Ferulic Acid Mitigates Radiation Injury in Human Umbilical Vein Endothelial Cells In Vitro via the Thrombomodulin Pathway. 2018

Shuai Shao, and Yue Gao, and Jianxiang Liu, and Mei Tian, and Qiao Gou, and Xu Su
a   National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China.

Cell death and tissue injury occur as a result of radiation accidents and radiotherapy. The role of endothelial cell damage in mediating radiation-induced acute tissue injury has been extensively studied. We previously demonstrated that ferulic acid (FA) mitigates radiation-induced hematopoietic injury in mice and lessens radiation-induced oxidative damage in human umbilical vein endothelial cells (HUVECs). The purpose of the current study was to determine whether FA can protect HUVECs from radiation toxicity in a cell model via the thrombomodulin (Thbd) pathway, an anti-radiation pathway with anticoagulant, anti-inflammatory and antioxidant properties. HUVEC culture media was supplemented with FA 12 h before 4 Gy 60Co gamma irradiation. At 30 min postirradiation, the FA media was refreshed, then renewed once daily. HUVEC injury was assessed at day 5 postirradiation through cell proliferation analysis. Ferulic acid significantly ameliorated HUVEC radiation injury, as evidenced by increases in cell viability and angiogenesis and decreases in G2/M cell cycle arrest and levels of high mobility group box 1 protein (HMGB1), interleukin (IL)-6 and IL-8. These findings can be attributed to the effect of FA on the Thbd promoter, resulting in increased expression of Thbd and activated protein C with associated radioprotection. These observations indicate that FA intervention significantly ameliorates HUVEC radiation injury via the Thbd pathway. Therefore, FA could be further developed as a potential agent to mitigate radiation-induced damage.

UI MeSH Term Description Entries
D011832 Radiation Injuries Harmful effects of non-experimental exposure to ionizing or non-ionizing radiation in VERTEBRATES. Radiation Sickness,Radiation Syndrome,Injuries, Radiation,Injury, Radiation,Radiation Injury,Radiation Sicknesses,Radiation Syndromes,Sickness, Radiation,Sicknesses, Radiation,Syndrome, Radiation,Syndromes, Radiation
D003373 Coumaric Acids Hydroxycinnamic acid and its derivatives. Act as activators of the indoleacetic acid oxidizing system, thereby producing a decrease in the endogenous level of bound indoleacetic acid in plants. Coumaric Acid,Hydroxycinnamic Acid,Hydroxycinnamic Acids,Acid, Coumaric,Acid, Hydroxycinnamic,Acids, Coumaric,Acids, Hydroxycinnamic
D005720 Gamma Rays Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source. Gamma Wave,Gamma Radiation,Nuclear X-Rays,Radiation, Gamma,X-Rays, Nuclear,Gamma Radiations,Gamma Ray,Gamma Waves,Nuclear X Rays,Nuclear X-Ray,Ray, Gamma,Wave, Gamma,Waves, Gamma,X Rays, Nuclear,X-Ray, Nuclear
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000975 Antioxidants Naturally occurring or synthetic substances that inhibit or retard oxidation reactions. They counteract the damaging effects of oxidation in animal tissues. Anti-Oxidant,Antioxidant,Antioxidant Activity,Endogenous Antioxidant,Endogenous Antioxidants,Anti-Oxidant Effect,Anti-Oxidant Effects,Anti-Oxidants,Antioxidant Effect,Antioxidant Effects,Activity, Antioxidant,Anti Oxidant,Anti Oxidant Effect,Anti Oxidant Effects,Anti Oxidants,Antioxidant, Endogenous,Antioxidants, Endogenous
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D061307 Human Umbilical Vein Endothelial Cells Endothelial cells that line venous vessels of the UMBILICAL CORD. Human Umbilical Vein Endothelial Cell,Endothelial Cells, Human Umbilical Vein,HUVEC Cells,Cell, HUVEC,Cells, HUVEC,HUVEC Cell
D018180 Thrombomodulin A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation.

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