title: Vascular endothelial growth factor-D modulates oxidant-antioxidant balance of human vascular endothelial cells.
abstract: Vascular endothelial growth factor-D (VEGF-D) is an angiogenic and lymphangiogenic glycoprotein that facilitates tumour growth and distant organ metastasis. Our previous studies showed that VEGF-D stimulates the expression of proteins involved in cell-matrix interactions and promoting the migration of endothelial cells. In this study, we focused on the redox homoeostasis of endothelial cells, which is significantly altered in the process of tumour angiogenesis. Our analysis revealed up-regulated expression of proteins that form the antioxidant barrier of the cell in VEGF-D-treated human umbilical endothelial cells and increased production of reactive oxygen and nitrogen species in addition to a transient elevation in the total thiol group content. Despite a lack of changes in the total antioxidant capacity, modification of the antioxidant barrier induced by VEGF-D was sufficient to protect cells against the oxidative stress caused by hypochlorite and paraquat. These results suggest that exogenous stimulation of endothelial cells with VEGF-D induces an antioxidant response of cells that maintains the redox balance. Additionally, VEGF-D-induced changes in serine/threonine kinase mTOR shuttling between the cytosol and nucleus and its increased phosphorylation at Ser-2448, lead us to the conclusion that the observed shift in redox balance is regulated via mTOR kinase signalling.
authors.affiliation: Institute of Medical Biology, Polish Academy of Science, Lodz, Poland.
authors.forename: Izabela
authors.initials: I
authors.lastname: Papiewska-Pająk
authors.affiliation: Department of Molecular Biophysics, University of Lodz, Lodz, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Balcerczyk
authors.affiliation: Central Scientific Laboratory, Medical University of Lodz, Lodz, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Stec-Martyna
authors.affiliation: Department of Cytobiology and Proteomics, Medical University of Lodz, Lodz, Poland.
authors.forename: Wiktor
authors.initials: W
authors.lastname: Koziołkiewicz
authors.affiliation: Institute of Medical Biology, Polish Academy of Science, Lodz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Boncela
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006997:Hypochlorous Acid / Q000633:toxicity; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics*
chemical_list: D000975:Antioxidants; D016877:Oxidants; D017382:Reactive Oxygen Species; C579459:VEGFD protein, human; D042643:Vascular Endothelial Growth Factor D; D006997:Hypochlorous Acid; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: endothelial cells; mTOR; redox homoeostasis; vascular endothelial growth factor-D