EUK-207 protects human intestinal microvascular endothelial cells (HIMEC) against irradiation-induced apoptosis through the Bcl2 pathway. Life Sci 2012 Oct 22;91(15-16):771-82
Date
09/04/2012Pubmed ID
22940617Pubmed Central ID
PMC3520131DOI
10.1016/j.lfs.2012.08.018Scopus ID
2-s2.0-84867331082 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
AIM: To elucidate the signaling mechanisms involved in the protective effect of EUK-207 against irradiation-induced cellular damage and apoptosis in human intestinal microvasculature endothelial cells (HIMEC).
METHODS: HIMECs were irradiated and treated with EUK-207. Using hydroethidine and DCF-DA fluorescent probe the intracellular superoxide and reactive oxygen species (ROS) were determined. By real-time PCR and western blotting caspase-3, Bcl2 and Bax genes and proteins were analyzed. Proliferation was determined by [(3)H]-thymidine uptake. Immunofluorescence staining was used for translocation of p65 NFκB subunit.
KEY FINDING: Irradiation increased ROS production, apoptosis, Bax, Caspase3 and NFkB activity in HIMEC and inhibited cell survival/growth/proliferation. EUK-207 restored the endothelial functions, markedly inhibited the ROS, up-regulated the Bcl2 and down-regulated Bax and prevented NFκB caspase 3 activity in HIMEC.
SIGNIFICANCE: HIMEC provide a novel model to define the effect of irradiation induced endothelial dysfunction. Our findings suggest that EUK-207 effectively inhibits the damaging effect of irradiation.
Author List
Otterson MF, Nie L, Schmidt JL, Link BJ, Jovanovic N, Lyros O, Rafiee PAuthor
Mary F. Otterson MS, MD Emeritus Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ApoptosisCaspase 3
Cell Line
Cell Movement
Cytoprotection
Endothelial Cells
Free Radical Scavengers
Humans
Intestines
L-Lactate Dehydrogenase
Malondialdehyde
NF-kappa B
Organometallic Compounds
Proto-Oncogene Proteins c-bcl-2
RNA, Messenger
Reactive Oxygen Species
Signal Transduction
Superoxide Dismutase
bcl-2-Associated X Protein
