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Comparison of vitamin C deficiency with food restriction on collagen cross-link ratios in bone, urine and skin of weanling guinea-pigs

Published online by Cambridge University Press:  09 March 2007

Harumi Tsuchiya
Affiliation:
MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
C. J. Bates*
Affiliation:
MRC Human Nutrition Research, Elsie Widdowson Laboratory, Fulbourn Road, Cambridge CB1 9NL, UK
*
Corresponding author: Dr Chris Bates, fax +44 1223 437515, email Chris.Bates@mrc-hnr.cam.ac.uk
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Abstract

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Mild-to-moderate vitamin C depletion in weanling guinea-pigs affects pyridinoline:deoxypyridinoline (collagen cross-link) ratios in femur shaft and urine, attributed to impairment of hydroxylation of collagen lysine. We investigated: (1) whether the picture at two time points is compatible with progressive accumulation of abnormal collagen; (2) whether any changes are seen in skin, where little deoxypyridinoline occurs; (3) whether total food restriction has similar effects. Male weanling Dunkin–Hartley guinea-pigs were fed diets containing either 0·5 (vitamin C-restricted) or 160·0–320·0 (vitamin C-adequate) mg vitamin /. Two groups receiving the vitamin C-adequate diet received it ad libitum. Two other groups received the vitamin C-adequate diet in a restricted amount, limited to that which permitted nearly the same growth rate as in the vitamin C-restricted groups. Animals were fed for 4 or 8 weeks; urine was collected, and vitamin C and collagen indices were measured. In the femur shaft, the hydroxyproline content per unit weight was unaffected by vitamin C restriction or by total food restriction. Deoxypyridinoline was increased and the pyridinoline:deoxypyridinoline ratio was decreased in vitamin C-restricted groups, but not in food-restricted groups. Changes in the value of the ratio were greater after 8 than after 4 weeks. Urine indices mirrored bone indices. In skin, the main effect of vitamin C restriction was to reduce hydroxyproline. Here, the cross-link ratios changed less markedly than in bone, and there was less deoxypyridinoline. We conclude that the picture at two time points is compatible with a progressive accumulation of pyridinoline-enriched collagen in vitamin C-deprived animals, that the picture in skin differs from that of bone and urine, and that cross-link changes are not produced by total food restriction.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2003

