Novel aspects of vitamin A metabolism in the dog: distribution of lipoprotein retinyl esters in vitamin A-deprived and cholesterol-fed animals

Wilson, Dana E.; Hejazi, J.; Elstad, Nancy L.; Chan, Ing-Fong; Gleeson, Jeremy M.; Iverius, Per-Henrik

doi:10.1016/0005-2760(87)90047-6

Cited by 32 publications

(23 citation statements)

References 16 publications

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“…In this study we are the first to show that THP might be involved in vitamin A metabolism as well. It has previously been speculated that the excretion of vitamin A in the urine of canines is regulated, instead of being a simple process of glomerular filtration because of the differences in the retinyl ester pattern between plasma (primarily retinyl stearate) and urine (nearly exclusively retinyl palmitate), and because of the size of the lipoproteins, which are carriers of retinyl esters in the blood plasma [19,24,30]. Since the excretion of vitamin A in the urine is not as dependent on the concentration of vitamin A in the plasma as on the amount of vitamin A in the diet [22], the knowledge of the protein carrier will greatly help to elucidate those signals and mechanisms on the cellular and molecular levels that are responsible for the regulated excretion of vitamin A in the urine of canines.…”

Section: Discussionmentioning

confidence: 99%

Vitamin A excreted in the urine of canines is associated with a Tamm-Horsfall like protein

Schweigert¹,

Raila²,

Haebel

2002

Vet. Res.

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-Under physiological conditions canines transport vitamin A in blood plasma primarily as retinyl esters bound to lipoproteins and excrete substantial amounts of vitamin A as retinol and retinyl esters with urine. In the aqueous environment of urine, the hydrophobic vitamin A has to be associated with a protein. This vitamin A-protein complex was purified to homogeneity, prepared by preparative ultracentrifugation (density 1.21 g/mL), native polyacrylamide gel electrophoresis (PAGE) and size exclusion chromatography. The vitamin A-protein complex has a high molecular mass of > 5 000 kDa under native conditions. SDS PAGE under reduced conditions revealed a single band with a molecular mass of about 100 kDa for the protein moiety. Peptides obtained after limited proteolysis with trypsin from the 100 kDa protein were characterised by MALDI-TOF mass spectrometry and showed amino acid sequence homology to the human Tamm-Horsfall Protein (THP). This was further confirmed by a positive immunoreaction of the isolated protein with crossreacting human THP antibodies. The localisation of THP in dog kidneys was determined by using immunohistology. The reaction was strong along the entire thick ascending limb of the Henle loop and distal convoluted tubule. Our data point to the possibility that THP functions as a novel carrier for vitamin A in the urine of canines. l'environnement aqueux de l'urine, la vitamine A hydrophobe doit être associée à une protéine. Ce complexe protéine-vitamine A a été purifié et homogénéisé, préparé par ultracentrifugation (1,21 g/mL de densité), électrophorèse sur gel de polyacrylamide natif (PAGE) et chromatographie d'exclusion de taille. Le complexe protéine-vitamine A a une masse moléculaire élevée supérieure à 5 000 kDa dans les conditions natives. Le SDS PAGE effectué dans des conditions réduites a révélé une bande unique avec une masse moléculaire d'environ 100 kDa pour la partie protéique. Les peptides obtenus à partir de la protéine de 100 kDa, après protéolyse limitée avec de la trypsine, ont été caractérisés par spectrométrie de masse MALDI-TOF et ont montré une homologie de séquence en acides aminés avec la protéine Tamm-Horsfall (PTH) humaine. Ceci a été confirmé par une immuno-réaction positive entre la protéine isolée et les anticorps présentant une réaction croisée avec la PTH humaine. La localisation de la PTH dans le rein de chien a été déterminée par immunohistologie. La réaction a été forte tout le long de la section ascendante épaisse de l'anse de Henle, et du tubule contourné distal. Nos résultats suggèrent que la PTH fonctionne comme un nouveau transporteur pour la vitamine A dans l'urine des canidés.vitamine A / canidés / rein / urine / protéine Tamm-Horsfall

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Section: Discussionmentioning

confidence: 99%

Vitamin A excreted in the urine of canines is associated with a Tamm-Horsfall like protein

Schweigert¹,

Raila²,

Haebel

2002

Vet. Res.

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“…Surprisingly, there was no difference in the excursions of LDL between wild-type and the LDLR(Ϫ/Ϫ) mice (Fig. 2, LDL panel), indicating that [ 3 H]retinyl ester in the LDL fraction was not derived from resecreted hepatogenous VLDL as was observed in dogs (30) and that transfer of [ 3 H]retinyl ester in chylomicron to LDL is negligible in mice. Comparable amounts of fat and retinol should have been absorbed because the excursions of the radioactivities in the d Ͼ1.063 g/ml fraction were similar (Fig.…”

Section: Figurementioning

confidence: 91%

Role of the Low Density Lipoprotein (LDL) Receptor Pathway in the Metabolism of Chylomicron Remnants

