title: Homocysteine-induced caspase-3 activation by endoplasmic reticulum stress in endothelial progenitor cells from patients with coronary heart disease and healthy donors.
abstract: Previous studies have suggested an association of hyperhomocysteinemia-induced vascular pathology with enhanced apoptotic potential of endothelial progenitor cells in patients with coronary heart disease. Our results indicate that 500 µmol/L homocysteine induced endothelial progenitor cell apoptosis and activation of caspase-3, both of which were abolished by 100 µmol/L and 200 µmol/L salubrinal, an agent that prevents endoplasmic reticulum stress-induced apoptosis. The addition of 500 µmol/L homocysteine caused a release of Ca(2+) from intracellular stores, and enhanced phosphor-eukaryotic initiation factor 2α phosphorylation at Ser51 and the expression of a glucose-regulated protein of 78 kDa and a C/EBP homologous protein independently of extracellular Ca(2+). These effects of homocysteine on endothelial progenitor cells were significantly greater in patients with coronary heart disease than in healthy donors. These findings suggest that homocysteine induces endoplasmic reticulum stress-mediated activation of caspase-3 in endothelial progenitor cells, an event that is enhanced in patients with coronary heart disease. Furthermore, enhanced endoplasmic reticulum stress-mediated activation of caspase-3 in endothelial progenitor cells might be involved in hyperhomocysteinemia-associated vascular pathology.
authors: Intensive Care Unit and Zhejiang Provincial Key Laborary of Geriatrics, Zhejiang Hospital, Hangzhou, China.
authors: Li
authors: L
authors: Li
authors: Bang-chuan
authors: BC
authors: Hu
authors: Shi-jin
authors: SJ
authors: Gong
authors: Jing
authors: J
authors: Yan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001782:Blood Donors; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002934:Cinnamates / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003327:Coronary Disease / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013890:Thiourea / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: D002934:Cinnamates; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C018551:glucose-regulated proteins; C496827:salubrinal; D006710:Homocysteine; D053148:Caspase 3; D013890:Thiourea