Low doses of reactive oxygen species protect endothelial cells from apoptosis by increasing thioredoxin-1 expression.
The redox regulator thioredoxin-1 (Trx-1) is required for the redox potential of the cell and exerts important functions in cell growth and apoptosis. Severe oxidative stress has been implicated in the oxidation of proteins and cell death. However, the role of low doses of reactive oxygen species (ROS) is poorly understood. Here, we show that 10 and 50 microM H2O2 and short-term exposure to shear stress significantly increased Trx-1 mRNA and protein levels in endothelial cells. Since it is known that Trx-1 exerts anti-apoptotic functions, we next investigated whether low doses of ROS can inhibit basal and serum-depletion induced endothelial cell apoptosis. Indeed, treatment of endothelial cells with 10 and 50 microM H2O2 significantly reduced apoptosis induction. Reduction of Trx-1 expression using an antisense oligonucleotide approach resulted in the induction of apoptosis and abolished the inhibitory effect of low doses of H2O2. Taken together, our results demonstrate that low doses of ROS act as signaling molecules and exert anti-apoptotic functions in endothelial cells via upregulation of the redox-regulator Trx-1.
Haendeler
Judith
J
Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, Frankfurt, Germany.
Tischler
Verena
V
Hoffmann
Jörg
J
Zeiher
Andreas M
AM
Dimmeler
Stefanie
S
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033081:Shear Strength; D015398:Signal Transduction; D013879:Thioredoxins / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology
D016895:Culture Media, Serum-Free; D016376:Oligonucleotides, Antisense; D016877:Oxidants; D011506:Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D020169:Caspases