Short-term weightlessness produced by parabolic flight maneuvers altered gene expression patterns in human endothelial cells.
This study focused on the effects of short-term microgravity (22 s) on the gene expression and morphology of endothelial cells (ECs) and evaluated gravisensitive signaling elements. ECs were investigated during four German Space Agency (Deutsches Zentrum für Luft- und Raumfahrt) parabolic flight campaigns. Hoechst 33342 and acridine orange/ethidium bromide staining showed no signs of cell death in ECs after 31 parabolas (P31). Gene array analysis revealed 320 significantly regulated genes after the first parabola (P1) and P31. COL4A5, COL8A1, ITGA6, ITGA10, and ITGB3 mRNAs were down-regulated after P1. EDN1 and TNFRSF12A mRNAs were up-regulated. ADAM19, CARD8, CD40, GSN, PRKCA (all down-regulated after P1), and PRKAA1 (AMPKα1) mRNAs (up-regulated) provide a very early protective mechanism of cell survival induced by 22 s microgravity. The ABL2 gene was significantly up-regulated after P1 and P31, TUBB was slightly induced, but ACTA2 and VIM mRNAs were not changed. β-Tubulin immunofluorescence revealed a cytoplasmic rearrangement. Vibration had no effect. Hypergravity reduced CARD8, NOS3, VASH1, SERPINH1 (all P1), CAV2, ADAM19, TNFRSF12A, CD40, and ITGA6 (P31) mRNAs. These data suggest that microgravity alters the gene expression patterns and the cytoskeleton of ECs very early. Several gravisensitive signaling elements, such as AMPKα1 and integrins, are involved in the reaction of ECs to altered gravity.
Department of Nuclear Medicine, University of Regensburg, Regensburg, Germany.
Jirka
J
Grosse
Markus
M
Wehland
Jessica
J
Pietsch
Xiao
X
Ma
Claudia
C
Ulbrich
Herbert
H
Schulz
Katrin
K
Saar
Norbert
N
Hübner
Jens
J
Hauslage
Ruth
R
Hemmersbach
Markus
M
Braun
Jack
J
van Loon
Nicole
N
Vagt
Manfred
M
Infanger
Christoph
C
Eilles
Marcel
M
Egli
Peter
P
Richter
Theo
T
Baltz
Ralf
R
Einspanier
Soroush
S
Sharbati
Daniela
D
Grimm
D001483:Base Sequence; D021941:Caveolae / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013026:Space Flight; D013997:Time Factors; D014893:Weightlessness / Q000009:adverse effects*
D017931:DNA Primers; D012333:RNA, Messenger