Lipid rafts mediate H2O2 prosurvival effects in cultured endothelial cells. Export

@article{citeulike:912503, abstract = {Reactive oxygen species (ROS) generated during pathological events, such as inflammation and ischemia-reperfusion, activates both proapoptotic and antiapoptotic signaling programs in endothelial cells. Because cholesterol-rich, plasma membrane rafts serve as platforms for organizing and integrating signaling transduction processes, we asked whether these membrane regions play a mechanistic role in H2O2-induced responses. Bovine aortic endothelial cell cultures exposed to a 500-microM bolus of H2O2 showed progressive activation of caspase 3 and an increase in the number of TUNEL-positive cells. Pretreatment with either wortmannin or PD 098059 heightened these apoptotic responses, demonstrating that both PI3 kinase/Akt and ERK1/2 serve as signaling mediators to alleviate H2O2 cytotoxic effects. To investigate the role of lipid rafts in these signaling processes, endothelial cells were pretreated with methyl-beta-cyclodextrin (CD) or filipin to ablate raft structures. H2O2-induced phosphorylation of Akt and ERK 1/2 was attenuated, while caspase 3 and the number of TUNEL positive cells was enhanced in CD-pretreated cells exposed to H2O2. Reconstitution of raft domains restored H2O2-induced Akt and ERK1/2 phosphorylation, which was concomitant with reduction of caspase 3 activation and DNA fragmentation. Taken together, our findings suggest that plasma membrane compartments rich in cholesterol participate in signal transduction pathways activated by oxidative stress.}, address = {Cardiovascular Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine, 3420 North Broad St., MRB826, Philadelphia, Pennsylvania 19140, USA.}, author = {Yang, B. and Oo, T. N. and Rizzo, V.}, citeulike-article-id = {912503}, citeulike-linkout-0 = {http://dx.doi.org/10.1096/fj.05-5359fje}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16754746}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16754746}, comment = {Ridiculously simple experiment. Publication in FASEB J (IF 7), because of Rizzo.}, doi = {10.1096/fj.05-5359fje}, issn = {1530-6860}, journal = {FASEB J}, keywords = {akt, apoptosis, cholesterol, depletion, endothelial, erk12, rafts}, month = {July}, number = {9}, pages = {1501--1503}, posted-at = {2006-10-25 13:56:28}, priority = {4}, title = {Lipid rafts mediate H2O2 prosurvival effects in cultured endothelial cells.}, url = {http://dx.doi.org/10.1096/fj.05-5359fje}, volume = {20}, year = {2006} }

TY - JOUR ID - citeulike:912503 L3 - citeulike-article-id:912503 N2 - Reactive oxygen species (ROS) generated during pathological events, such as inflammation and ischemia-reperfusion, activates both proapoptotic and antiapoptotic signaling programs in endothelial cells. Because cholesterol-rich, plasma membrane rafts serve as platforms for organizing and integrating signaling transduction processes, we asked whether these membrane regions play a mechanistic role in H2O2-induced responses. Bovine aortic endothelial cell cultures exposed to a 500-microM bolus of H2O2 showed progressive activation of caspase 3 and an increase in the number of TUNEL-positive cells. Pretreatment with either wortmannin or PD 098059 heightened these apoptotic responses, demonstrating that both PI3 kinase/Akt and ERK1/2 serve as signaling mediators to alleviate H2O2 cytotoxic effects. To investigate the role of lipid rafts in these signaling processes, endothelial cells were pretreated with methyl-beta-cyclodextrin (CD) or filipin to ablate raft structures. H2O2-induced phosphorylation of Akt and ERK 1/2 was attenuated, while caspase 3 and the number of TUNEL positive cells was enhanced in CD-pretreated cells exposed to H2O2. Reconstitution of raft domains restored H2O2-induced Akt and ERK1/2 phosphorylation, which was concomitant with reduction of caspase 3 activation and DNA fragmentation. Taken together, our findings suggest that plasma membrane compartments rich in cholesterol participate in signal transduction pathways activated by oxidative stress. IS - 9 JF - FASEB J SN - 1530-6860 AD - Cardiovascular Research Center and Department of Anatomy and Cell Biology, Temple University School of Medicine, 3420 North Broad St., MRB826, Philadelphia, Pennsylvania 19140, USA. EP - 1503 TI - Lipid rafts mediate H2O2 prosurvival effects in cultured endothelial cells. VL - 20 SP - 1501 KW - akt KW - apoptosis KW - cholesterol KW - depletion KW - endothelial KW - erk12 KW - rafts N1 - Ridiculously simple experiment. Publication in FASEB J (IF 7), because of Rizzo. AU - Yang, B AU - Oo, TN AU - Rizzo, V PY - 2006/07// UR - http://dx.doi.org/10.1096/fj.05-5359fje ER -