Tissue protection and endothelial cell signaling by 20-HETE analogs in intact ex vivo lung slices. Exp Cell Res 2012 Oct 01;318(16):2143-52
Date
06/13/2012Pubmed ID
22687879Pubmed Central ID
PMC3749092DOI
10.1016/j.yexcr.2012.06.005Scopus ID
2-s2.0-84864296910 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
The capacity to follow cell type-specific signaling in intact lung remains limited. 20-hydroxyeicosatetraenoic acid (20-HETE) is an endogenous fatty acid that mediates signaling for a number of key physiologic endpoints in the pulmonary vasculature, including cell survival and altered vascular tone. We used confocal microscopy to identify enhanced reactive oxygen species (ROS) production in endothelial cell (EC)s in intact lung evoked by two stable analogs of 20-HETE, 20-5,14-HEDE (20-hydroxyeicosa-5(Z),14(Z)-dienoic acid) and 20-5,14-HEDGE (N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine). These analogs generated increased ROS in cultured pulmonary artery endothelial cells as well. 20-HETE analog treatment decreased apoptosis of pulmonary tissue exposed to hypoxia-reoxygenation (HR) ex vivo. Enhanced ROS production and apoptosis were confirmed by biochemical assays. Our studies identify physiologically critical, graded ROS from ECs in live lung tissue ex vivo treated with 20-HETE analogs and protection from HR-induced apoptosis. These methodologies create exciting possibilities for studying signaling by stable 20-HETE analogs and other factors in pulmonary endothelial and other lung cell types in their native milieu.
Author List
Jacobs ER, Bodiga S, Ali I, Falck AM, Falck JR, Medhora M, Dhanasekaran AMESH terms used to index this publication - Major topics in bold
AnimalsCattle
Cell Survival
Endothelial Cells
Female
Hydroxyeicosatetraenoic Acids
Hypoxia
Lipopeptides
Lung
Microscopy, Confocal
Oxygen
Primary Cell Culture
Pulmonary Artery
Rats
Rats, Wistar
Reactive Oxygen Species
Signal Transduction
Tissue Culture Techniques