Premium
20‐Hydroxyeicosatetraenoic acid protects the pulmonary vasculature from apoptosis
Author(s) -
Bodiga Sreedhar,
Dunn Laurel K,
Gao Ying,
Gruenloh Stephanie K,
Buonaccorsi Noelle J,
AlSaghir Rula,
Falck John R,
Medhora Meetha M,
Jacobs Elizabeth R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1150.9
Subject(s) - apoptosis , protein kinase b , hydroxyeicosatetraenoic acid , arachidonic acid , hypoxia (environmental) , superoxide , nadph oxidase , endothelial stem cell , chemistry , pharmacology , medicine , reactive oxygen species , biochemistry , in vitro , oxygen , enzyme , organic chemistry
The arachidonic acid derivative, 20‐hydroxyeicosatetraenoic acid (20‐HETE) dilates small pulmonary arteries (~1–3 mm in diameter). We recently showed that 20‐HETE increases generation of superoxide in bovine pulmonary artery endothelial cells (BPAECs) via activation of NADPH oxidase. Superoxide is known to stimulate growth of endothelial cells and activate protein kinases including ERK, p38MAPK, and Akt. We therefore tested if 20‐HETE promoted survival of BPAEC from apoptotic cell death. 20‐HETE (10 nM – 1 microM) produced a concentration‐dependent increase in numbers of BPAECs after serum deprivation and attenuated increases in caspase 3 activity, indicating protection against apoptosis. This pro‐survival action of 20‐HETE was abolished by pharmacological inhibition of phospho‐inositide 3‐kinase and Akt. Lipopolysaccharide (LPS) induced apoptosis in BPAECs as determined by nuclear fragmentation and increased activity of caspase 3 was effectively inhibited by 20‐HETE (1 microM). Further, 20‐HETE also reduced caspase 3 activity in ex vivo cultures of small pulmonary arteries from mouse and exposed to hypoxia followed by reoxygenation. In summary, 20‐HETE protects the pulmonary vasculature from apoptosis induced my multiple insults such as serum deprivation, LPS and hypoxia/reoxygenation. Funding: NIH/NHLBI 68627 (ERJ), 49294 (ERJ), 69996 (MMM), GM 31278 (JRF).