title: Superoxide dismutase 1 and glutathione peroxidase 1 are involved in the protective effect of sulodexide on vascular endothelial cells exposed to oxygen-glucose deprivation.
abstract: Sulodexide (SDX) is widely used in the treatment of both arterial and venous thrombotic disorders. In addition to its recognized antithrombotic action, SDX has endothelial protective potential, which is independent of the coagulation/fibrinolysis system. However, the detailed molecular mechanisms of the endothelioprotective action of the drug are still unresolved. The aim of the present study was to determine whether treatment with SDX at concentrations of 0.125-0.5 lipase releasing unit (LRU)/ml have on the expression and activity of antioxidant enzymes in ischemic endothelial cells and how these effects might be related to the antiapoptotic properties of SDX. In the present study, human umbilical vein endothelial cells (HUVECs) were subjected to ischemia-simulating conditions (combined oxygen and glucose deprivation, OGD) for 6h to determine the protective effects of SDX. SDX (0.25 and 0.5LRU/ml) in OGD significantly increased the cell viability and prevented mitochondrial depolarization in the HUVECs. Moreover, SDX protected the HUVECs against OGD-induced apoptosis. At concentrations of 0.25 and 0.5LRU/ml, the drug increased both superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1) mRNA/protein expression together with a significant attenuation of oxidative stress in ischemic HUVECs. Our findings also demonstrate that an increase in both SOD and GPx activity is involved in the protective effect of SDX on ischemic endothelial cells. Altogether, these results suggest that SDX has a positive effect on ischemia-induced endothelial damage because of its antioxidant and antiapoptotic properties.
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland. Electronic address: bgabryel@interia.pl.
authors.forename: Bożena
authors.initials: B
authors.lastname: Gabryel
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Jarząbek
authors.affiliation: Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Machnik
authors.affiliation: Department of Biophysics, School of Pharmacy and Laboratory Medicine, Medical University of Silesia, Jedności 8, PL 41-200 Sosnowiec, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Adamczyk
authors.affiliation: Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Belowski
authors.affiliation: Department of Pharmacology, Medical University of Silesia, Medyków 18, PL 40-752 Katowice, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Obuchowicz
authors.affiliation: Department of General and Vascular Surgery, Medical University of Silesia, Ziołowa 45/47, PL 40-635 Katowice, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Urbanek
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000172:deficiency*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013997:Time Factors; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D006025:Glycosaminoglycans; D012333:RNA, Messenger; C000606290:SOD1 protein, human; C007858:glucuronyl glucosamine glycan sulfate; D005979:Glutathione Peroxidase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005947:Glucose; D010100:Oxygen; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human
keywords: Antioxidative enzymes; Apoptosis; Endothelial cells; Ischemia; Sulodexide