Homocysteine induces congenital defects of the heart and neural tube: Effect of folic acid

作者: T. H. Rosenquist , S. A. Ratashak , J. Selhub

DOI: 10.1073/PNAS.93.26.15227

关键词:

摘要: The biological basis or mechanism whereby folate supplementation protects against heart and neural tube defects is unknown. It has been hypothesized that the amino acid homocysteine may be teratogenic agent, since serum increases in depletion; however, this hypothesis not tested. In study, avian embryos were treated directly with d,l-homocysteine l-homocysteine thiolactone, a dose response was established. Of 50 μl of (200 mM 100 thiolactone) on incubation days 0, 1, 2 harvested at 53 h (stage 14), 27% showed defects. To determine effect process septation, during 2, 3, 4; then they day 9 following completion septation. surviving embryos, 23% ventricular septal defects, 11% A high percentage also ventral closure defect. shown to raise over 150 nmol/ml, compared normal level about 10 nmol/ml. Folate kept rise ≈45 prevented effect. These results support per se causes dysmorphogenesis tube, as well wall.

参考文章(32)
J W Miller, M R Nadeau, J Smith, D Smith, J Selhub, Folate-deficiency-induced homocysteinaemia in rats: disruption of S-adenosylmethionine's co-ordinate regulation of homocysteine metabolism. Biochemical Journal. ,vol. 298, pp. 415- 419 ,(1994) , 10.1042/BJ2980415
Mary J. Seller, Vitamins, Folic Acid and the Cause and Prevention of Neural Tube Defects Ciba Foundation Symposium 181 - Neural Tube Defects. ,vol. 181, pp. 161- 179 ,(1994) , 10.1002/9780470514559.CH10
J. M. Scott, D. G. Weir, A. Molloy, J. Mcpartlin, L. Daly, P. Kirke, Folic acid metabolism and mechanisms of neural tube defects. Ciba Foundation Symposium 181 - Neural Tube Defects. ,vol. 181, pp. 180- 191 ,(2007) , 10.1002/9780470514559.CH11
John C. W. Brown, John J. Strain, Effect of dietary homocysteine on copper status in rats. Journal of Nutrition. ,vol. 120, pp. 1068- 1074 ,(1990) , 10.1093/JN/120.9.1068
Mary K. Heid, Nathan D. Bills, Steven H. Hinrichs, Andrew J. Clifford, Folate deficiency alone does not produce neural tube defects in mice. Journal of Nutrition. ,vol. 122, pp. 888- 894 ,(1992) , 10.1093/JN/122.4.888
Thomas H. Rosenquist, Judy R McCoy, Karen L. Waldo, Margaret L. Kirby, Origin and propagation of elastogenesis in the developing cardiovascular system Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology. ,vol. 221, pp. 860- 871 ,(1988) , 10.1002/AR.1092210411
M.D. Lucock, J. Wild, C.J. Schorah, M.I. Levene, R. Hartley, The methylfolate axis in neural tube defects: in vitro characterisation and clinical investigation. Biochemical Medicine and Metabolic Biology. ,vol. 52, pp. 101- 114 ,(1994) , 10.1006/BMMB.1994.1040