title: Cytoprotective effect of dieckol on human endothelial progenitor cells (hEPCs) from oxidative stress-induced apoptosis.
abstract: Although endothelial progenitor cells (EPCs) have been used to promote revascularization after peripheral or myocardial ischemia, excess amounts of reactive oxygen species (ROS) are often involved in senescence and apoptosis of EPCs, thereby causing defective neovascularization and reduced or failed recovery. Here, we examined the cytoprotective effect of Ecklonia cava-derived antioxidant dieckol (DK) on oxidative stress-induced apoptosis in EPCs to improve EPC bioactivity for vessel repair. Although H2O2 (10 (- 3) M) increased the intracellular ROS level in EPCs, DK (10ug/ml) pretreatment suppressed the H2O2-induced ROS increase and drastically reduced the ratios of apoptotic cells. H2O2-induced ROS increased the phosphorylation of p38 MAPK and JNK; this was inhibited by DK pretreatment. H2O2 treatment increased the phosphorylation of NF-κB, which was blocked by pretreatment with SB 203580, a p38 MAPK inhibitor, or SP 600125, a JNK inhibitor. H2O2 decreased the cellular levels of Bcl-2 and c-IAPs, cellular inhibitors of apoptosis proteins, but increased caspase-3 activation. However, all these effects were inhibited by pretreatment with DK. Injection of DK-mixed EPCs (DK + EPCs) into myocardial ischemic sites in vivo induced cellular proliferation and survival of cells at the ischemic sites and, thereby, enhanced the secretion of angiogenic cytokines at the ischemic sites. These results show that DK + EPC exhibit markedly enhanced anti-apoptotic and antioxidative capabilities, unlike that shown by EPCs alone; thus, they contribute to improved repair of ischemic myocardial injury through cell survival and angiogenic cytokine production.
authors.affiliation: Department of Physiology, Laboratory for Vascular Medicine & Stem Cell Biology, Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: J Y
authors.initials: JY
authors.lastname: Kim
authors.forename: S Y
authors.initials: SY
authors.lastname: Yoo
authors.forename: S M
authors.initials: SM
authors.lastname: Kwon
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001572:Benzofurans / Q000494:pharmacology*; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D001572:Benzofurans; D017382:Reactive Oxygen Species; C503840:dieckol; D006861:Hydrogen Peroxide