration, and use of acetylcholinesterase inhibitors has become the main approach to symptomatic treatment. However, an ideal drug for the disorders should enable to both simultaneously delay or halt the underlying pathological process and improve memory. The present paper describes an alterative cholinergic strategy to memory enhancement by the exogenous introduction of highly enriched docosahexaenoic acid (DHA) - containing molecular species of highly pure phospholipids and highly pure ether phospholipids based brain DHA transporters to promote survival of aged basal forebrain cholinergic neurons (BFCNs) through reversing abnormal levels of neural membrane DHA aminophospholipids. This results in significantly improving neural membrane fluidity and gap capacity leading to further recovering the expression of the p75 neurotrophin receptor and then failed retrograde nerve growth factor signaling, followed by promoting the choline acetyltransferase activity in the BFCNs. The pre-clinical results shown in published patents and recent applications to support the proposed therapeutic mechanism of the brain DHA transporters are summarized. The advantage of the potential drugs in both the prevention and treatment of age-dependent basal forebrain cholinergic dysfunction related neurodegenerative disorders is further discussed. © 2010 Bentham Science Publishers Ltd. Source

Chen S.,Chainon Neurotrophin Biotechnology Inc. | Liu C.,Shanghai Ocean University
Current Organic Chemistry | Year: 2013

Ether glycerophospholipids (GPLs) are a subclass of phospholipids, chemically characterized by the existence of an ether bond within the lipid molecules. Because ether GPLs are membrane structure components, they act as the wide-like resistance to membrane oxidation induced by chemical hypoxia and reactive oxygen species. The abnormal biosynthesis of ether GPLs in humans leads to the decreased supply of the critical lipids to various human cells, resulting in the alteration of the membrane lipid composition. Recent studies demonstrated that the level of docosahexaenoic acid (DHA) - containing ether molecular species of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in the Alzheimer's brain significantly decreased. On the other hand, the deficiency of DHA and plateletactivating factor in human sperm causes infertility in men. We propose that the supplementation of DHA ether molecular species of GPLs may prevent and treat brain disorders, such as Alzheimer's disease and autism, and infertility. The present review describes (1) procedures for the semi-synthesis of DHA - containing ether molecular species of PC and PE; (2) mass spectrometric methods for structurally identifying the lipids; (3) potential of DHA plasmanycholine species as lipid drugs for preventing and treating brain diseases and infertility; and (4) recommendation of marine oysters, monkfish liver and scallops based seafoods as DHA ether GPLs supplementation for the medical application. © 2013 Bentham Science Publishers. Source

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