Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in cerebral ischemia/reperfusion injury
| Autor: | Ryu Ueno, Nobutaka Kawahara, Ko Okumura, Kota Araki, Tsutomu Fujimura, Kimie Murayama, Hajime Takase, Yoshinori Seko, Masao Kishimoto, Takashi Yamamoto, Nobuyuki Shimizu, Takako Yao, Jun Suenaga |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Ischemia lcsh:Medicine Apoptosis Pharmacology medicine.disease_cause Article Brain Ischemia Pathogenesis 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid Peptide Initiation Factors Rats Inbred SHR medicine Animals lcsh:Science Neurons Multidisciplinary business.industry Cerebral infarction lcsh:R Neuro-vascular interactions RNA-Binding Proteins Infarction Middle Cerebral Artery Hypoxia (medical) medicine.disease Cell Hypoxia Rats Stroke Oxidative Stress Reperfusion Injury 030220 oncology & carcinogenesis lcsh:Q medicine.symptom Apoptosis Regulatory Proteins business Reperfusion injury 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Oxidative stress is known to play a critical role in the pathogenesis of various disorders, especially in ischemia/reperfusion (I/R) injury. We identified an apoptosis-inducing humoral factor and named this novel post translationally modified secreted form of eukaryotic translation initiation factor 5A (eIF5A) “oxidative stress-responsive apoptosis inducing protein” (ORAIP). The purpose of this study was to investigate the role of ORAIP in the mechanisms of cerebral I/R injury. Hypoxia/reoxygenation induced expression of ORAIP in cultured rat cerebral neurons, resulting in extensive apoptosis of these cells, which was largely suppressed by neutralizing anti-ORAIP monoclonal antibody (mAb) in vitro. Recombinant-ORAIP induced extensive apoptosis of cerebral neurons. Cerebral I/R induced expression of ORAIP in many neurons in a rat tandem occlusion model in vivo. In addition, we analyzed the effects of intracerebroventricular administration of neutralizing anti-ORAIP mAb on the development of cerebral infarction. Cerebral I/R significantly increased ORAIP levels in cerebrospinal fluid. Treatment with intracerebroventricular administration of neutralizing anti-ORAIP mAb reduced infarct volume by 72%, and by 55% even when started after reperfusion. These data strongly suggest that ORAIP plays a pivotal role and will offer a critical therapeutic target for cerebral I/R injury induced by thrombolysis and thrombectomy for acute ischemic stroke. |
| Databáze: | OpenAIRE |
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