title: The challenging environment on board the International Space Station affects endothelial cell function by triggering oxidative stress through thioredoxin interacting protein overexpression: the ESA-SPHINX experiment.
abstract: Exposure to microgravity generates alterations that are similar to those involved in age-related diseases, such as cardiovascular deconditioning, bone loss, muscle atrophy, and immune response impairment. Endothelial dysfunction is the common denominator. To shed light on the underlying mechanism, we participated in the Progress 40P mission with Spaceflight of Human Umbilical Vein Endothelial Cells (HUVECs): an Integrated Experiment (SPHINX), which consisted of 12 in-flight and 12 ground-based control modules and lasted 10 d. Postflight microarray analysis revealed 1023 significantly modulated genes, the majority of which are involved in cell adhesion, oxidative phosphorylation, stress responses, cell cycle, and apoptosis. Thioredoxin-interacting protein was the most up-regulated (33-fold), heat-shock proteins 70 and 90 the most down-regulated (5.6-fold). Ion channels (TPCN1, KCNG2, KCNJ14, KCNG1, KCNT1, TRPM1, CLCN4, CLCA2), mitochondrial oxidative phosphorylation, and focal adhesion were widely affected. Cytokine detection in the culture media indicated significant increased secretion of interleukin-1α and interleukin-1β. Nitric oxide was found not modulated. Our data suggest that in cultured HUVECs, microgravity affects the same molecular machinery responsible for sensing alterations of flow and generates a prooxidative environment that activates inflammatory responses, alters endothelial behavior, and promotes senescence.
authors.affiliation: 1CNR-ISTM, Institute of Molecular Science and Technologies, Via Golgi 19, 20133 Milan, Italy. silvia.bradamante@istm.cnr.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Versari
authors.forename: Giulia
authors.initials: G
authors.lastname: Longinotti
authors.forename: Livia
authors.initials: L
authors.lastname: Barenghi
authors.forename: Jeanette Anne Marie
authors.initials: JA
authors.lastname: Maier
authors.forename: Silvia
authors.initials: S
authors.lastname: Bradamante
mesh_terms: D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002448:Cell Adhesion; D002453:Cell Cycle; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005118:Extraterrestrial Environment; D020869:Gene Expression Profiling; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D018472:Hypogravity; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D018531:Spacecraft; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D006360:Heat-Shock Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C486715:TXNIP protein, human
keywords: focal adhesion; human umbilical vein endothelial cells; microarray; microgravity; spaceflight