References

Acil, Y, Brinkmann, J, Notbohm, H, Muller, PK & Batge, B (1996) Changes with age in the urinary excretion of hyroxyly-sylpyridinoline (HP) and lysylpyridinoline (LP). Scandivanian Journal of Clinical and Laboratory Medicine 56, 275283.CrossRefGoogle ScholarPubMed
Bailey, AJ, Paul, RG & Knott, L (1998) Mechanisms of maturation and ageing of collagen. Mechanisms of Ageing and Development 106, 156.CrossRefGoogle ScholarPubMed
Barnes, MJ, Constable, BJ, Morton, LF & Kodicek, E (1970) Studies in vivo on the biosynthesis of collagen and elastin in ascorbic acid-deficient guinea-pigs: Evidence for the formation and degration of a partiailly hydroxylated collagen. Biochemical Journal 113, 575585.CrossRefGoogle Scholar
Barnes, MJ & Kodicek, E (1972) Biological hydroxylations and ascorbic acid with special regard to collagen metabolism. Vitamins and Hormones 30, 143.CrossRefGoogle ScholarPubMed
Branca, F, Robins, SP, Ferro-Luzzi, A & Golden, MHN (1992) Bone turnover in malnourished children. Lancet 340, 14931496.CrossRefGoogle ScholarPubMed
Chojkier, M, Spanheimer, R & Peterkofsky, B (1983) Specially decreased colagen biosynthesis in scurvy dissociated from an effect on proline hydroxylation and correlated with body weight loss. In vitro studies in guinea pig calvarial bones. Journal of Clinical Investigation 72, 826835.CrossRefGoogle Scholar
Clarke, HE, Coates, ME, Eva, KJ, Ford, DJ, Milner, CK, O'Donaghue, PN, Scott, PP & Ward, RJ (1977) Dietary standards for laboratory animals: Report of the Laboratory Animals Centre Diets Advisory Committee. Laboratory Animals 11, 128.CrossRefGoogle ScholarPubMed
Dembure, PP, Janko, AR, Priest, RE & Elsas, LJ (1987) Ascorbate regulation of collagen biosynthesis in Ehlers–Danlos syndrome. Metabolism 36, 687691.CrossRefGoogle ScholarPubMed
Elsas, LJ, Miller, RL & Pinnell, SR (1978) Inherited human collagen lysyl hydroxylase deficiency: ascorbic acid response. Journal of Pediatrics 92, 378384.CrossRefGoogle ScholarPubMed
Greenfield, H, Briggs, GM, Watson, RHJ & Yudkin, J (1969) An improved diet for carbohydrate preference studies with rats: some criticisms of experimental diets. Proceedings of the Nutrition Society 28, 43A.Google ScholarPubMed
Ho, K-C & Pang, CP (1989) Automated analysis of urinary hydroxyproline. Clinica Chimica Acta 185, 191196.CrossRefGoogle ScholarPubMed
Kim, M, Otsuka, M, Shimamura, E & Arakawa, N (1998) The effect of L-ascorbic acid on age-related changes of pyridinoline in cartilage collagen of guinea pigs. Journal of Nutritional Science and Vitaminology 44, 217224.CrossRefGoogle ScholarPubMed
Kivirikko, KI & Myllyla, R (1982) Posttranslational enzymes in the biosynthesis of collagen: intracellular enzymes. Methods in Enzymology 82, 245304.CrossRefGoogle ScholarPubMed
Myllyla, R, Majamaa, J, Gunzler, V, Hanauske-Abel, HM & Kivirikko, KI (1984) Ascorbate is consumed stoichiometrically in the uncoupled reactions catalysed by prolyl-4-hydroxylase and lysyl hydroxylase. Journal of Biological Chemistry 259, 54035405.CrossRefGoogle Scholar
Pasquali, M, Dembure, PP, Still, MJ & Elsas, LJ (1994) Urinary pyridinium cross-links: a non-invasive test for Ehlers–Danlos syndrome type VI. New England Journal of Medicine 331, 132133.CrossRefGoogle Scholar
Pasquali, M, Still, MJ, Vales, T, Rosen, RI, Evinger, JD, Dembure, PP, Longo, N & Elsas, LJ (1997) Abnormal formation of collagen cross-links in skin fibroblasts cultured from patients with Ehlers–Danlos syndrome type VI. Proceedings of the Association of American Physicians 109, 3341.Google ScholarPubMed
Peterkofsky, B (1991) Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. American Journal of Clinical Nutrition 54, 1135S1140S.CrossRefGoogle ScholarPubMed
Peterkofsky, B, Palka, J, Wilson, S, Takeda, K & Shah, V (1991) Elevated activity of low molecular weight insulin-like growth factor-binding proteins in sera of vitamin C-deficient and fasted guinea pigs. Endocrinology 128, 17691779.CrossRefGoogle ScholarPubMed
Pinnell, SR, Krane, SM, Kenzora, JE & Glimcher, MJ (1972) A heritable disorder of connective tissue. Hydroxylysine-deficient collagen disease. New England Journal of Medicine 286, 10131020.CrossRefGoogle ScholarPubMed
Robins, SP (1982) An enzyme-linked immunoassay for the collagen cross-link pyridinoline. Biochemical Journal 207, 617620.CrossRefGoogle ScholarPubMed
Robins, SP (1988) Functional properties of collagen and elastin. Ballière's Clinical Rheumatology 2, 135.CrossRefGoogle ScholarPubMed
Robins, SP (1994) Biochemical markers for assessing skeletal growth. European Journal of Clinical Nutrition 48, Suppl. 1, S199S209.Google ScholarPubMed
Robins, SP, Woitge, H, Hesley, R, Ju, J, Seyedin, S & Seibel, MJ (1994) Ascorbate can act as an inducer of the collagen pathway because most steps are tightly controlled. Annals of the New York Academy of Sciences 498, 172185.Google Scholar
Schwarz, RI, Kleinman, P & Owens, N (1987) Ascorbate can act as an inducer of the collagen pathway because most steps are tightly coupled. Annals of the New York Academy of Sciences 498, 172185.CrossRefGoogle ScholarPubMed
Spanheimer, RG & Peterkofsky, B (1985) A specific decrease in collagen synthesis in acutely fasted, vitamin C-supplemented, guinea pigs. Journal of Biological Chemistry 260, 39553962.CrossRefGoogle ScholarPubMed
Tsuchiya, H & Bates, CJ (1997) Vitamin C and copper interactions in guinea-pigs and a study of collagen cross-links. British Journal of Nutrition 77, 315325.CrossRefGoogle Scholar
Tsuchiya, H & Bates, CJ (1998) Changes in collagen cross-link ratios in bone and urine of guinea pigs fed graded dietary vitamin C: A functional index of vitamin C status. Journal of Nutritional Biochemistry 9, 402407.CrossRefGoogle Scholar
Vuilleumier, JP & Keck, E (1989) Fluorometric assay of vitamin C in biological materials, using a centrifugal analyser with fluorescence attachment. Journal of Micronutrient Analysis 5, 2534.Google Scholar