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Sci Rep. 2015 Sep 8;5:13737. doi: 10.1038/srep13737.

Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis.

Author information

1
Department of Cardiovascular Medicine, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6 Nihonbashi-Bakurocho, Chuo-ku, Tokyo 103-0002, Japan.
2
Department of Immunology, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan.
3
Division of Proteomics and Biomolecular Science, BioMedical Research Center, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan.

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-induced cell injury.

PMID:
26348594
PMCID:
PMC4562266
DOI:
10.1038/srep13737
[Indexed for MEDLINE]
Free PMC Article

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