Regulated expression of endothelial lipase by porcine brain capillary endothelial cells constituting the blood–brain barrier

Sovic, Andrea; Panzenboeck, Ute; Wintersperger, Andrea; Kratzer, Ingrid; Hammer, Astrid; Levak-Frank, Sanja; Frank, Saša; Rader, Daniel J.; Malle, Ernst; Sattler, Wolfgang

doi:10.1111/j.1471-4159.2005.03175.x

Cited by 37 publications

(31 citation statements)

References 68 publications

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“…Cardiomyocytes from CD36 -/-have a one-fold increase in fatty acid transport protein 1 (FATP1) which could be a compensatory mechanism in the absence of CD36 [63]. In addition, esterified PUFA might be cleaved from lipoproteins at the BBB by enzymes such as lipoprotein lipase [20] or endothelial lipase [64][65][66], thus providing another pool from which PUFA can enter the brain.…”

Section: Discussionmentioning

confidence: 98%

Genetic Ablation of CD36 Does not Alter Mouse Brain Polyunsaturated Fatty Acid Concentrations

Song

Elbert

Rahman

et al. 2010

Lipids

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In the brain, polyunsaturated fatty acids (PUFA), especially arachidonic acid and docosahexaenoic acid (DHA), are required for regulating membrane fluidity, neuronal survival and signal transduction. Since the brain cannot synthesize n-6 and n-3 PUFA de novo, they must be supplied from the blood. However, the methods of PUFA entry into the brain are not agreed upon. This study tested the necessity of CD36, a candidate transporter of unesterified fatty acids, for maintaining brain PUFA concentrations by comparing brain PUFA concentrations in CD36(-/-) mice to their wild-type littermates. Because CD36(-/-) mice have been reported to have impaired learning ability, the PUFA concentrations in different brain regions (cortex, hippocampus, cerebellum and the remainder of brain) were investigated. At 9 weeks of age, the brain was separated into the four regions and fatty acid concentrations in total and phospholipid classes of these brain regions were analyzed using thin layer and gas chromatography. There were no statistical differences in arachidonic acid or DHA concentrations in the different brain regions between wild-type and CD36(-/-) mice, in total or phospholipid fractions. Concentrations of monounsaturated fatty acids were decreased in several phospholipid fractions in CD36(-/-) mice. These findings suggest that CD36 is not necessary for maintaining brain PUFA concentrations and that other mechanisms must exist.

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Section: Discussionmentioning

confidence: 98%

Genetic Ablation of CD36 Does not Alter Mouse Brain Polyunsaturated Fatty Acid Concentrations

Song

Elbert

Rahman

et al. 2010

Lipids

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“…VLDL receptors are found on brain capillaries, but in vivo feeding and infusion studies indicate that long-chain fatty acids within plasma are largely taken up by brain in their unesterified form and not within lipoproteins (52,53). Thus, DHA within secreted VLDLs would first have to be hydrolyzed to unesterified DHA in adipose tissue, in the circulation, or at the blood-brain barrier by appropriate lipases before being incorporated into brain (54)(55)(56). With regard to unesterified circulating DHA, tracer injection studies suggest that z0.5% and z4.6% of the intravenously injected amount will be taken up by brain in adult rats and fetal baboons, respectively (57,58).…”

Section: Discussionmentioning

confidence: 99%

Upregulated liver conversion of α-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet

Igarashi

DeMar²,

et al. 2007

Journal of Lipid Research

102

138

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We quantified incorporation rates of plasmaderived a-linolenic acid (a-LNA, 18:3n-3) into "stable" liver lipids and the conversion rate of a-LNA to docosahexaenoic acid (DHA, 22:6n-3) in male rats fed, after weaning, an n-3 PUFA-adequate diet (4.6% a-LNA, no DHA) or an n-3 PUFAdeficient diet (0.2% a-LNA, no DHA) for 15 weeks. Unanesthetized rats were infused intravenously with [1-14 C]a-LNA, and arterial plasma was sampled until the liver was microwaved at 5 min. Unlabeled a-LNA and DHA concentrations in arterial plasma and liver were reduced .90% by deprivation, whereas unlabeled arachidonic acid (20:4n-6) and docosapentaenoic acid (22:5n-6) concentrations were increased. Deprivation did not change a-LNA incorporation coefficients into stable liver lipids but increased synthesis-incorporation coefficients of DHA from a-LNA by 6.6-, 8.4-, and 2.3-fold in triacylglycerol, phospholipid, and cholesteryl ester, repectively. Assuming that synthesized-incorporated DHA even tually would be secreted within lipoproteins, calculated liver DHA secretion rates equaled 2.19 and 0.82 mmol/day in the n-3 PUFA-adequate and -deprived rats, respectively. These rates exceed the published rates of brain DHA consumption by 6-and 10-fold, respectively, and should be sufficient to maintain normal and reduced brain DHA concentrations, respectively, in the two dietary conditions.-

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“…We verified that incubation of AceDoPC in the same medium without cells did not lead to degradation of the molecule (not shown). The formation of lysoPC-DHA might occur through the action of the endothelial lipase, a phospholipase A 1 (PLA 1 )-like enzyme that has been shown to be expressed and secreted in BCECs [30] and to have a preference for DHA-containing phospholipids at the sn-2 position [31]. However, no hydrolysis of PC-DHA has been observed in the upper medium after incubation of cells with PC-DHA.…”

Section: Discussionmentioning

confidence: 96%

Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid

et al. 2015

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Docosahexaenoic acid (DHA) is the main essential omega-3 fatty acid in brain tissues required for normal brain development and function. An alteration of brain DHA in neurodegenerative diseases such as Alzheimer's and Parkinson's is observed. Targeted intake of DHA to the brain could compensate for these deficiencies. Blood DHA is transported across the blood-brain barrier more efficiently when esterified at the sn-2 position of lyso-phosphatidylcholine. We used a structured phosphatidylcholine to mimic 2-docosahexaenoyl-lysoPC (lysoPC-DHA), named AceDoPC (1-acetyl,2-docosahexaenoyl-glycerophosphocholine), that may be considered as a stabilized form of the physiological lysoPC-DHA and that is neuroprotective in experimental ischemic stroke. The aim of the present study was to investigate whether AceDoPC is a relevant delivery form of DHA to the brain in comparison with other forms of the fatty acid. By combining in vitro and in vivo experiments, our findings report for the first time that AceDoPC is a privileged and specific carrier of DHA to the brain, when compared with DHA-containing PC and non-esterified DHA. We also show that AceDoPC was hydrolyzed, in part, into lysoPC-DHA. Ex vivo autoradiography of rat brain reveals that DHA from AceDoPC was localized in specific brain regions playing key roles in memory, thoughts, and cognitive functions. Finally, using molecular modeling approaches, we demonstrate that electrostatic and lipophilic potentials are distributed very similarly at the surfaces of AceDoPC and lysoPC-DHA. Our findings identify AceDoPC as an efficient way to specifically target DHA to the brain, which would allow potential preventive and therapeutic approaches for neurological diseases.

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Regulated expression of endothelial lipase by porcine brain capillary endothelial cells constituting the blood–brain barrier

Cited by 37 publications

References 68 publications

Genetic Ablation of CD36 Does not Alter Mouse Brain Polyunsaturated Fatty Acid Concentrations

Genetic Ablation of CD36 Does not Alter Mouse Brain Polyunsaturated Fatty Acid Concentrations

Upregulated liver conversion of α-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet

Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid

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