Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis

Scientific Reports
Yoshinori SekoKimie Murayama

Abstract

Oxidative stress plays a critical role in ischemia/reperfusion-injury, atherosclerosis, and aging. It causes cell damage that leads to apoptosis via uncertain mechanisms. Because conditioned medium from cardiac myocytes subjected to hypoxia/reoxygenation induces extensive apoptosis of cardiac myocytes under normoxia, we hypothesized that a humoral factor released from the hypoxic/reoxygenated cardiac myocytes mediates apoptosis. We identified an apoptosis-inducing humoral factor in the hypoxia/reoxygenation-conditioned medium. Here, we found that eIF5A undergoes tyrosine sulfation in the trans-Golgi and is rapidly secreted from cardiac myocytes in response to hypoxia/reoxygenation; then, eIF5A induces apoptosis by acting as a pro-apoptotic ligand. The apoptosis of cardiac myocytes induced by hypoxia/reoxygenation or ultraviolet irradiation was suppressed by anti-eIF5A neutralizing monoclonal antibodies (mAbs) in vitro. Myocardial ischemia/reperfusion (but not ischemia alone) markedly increased the plasma levels of eIF5A, and treatment with anti-eIF5A neutralizing mAbs significantly reduced myocardial injury. These results identify an important, novel specific biomarker and a critical therapeutic target for oxidative stress-indu...Continue Reading

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Citations

Apr 12, 2016·Chemico-biological Interactions·Cristina Hartmann-Fatu, Peter Bayer
Apr 4, 2017·Chemistry : a European Journal·Jan ReutzelArmin Geyer
Jul 12, 2017·Expert Review of Proteomics·Laura Mourino-AlvarezMaria G Barderas
May 8, 2019·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Yuta SuzukiShigehiko Kitano
May 6, 2020·Amino Acids·Annette KaiserJames Thujon Njuguna

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Methods Mentioned

BETA
electrophoresis
electron microscopy
surface plasmon resonance
enzyme-linked immunosorbent assay
PCR
Transfection
gel filtration
biosensor
chip

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