Increased oxidative damage (DNA-protein cross-links) in copper deficient embryos: mechanism of teratogenicity

M. A. Jankowski, J. Y. Uriu-Hare, R. B. Rucker, S. N. Hawk, Carl L Keen

Research output: Contribution to journalArticle

Abstract

While it is known that copper (Cu) deficiency is teratogenic, the underlying mechanisms are poorly understood. Cu, zinc Superoxide dismutase (CuZn-SOD) is a key enzyme in oxidant defense which requires Cu for catalytic activity. We hypothesize that one mechanism underlying Cu deficiency-induced teratogenesis is oxidative damage secondary to a compromised oxidant defense system. We have observed that embryos cultured in vitro in Cu deficient serum have low SOD activity. Further, embryos cultured in Cu deficient serum supplemented with CuZn-SOD have SOD activity similar to controls, and exhibit improved development. To assess the effect of Cu deficiency in vivo, female rats were fed either a control (Con) (8 μg Cu/g) or a Cu deficient (CuD) (0.5 ng Cu/g ) diet beginning 4 weeks prior to mating. On gestation day (GD) 11, embryos were evaluated for morphological development and SOD activity. CuD and Con embryos were at a similar developmental stage on GD 11 ; however, embryos from the CuD dams were characterized by edematous hindbrain. Similar to in vitro data, embryos in the CuD group had low SOD activity. To assess the functional significance of the low SOD activity, we measured embryo DNA-protein crosslinks, an index of oxidative damage to DNA. Embryos from CuD dams had a higher percent of protein crosslinked DNA than controls. Collectively, these data support the concept that embryonic Cu deficiency can be associated with an increased risk for cellular oxidative damage which is reflected by abnormal development.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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    Jankowski, M. A., Uriu-Hare, J. Y., Rucker, R. B., Hawk, S. N., & Keen, C. L. (1996). Increased oxidative damage (DNA-protein cross-links) in copper deficient embryos: mechanism of teratogenicity. FASEB Journal, 10(3).