title: 17beta-estradiol mediates protection against microvascular endothelial cell hyperpermeability.
abstract: BACKGROUND
  Previous work from our laboratory demonstrated the involvement of "intrinsic" mitochondrial apoptotic signaling in vascular hyperpermeability. The objective of this study was to determine if 17beta-estradiol, a known inhibitor of apoptosis, would attenuate microvascular endothelial cell hyperpermeability.
  
  
  METHODS
  Rat lung microvascular endothelial cell monolayers were treated with 17beta-estradiol or estrogen-receptor antagonist ICI 182780 after transfection with BAK peptide (5 microg/mL). Fluorescein isothiocyanate (FITC)-albumin was used to determine the change in permeability. Mitochondrial reactive oxygen species (ROS) formation and transmembrane potential were determined using 123 dihydrorhodamine and JC-1, respectively. Cytosolic cytochrome c levels and caspase-3 activity were determined using enzyme-linked immunosorbent assay and fluorometric assay respectively.
  
  
  RESULTS
  17beta-estradiol (10 nm) attenuated BAK-induced hyperpermeability (P < .05), ROS formation, cytochrome c release, and caspase-3 activation. The estrogen receptor antagonist ICI 182780 blocked the protective effect of 17beta-estradiol on hyperpermeability (P < .05).
  
  
  CONCLUSIONS
  17beta-estradiol attenuates BAK-induced hyperpermeability in rat lung microvascular endothelial cells by way of an estrogen-receptor mediated pathway.
authors.affiliation: Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, USA.
authors.forename: Binu
authors.initials: B
authors.lastname: Tharakan
authors.forename: Robert
authors.initials: R
authors.lastname: Corprew
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Hunter
authors.forename: J Greg
authors.initials: JG
authors.lastname: Whaley
authors.forename: W Roy
authors.initials: WR
authors.lastname: Smythe
authors.forename: Ed W
authors.initials: EW
authors.lastname: Childs
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply; D051381:Rats; D014652:Vascular Diseases / Q000517:prevention & control*
chemical_list: D002317:Cardiovascular Agents; D004958:Estradiol