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Phosphatidylethanolamine modification contributes to levuglandin/isoketal induced cytotoxicity
Author(s) -
Davies Sean Stephen,
Sullivan C. Blake,
Matafonova Elena,
Roberts L. Jackson,
Amarnath Venkataraman
Publication year - 2010
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.24.1_supplement.476.3
Subject(s) - cytotoxicity , phosphatidylethanolamine , chemistry , adduct , ethanolamine , phospholipase , in vitro , biochemistry , enzyme , phospholipid , phosphatidylcholine , organic chemistry , membrane
Background Levuglandins and isoketals are γ‐ketoaldehyde isomers (IK) formed by non‐enzymatic rearrangement of prostaglandin H 2 and H 2 ‐isoprostanes, respectively. IK rapidly adduct to proteins and increases in IK protein adduct levels occur in several inflammatory conditions. IK induce cell death in cultured cells, potentially by adducting to cellular proteins. However, IK also adduct to other primary amines including phosphatidylethanolamine (PE) in vitro. Whether IK induces its biological activities by modifying PE has not been investigated. Objective Measure levels of IK‐PE in cells and determine whether IK‐ PE mediates the endothelial cell death induced by IsoK. Results 40% radiolabeled IK added to HEK cells bound to phospholipids and only 8% with proteins. An LC/MS/MS assay using S. chromofuscus phospholipase D to convert IK‐PE to IK‐ethanolamine was used to measure IK‐PE adducts in IK treated endothelial cells (EC). IK‐PE added directly to EC dose‐dependently induced cytotoxicity (LC 50 2.2 μM). Conclusion PE is a major cellular target of IK, and IK modified PE can mediate IK induced cytotoxicity.