17β-estradiol mediates protection against microvascular endothelial cell hyperpermeability
Presented at the 17th annual meeting of the Society of Black Academic Surgeons, April 17–20, 2008, Cleveland, OH.
Received 22 May 2008; received in revised form 10 October 2008
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 17β-estradiol, a known inhibitor of apoptosis, would attenuate microvascular endothelial cell hyperpermeability.
Methods
Rat lung microvascular endothelial cell monolayers were treated with 17β-estradiol or estrogen-receptor antagonist ICI 182780 after transfection with BAK peptide (5 μg/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
17β-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 17β-estradiol on hyperpermeability (P < .05).
Conclusions
17β-estradiol attenuates BAK-induced hyperpermeability in rat lung microvascular endothelial cells by way of an estrogen-receptor mediated pathway.
ABSTRACT