Reference - Detail
|Author||Seko Y, Fujimura T, Yao T, Taka H, Mineki R, Okumura K, Murayama K.|
|Title||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 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.
|MeSH||Animals Antibodies, Monoclonal / pharmacology Antibodies, Neutralizing / pharmacology Apoptosis* / genetics Disease Models, Animal Golgi Apparatus / metabolism Humans Hypoxia / metabolism Male Models, Biological Myocardial Reperfusion Injury / drug therapy Myocardial Reperfusion Injury / genetics Myocardial Reperfusion Injury / metabolism Myocardial Reperfusion Injury / pathology Myocytes, Cardiac / metabolism* Oxidative Stress* / genetics Oxygen / metabolism Peptide Fragments / chemistry Peptide Fragments / metabolism Peptide Initiation Factors / antagonists & inhibitors Peptide Initiation Factors / genetics Peptide Initiation Factors / metabolism* Protein Transport RNA-Binding Proteins / antagonists & inhibitors RNA-Binding Proteins / genetics RNA-Binding Proteins / metabolism* Rats Signal Transduction Tyrosine / metabolism* trans-Golgi Network / metabolism|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY|
|DNA material||eIF5A cDNA on pcDNA4/Myc-His vector (RDB13750) FLAG-His-eIF5A on pcDNA3.1 (RDB13751) FLAG-His-eIF5A(K50A) on pcDNA3.1 (unhypusinated form) (RDB13752).|