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Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis.

Seko Y, Fujimura T, Yao T, Taka H, Mineki R, Okumura K, Murayama K - Sci Rep (2015)

Bottom Line: It causes cell damage that leads to apoptosis via uncertain mechanisms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6 Nihonbashi-Bakurocho, Chuo-ku, Tokyo 103-0002, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

A model for the mechanism by which oxidative stress induces apoptosis via the autocrine secretion of eIF5A (proposed based on the data obtained in the present study).AIF, apoptosis-inducing factor; cyt c, cytochrome c; dH, deoxyhypusine; DHS, deoxyhypusine synthase; DOHH, deoxyhypusine hydroxylase; H, hypusine; Jaks, Janus kinases; S, sulfated; PARP-1, poly (ADP-ribose) polymerase-1; STATs, signal transducers and activators of transcriptions; TPST, tyrosylprotein sulfotransferase.
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f6: A model for the mechanism by which oxidative stress induces apoptosis via the autocrine secretion of eIF5A (proposed based on the data obtained in the present study).AIF, apoptosis-inducing factor; cyt c, cytochrome c; dH, deoxyhypusine; DHS, deoxyhypusine synthase; DOHH, deoxyhypusine hydroxylase; H, hypusine; Jaks, Janus kinases; S, sulfated; PARP-1, poly (ADP-ribose) polymerase-1; STATs, signal transducers and activators of transcriptions; TPST, tyrosylprotein sulfotransferase.

Mentions: Hypusination may play an important role in receptor binding or signaling (Fig. 6). This hypothesis is supported by the known structural characteristics of eIF5A34. We posit that the extracellular function of eIF5A as a pro-apoptotic ligand may be the major function of this unique protein. Because eIF5A is ubiquitously and abundantly expressed in various cell types, this autocrine mechanism may mediate a common cellular response to oxidative stress. Here, we propose referring to this tyrosine-sulfated and hypusinated form of secreted eIF5A as Oxidative stress-Responsive Apoptosis Inducing Protein (ORAIP). The present study provides a novel specific biomarker and a potential therapeutic target for oxidative stress-induced cell injury.


Secreted tyrosine sulfated-eIF5A mediates oxidative stress-induced apoptosis.

Seko Y, Fujimura T, Yao T, Taka H, Mineki R, Okumura K, Murayama K - Sci Rep (2015)

A model for the mechanism by which oxidative stress induces apoptosis via the autocrine secretion of eIF5A (proposed based on the data obtained in the present study).AIF, apoptosis-inducing factor; cyt c, cytochrome c; dH, deoxyhypusine; DHS, deoxyhypusine synthase; DOHH, deoxyhypusine hydroxylase; H, hypusine; Jaks, Janus kinases; S, sulfated; PARP-1, poly (ADP-ribose) polymerase-1; STATs, signal transducers and activators of transcriptions; TPST, tyrosylprotein sulfotransferase.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562266&req=5

f6: A model for the mechanism by which oxidative stress induces apoptosis via the autocrine secretion of eIF5A (proposed based on the data obtained in the present study).AIF, apoptosis-inducing factor; cyt c, cytochrome c; dH, deoxyhypusine; DHS, deoxyhypusine synthase; DOHH, deoxyhypusine hydroxylase; H, hypusine; Jaks, Janus kinases; S, sulfated; PARP-1, poly (ADP-ribose) polymerase-1; STATs, signal transducers and activators of transcriptions; TPST, tyrosylprotein sulfotransferase.
Mentions: Hypusination may play an important role in receptor binding or signaling (Fig. 6). This hypothesis is supported by the known structural characteristics of eIF5A34. We posit that the extracellular function of eIF5A as a pro-apoptotic ligand may be the major function of this unique protein. Because eIF5A is ubiquitously and abundantly expressed in various cell types, this autocrine mechanism may mediate a common cellular response to oxidative stress. Here, we propose referring to this tyrosine-sulfated and hypusinated form of secreted eIF5A as Oxidative stress-Responsive Apoptosis Inducing Protein (ORAIP). The present study provides a novel specific biomarker and a potential therapeutic target for oxidative stress-induced cell injury.

Bottom Line: It causes cell damage that leads to apoptosis via uncertain mechanisms.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Medicine, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6 Nihonbashi-Bakurocho, Chuo-ku, Tokyo 103-0002, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus