17beta-estradiol mediates protection against microvascular endothelial cell hyperpermeability.
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.
Tharakan
Binu
B
Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, USA.
Corprew
Robert
R
Hunter
Felicia A
FA
Whaley
J Greg
JG
Smythe
W Roy
WR
Childs
Ed W
EW
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*
D002317:Cardiovascular Agents; D004958:Estradiol