Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis

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 myocyt...

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Main Authors:	Seko, Yoshinori, Fujimura, Tsutomu, Yao, Takako, Taka, Hikari, Mineki, Reiko, Okumura, Ko, Murayama, Kimie
Format:	Online
Language:	English
Published:	Nature Publishing Group 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562266/

id	pubmed-4562266
recordtype	oai_dc
spelling	pubmed-45622662015-09-15 Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis Seko, Yoshinori Fujimura, Tsutomu Yao, Takako Taka, Hikari Mineki, Reiko Okumura, Ko Murayama, Kimie Article 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. Nature Publishing Group 2015-09-08 /pmc/articles/PMC4562266/ /pubmed/26348594 http://dx.doi.org/10.1038/srep13737 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Seko, Yoshinori Fujimura, Tsutomu Yao, Takako Taka, Hikari Mineki, Reiko Okumura, Ko Murayama, Kimie
spellingShingle	Seko, Yoshinori Fujimura, Tsutomu Yao, Takako Taka, Hikari Mineki, Reiko Okumura, Ko Murayama, Kimie Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis
author_facet	Seko, Yoshinori Fujimura, Tsutomu Yao, Takako Taka, Hikari Mineki, Reiko Okumura, Ko Murayama, Kimie
author_sort	Seko, Yoshinori
title	Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis
title_short	Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis
title_full	Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis
title_fullStr	Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis
title_full_unstemmed	Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis
title_sort	secreted tyrosine sulfated-eif5a mediates oxidative stress-induced apoptosis
description	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.
publisher	Nature Publishing Group
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562266/
_version_	1613473476816928768

Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis

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