Cargando…
Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells
We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755494/ https://www.ncbi.nlm.nih.gov/pubmed/29057797 http://dx.doi.org/10.3390/cells6040035 |
_version_ | 1783290595014344704 |
---|---|
author | Yao, Takako Fujimura, Tsutomu Murayama, Kimie Okumura, Ko Seko, Yoshinori |
author_facet | Yao, Takako Fujimura, Tsutomu Murayama, Kimie Okumura, Ko Seko, Yoshinori |
author_sort | Yao, Takako |
collection | PubMed |
description | We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to investigate the mechanism of cell injury of cardiac myocytes and pancreatic β-cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis in pancreatic β-cells. Plasma ORAIP levels in DM rats during diabetic phase were about 18 times elevated as compared with non-diabetic phase. High glucose induced massive apoptosis in cardiac myocytes (66.2 ± 2.2%), which was 78% suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant-ORAIP clearly induced apoptosis in pancreatic β-cells in vitro. These findings strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced myocardial injury and pancreatic β-cell injury in DM. ORAIP will be a biomarker and a critical therapeutic target for cardiac injury and progression of DM itself. |
format | Online Article Text |
id | pubmed-5755494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57554942018-01-07 Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells Yao, Takako Fujimura, Tsutomu Murayama, Kimie Okumura, Ko Seko, Yoshinori Cells Article We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo. In this study, to investigate the mechanism of cell injury of cardiac myocytes and pancreatic β-cells involved in diabetes mellitus (DM), we analyzed plasma ORAIP levels in DM model rats and the role of ORAIP in high glucose-induced apoptosis of cardiac myocytes in vitro. We also examined whether recombinant-ORAIP induces apoptosis in pancreatic β-cells. Plasma ORAIP levels in DM rats during diabetic phase were about 18 times elevated as compared with non-diabetic phase. High glucose induced massive apoptosis in cardiac myocytes (66.2 ± 2.2%), which was 78% suppressed by neutralizing anti-ORAIP mAb in vitro. Furthermore, recombinant-ORAIP clearly induced apoptosis in pancreatic β-cells in vitro. These findings strongly suggested that ORAIP plays a pivotal role in hyperglycemia-induced myocardial injury and pancreatic β-cell injury in DM. ORAIP will be a biomarker and a critical therapeutic target for cardiac injury and progression of DM itself. MDPI 2017-10-18 /pmc/articles/PMC5755494/ /pubmed/29057797 http://dx.doi.org/10.3390/cells6040035 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yao, Takako Fujimura, Tsutomu Murayama, Kimie Okumura, Ko Seko, Yoshinori Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells |
title | Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells |
title_full | Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells |
title_fullStr | Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells |
title_full_unstemmed | Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells |
title_short | Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in High Glucose-Induced Apoptosis in Rat Cardiac Myocytes and Murine Pancreatic β-Cells |
title_sort | oxidative stress-responsive apoptosis inducing protein (oraip) plays a critical role in high glucose-induced apoptosis in rat cardiac myocytes and murine pancreatic β-cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755494/ https://www.ncbi.nlm.nih.gov/pubmed/29057797 http://dx.doi.org/10.3390/cells6040035 |
work_keys_str_mv | AT yaotakako oxidativestressresponsiveapoptosisinducingproteinoraipplaysacriticalroleinhighglucoseinducedapoptosisinratcardiacmyocytesandmurinepancreaticbcells AT fujimuratsutomu oxidativestressresponsiveapoptosisinducingproteinoraipplaysacriticalroleinhighglucoseinducedapoptosisinratcardiacmyocytesandmurinepancreaticbcells AT murayamakimie oxidativestressresponsiveapoptosisinducingproteinoraipplaysacriticalroleinhighglucoseinducedapoptosisinratcardiacmyocytesandmurinepancreaticbcells AT okumurako oxidativestressresponsiveapoptosisinducingproteinoraipplaysacriticalroleinhighglucoseinducedapoptosisinratcardiacmyocytesandmurinepancreaticbcells AT sekoyoshinori oxidativestressresponsiveapoptosisinducingproteinoraipplaysacriticalroleinhighglucoseinducedapoptosisinratcardiacmyocytesandmurinepancreaticbcells |