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Seko. Vessel Plus 2020;4:22 Vessel Plus
DOI: 10.20517/2574-1209.2020.14

Review Open Access

A novel and dominant factor that mediates oxidative
stress-induced apoptotic signaling - autocrine/

paracrine mechanism of the secreted form of
eukaryotic translation initiation factor 5A

Yoshinori Seko
Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Bunkyo-ku, Tokyo 113-8421, Japan.

Correspondence to: Dr. Yoshinori Seko, Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo
University, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: sekoyosh-tky@umin.ac.jp

How to cite this article: Seko Y. A novel and dominant factor that mediates oxidative stress-induced apoptotic signaling -
autocrine/paracrine mechanism of the secreted form of eukaryotic translation initiation factor 5A. Vessel Plus 2020;4:22.
http://dx.doi.org/10.20517/2574-1209.2020.14
Received: 6 May 2020 First Decision: 29 Jun 2020 Revised: 7 Jul 2020 Accepted: 15 Jul 2020 Published: 26 Jul 2020

Academic Editor: Cristina Vassalle Copy Editor: Cai-Hong Wang Production Editor: Jing Yu
Received: First Decision: Revised: Accepted: Published: x

Science Editor: Copy Editor: Production Editor: Jing Yu Abstract
Oxidative stress plays a critical role in the pathogenesis of various disorders including cardiovascular diseases,
such as ischemia/reperfusion (I/R) injury, atherosclerosis, dyslipidemia, chronic kidney disease (CKD),
arrhythmia, and diabetic cardiovascular complications. Although reactive oxygen species (ROS) have been
proposed as the key mediator of oxidative stress-induced cell injury, antioxidant therapies have failed in clinical
trials, raising the possibility that some unknown mechanism other than ROS may be involved. In 2015, we reported
a novel apoptosis-inducing humoral factor in conditioned medium from cardiac myocytes subjected to hypoxia/
reoxygenation. This novel 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A) was rapidly
secreted from cells in response to oxidative stress and then acted as an apoptosis-inducing ligand in an autocrine
fashion. We termed the novel secreted form of eIF5A “Oxidative stress-Responsive Apoptosis-Inducing Protein”
(ORAIP). Evidence has accumulated that ORAIP may be a common and dominant apoptosis-inducer among
various cell types in response to different types of oxidative stress and is involved in a wide spectrum of acute and
chronic disorders. Among them, here, I summarize knowledge regarding the possible roles of ORAIP in myocardial
and cerebral I/R injury, dyslipidemia in terms of atherosclerosis, cardiovascular complications in diabetes mellitus,
and CKD.

Keywords: Atherosclerosis, chronic kidney disease, diabetes mellitus, eukaryotic translation initiation factor 5A,

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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