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Cells 2017, 6(4), 35; https://doi.org/10.3390/cells6040035

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

1
Division of Cardiovascular Medicine, Institute for Adult Diseases, Asahi Life Foundation, Tokyo 103-0002, Japan
2
Laboratory of Bioanalytical Chemistry, Tohoku Medical and Pharmaceutical University, Sendai 981-0905, Japan
3
Division of Proteomics and Biomolecular Science, BioMedical Research Center, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
4
Department of Biofunctional Microbiota, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
*
Author to whom correspondence should be addressed.
Received: 12 September 2017 / Revised: 13 October 2017 / Accepted: 15 October 2017 / Published: 18 October 2017
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Abstract

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. View Full-Text
Keywords: apoptosis; cardiac myocytes; diabetes mellitus (DM); high glucose; oxidative stress; oxidative stress-responsive apoptosis inducing protein (ORAIP); pancreatic β-cells apoptosis; cardiac myocytes; diabetes mellitus (DM); high glucose; oxidative stress; oxidative stress-responsive apoptosis inducing protein (ORAIP); pancreatic β-cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Yao, T.; Fujimura, T.; Murayama, K.; Okumura, K.; Seko, Y. 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. Cells 2017, 6, 35.

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