title: Physiologic concentrations of magnesium and placental apoptosis: prevention by antioxidants.
abstract: OBJECTIVE
  To identify the role of physiologic magnesium concentrations on the induction of placental apoptosis in vitro and test the anti-apoptotic action of antioxidants.
  
  
  METHODS
  Placental tissue was obtained from normal pregnancies after cesarean delivery. Placental explants were incubated with increasing concentrations of extracellular magnesium (range 0-2.0 mM). Placental apoptosis was evaluated by tissue morphology, DNA fragmentation, cytokeratin-18 neoepitope formation, and cleavage of plasminogen activator inhibitor type 2.
  
  
  RESULTS
  Physiologic concentrations of extracellular magnesium stimulated placental apoptosis. Magnesium stimulated apoptosis within the physiologic range (0.8-1.2 mM) (n = 6, P <.001) and was associated with cleavage of plasminogen activator inhibitor type 2 and cytokeratin-18 neoepitope formation. These data implicate caspase activation in the transduction of the magnesium-induced apoptotic signal. Therapeutic concentrations of vitamin C, vitamin E, and acetylcysteine (all at 25 microg/mL) inhibited DNA fragmentation and attenuated cleavage of plasminogen activator inhibitor type 2 and cytokeratin-18 neoepitope formation.
  
  
  CONCLUSIONS
  Magnesium-induced placental apoptosis is a potent mechanism of placental degeneration in vitro and may represent an important regulator of placental tissue dynamics in vivo. The ability of antioxidants to prevent magnesium-induced placental apoptosis implicates oxidation-reduction-dependent signaling events in this process. Furthermore, these findings provide a basis for further studies of antioxidants in mitigating the adverse effects of preeclampsia.
authors.affiliation: Department of Medicine, Monash University, Box Hill Hospital, Box Hill, Victoria, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Black
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Sachchithananthan
authors.forename: R L
authors.initials: RL
authors.lastname: Medcalf
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001205:Ascorbic Acid / Q000494:pharmacology; D046508:Culture Techniques; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology / Q000502:physiology*; D015636:Magnesium Chloride / Q000494:pharmacology; D008278:Magnesium Sulfate / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism / Q000502:physiology*; D017396:Plasminogen Activator Inhibitor 2 / Q000378:metabolism; D011247:Pregnancy; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017396:Plasminogen Activator Inhibitor 2; D015636:Magnesium Chloride; D014810:Vitamin E; D007633:Keratins; D008278:Magnesium Sulfate; D008274:Magnesium; D001205:Ascorbic Acid; D000111:Acetylcysteine