Dietary manganese affects the concentration, composition and sulfation pattern of heparan sulfate glycosaminoglycans in Sprague-Dawley rat aorta |
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Authors: | Anastasia Z Kalea Fotini N Lamari Achilleas D Theocharis Dale A Schuschke Nikos K Karamanos Dorothy J Klimis-Zacas |
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Institution: | (1) Department of Food Science and Human Nutrition, University of Maine, Orono, ME 04469, USA;(2) Department of Pharmacy, University of Patras, 26500 Patras, Greece;(3) Laboratory of Biochemistry, Department of Chemistry, University of Patras, 26500 Patras, Greece;(4) Department of Physiology & Biophysics, School of Medicine, University of Louisville, Louisville, KY 40292, USA |
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Abstract: | We examined the effect of dietary Mn on the composition and structure of heparan sulfate (HS) glycosaminoglycans (GAGs) of
rat aorta. Animals were randomly assigned to either a Mn deficient (MnD), adequate (MnA) or supplemented (MnS) diet (Mn<1,
10–15 and 45–50 ppm, respectively). After 15 weeks, aortic tissue GAGs were isolated with papain digestion, alkaline borohydride
treatment and anion-exchange chromatography. Cellulose acetate electrophoresis and treatment of the fractions with specific
lyases revealed the presence of three GAG populations, i.e. hyaluronan (HA), heparan sulfate (HS) and galactosaminoglycans
(GalAGs). Disaccharide composition of the HS fractions was determined by HPCE following treatment with heparin lyases I, II
and III. In MnS aortas we observed increased concentration of total GalAGs and decreased concentration of HS and HA, when
compared to MnA aortas. Aortas from MnD and MnA rats appeared to have similar distribution of individual GAGs. Heparan sulfate
chains of MnS aortas contained higher (41%) concentration of non-sulfated units compared to MnA ones. Variable amounts of
trisulfated and disulfated units were found only in MnD and MnA groups but not in MnS. Our results demonstrate that HS biosynthesis
in the rat aorta undergoes marked structural modifications that depend upon dietary Mn intake. The reduced expression and
undersulfation of HSPGs with Mn supplementation might indicate a reduced ability of vascular cells to interact with biologically
active molecules such as growth factors. Alterations in cell-membrane binding ability to a variety of extracellular ligands
might affect signal-transduction pathways and arterial functional properties. |
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Keywords: | aorta disaccharides glycosaminoglycan heparan sulfate manganese |
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