Ishibashi

Perrey

Chen

et al. 1996

Journal of Biological Chemistry

108

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Two receptor pathways are thought to mediate the hepatic clearance of chylomicron remnants, (i) the low density lipoprotein receptor (LDLR) pathway and (ii) non-LDLR pathway. The current study was undertaken to quantitatively assess the contribution of each receptor pathway to hepatic catabolism of chylomicron remnants, by using mice that are deficient in apolipoprotein E (apoE) (apoE(؊/؊)), the LDLR (LDLR(؊/؊)), and both (apoE(؊/؊);LDLR(؊/؊)). Vitamin A fat tolerance tests showed that the area under the curves of the plasma excursions of retinyl ester in the LDLR(؊/؊), apoE(؊/؊), and apoE(؊/؊);LDLR(؊/؊) mice were 4, 12, and 12 times larger than those in wild-type mice. The retinyl ester accumulated in the plasma of the LDLR(؊/؊) mice was distributed in larger subfractions of triglyceride-rich lipoproteins, chylomicrons through very low density lipoprotein-C. These results indicate that the LDLR constitutes the major pathway for the clearance of retinyl ester. In support of this, agarose gel electrophoresis revealed that an oral fat load resulted in retention of chylomicrons in the LDLR(؊/؊) mice, which was not seen in wild-type mice. The observation that the apoE(؊/؊) mice showed larger retinyl ester excursion than LDLR(؊/؊) mice indicates that an apoE-dependent non-LDLR pathway is involved in the rest of the clearance of the retinyl ester. Together, we conclude that the LDLR pathway plays a significant role in the chylomicron remnant metabolism in mice fed a normal chow.In mammals including humans, dietary fat is absorbed by the small intestine, packaged in the chylomicrons, and transported through the lymphatic system to the systemic circulation. Lipoprotein lipase hydrolyzes the core triglycerides of chylomicrons, converting them to chylomicron remnants. The remnants are rapidly cleared by the liver. This step of rapid hepatic clearance has been thought to involve several different processes (for review see Refs. 1-3). The initial process is sequestration of chylomicron remnants into the space of Disse, conceivably through the interaction of apoE on the lipoprotein particles with heparan sulfate proteoglycan (HSPG) 1 on the cell surface (4, 5). Subsequent steps might involve further lipolysis of the remnants by hepatic lipase (6, 7) and acquisition of apoE secreted from the liver (8, 9). The final step appears to involve the cellular uptake of the lipoproteins, mainly by receptor-mediated endocytosis. ApoE is essential for the hepatic removal of chylomicron remnants, as evidently demonstrated by the fact that apoEdeficient humans (10, 11) and mice (12, 13) develop severe plasma retention of chylomicron remnants. As to the role of the low density lipoprotein receptor (LDLR) in the rapid plasma clearance of chylomicron remnants, conflicting results have been reported.Several evidences have suggested that the role of LDLR in the hepatic clearance of chylomicron remnants is marginal, if present. First, in LDLR-deficient humans (14) and rabbits (15), accumulation of chylomicron remnants in the plasma is barely de...

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“…The higher plasma concentrations are due to a high percentage of retinyl esters, which are bound to lipoproteins of very low, low and high density (VLDL, LDL, HDL) in the blood plasma of canines [23,35]. This might indicate that the majority of these retinyl esters in canine plasma are of hepatic and not intestinal origin [15].…”

Section: Vitamin a Transport In Blood Plasmamentioning

confidence: 99%

“…Elevated retinyl ester levels in plasma are observed under conditions of acute or chronic vitamin A intoxication [14,30] or as a postprandial consequence of vitamin A absorption [6]. Carnivores, however, differ profoundly from this observation because most canines and mustelids transport vitamin A in blood plasma not only as retinol but predominantly as retinyl esters, bound to lipoproteins [23,25,35]. The high levels of lipoprotein bound retinyl esters in carnivores are not homeostatically regulated as is retinol, but depend greatly on actual vitamin A intake in food [24,26].…”

Section: Introductionmentioning

confidence: 99%

The distribution of vitamin A and retinol-binding protein in the blood plasma, urine, liver and kidneys of carnivores

Raila¹,

Buchholz

Aupperle

et al. 2000

Vet. Res.

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-The contents of retinol and retinyl esters as well as retinol-binding protein (RBP) in the plasma, urine, liver and kidneys of dogs, raccoon dogs and silver foxes were investigated. In the plasma and urine of all three species, vitamin A was present as retinol and retinyl esters. Vitamin A levels (1 376 ± 669 µg·g -1 ) were significantly higher in the livers of dogs than in the kidneys (200 ± 217 µg·g -1 , P < 0.001). However, vitamin A levels in the kidneys of raccoon dogs (291 ± 146 µg·g -1 ) and silver foxes (474 ± 200 µg·g -1 ) were significantly higher than in the liver (67 ± 58 µg·g -1 and 4.3 ± 2.4 µg·g -1 , respectively, both P < 0.001). RBP was immunologically detected in the blood plasma of all species, but never in the urine. In the liver, immunoreactive RBP was found in hepatocytes. In the kidneys of all species, RBP was observed in the cells of the proximal convoluted tubules. The levels of vitamin A in the livers of raccoon dogs and silver foxes were extremely low, which would be interpreted as a sign of great deficiency in humans. This observation might indicate that the liver status cannot be used as an indicator of vitamin A deficiency in canines. The high levels of vitamin A in the kidneys in all three species may indicate a specific function of the kidney in the vitamin A metabolism of canines.

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Novel aspects of vitamin A metabolism in the dog: distribution of lipoprotein retinyl esters in vitamin A-deprived and cholesterol-fed animals

Cited by 32 publications

References 16 publications

Vitamin A excreted in the urine of canines is associated with a Tamm-Horsfall like protein

Vitamin A excreted in the urine of canines is associated with a Tamm-Horsfall like protein

Role of the Low Density Lipoprotein (LDL) Receptor Pathway in the Metabolism of Chylomicron Remnants

The distribution of vitamin A and retinol-binding protein in the blood plasma, urine, liver and kidneys of carnivores

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