17β-estradiol mediates protection against microvascular endothelial cell hyperpermeability

Tharakan, Binu; Corprew, Robert; Hunter, Felicia A.; Whaley, J. Greg; Smythe, W. Roy; Childs, Ed W.

doi:10.1016/j.amjsurg.2008.10.003

« Previous Next »The American Journal of Surgery
Volume 197, Issue 2 , Pages 147-154, February 2009

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.

Binu Tharakan, Ph.D.
- Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, United States
- Scott and White Memorial Hospital, Temple, TX, United States
Robert Corprew, M.D.
- Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, United States
- Scott and White Memorial Hospital, Temple, TX, United States
Felicia A. Hunter, B.S.
- Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, United States
- Scott and White Memorial Hospital, Temple, TX, United States
J. Greg Whaley, M.D.
- Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, United States
- Scott and White Memorial Hospital, Temple, TX, United States
W. Roy Smythe, M.D.
- Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, United States
- Scott and White Memorial Hospital, Temple, TX, United States
Ed W. Childs, M.D.
- Department of Surgery, College of Medicine, Texas A&M University Health Science Center, Temple, TX, United States
- Scott and White Memorial Hospital, Temple, TX, United States
- Corresponding author. Tel.: +1-254-724-9087; fax: +1-254-724-7912

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).